ThalassemiaPhase 2BEYONDNCT03342404
A Study to Determine the Efficacy and Safety of Luspatercept in Adults With Non Transfusion Dependent Beta (β)-Thalassemia
A Phase 2 study testing Luspatercept in people with Thalassemia, run by Celgene at 16 sites in 6 countries.
Trial summary
This is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in adults with non-transfusion dependent beta (β)-thalassemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thalassemia
- What is being tested?
- Luspatercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 145 participants
- Where
- 16 sitesin 6 countries
- Study dates
- 5 Feb 2018to 28 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must satisfy the following criteria to be enrolled in the study:
- Subjects must be ≥ 18 years of age at the time of signing the informed consent document (ICF).
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study visit schedule (eg, not scheduled to receive hematopoietic stem cell transplantation) and other protocol requirements.
- Subject must have documented diagnosis of β-thalassemia or hemoglobin E/ β-thalassemia. Concomitant alpha globin mutation and/or duplication are allowed.
- Subject must be non-transfusion dependent, defined as 0 to 5 units of RBCs received during the 24-week period prior to randomization. Note: 1 unit defined for this entry criterion as approximately 200 to 350 mL of transfused packed RBCs.
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- Subject must not be on a regular transfusion program and must be RBC transfusion-free for at least ≥ 8 weeks prior to randomization
- Subject must have mean baseline hemoglobin ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to randomization; hemoglobin values within 21 days post-transfusion will be excluded.
- Subject must have performance status: Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.
- A female of childbearing potential (FCBP) for this study is defined as a female who:
- 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). A FCBP participating in the study must:
- Have 2 negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence* from heterosexual contact.
- Either commit to true abstinence* from heterosexual contact (which must be reviewed on a monthly basis and source documented). If a FCBP engages in sexual activity that may result in a pregnancy, she must agree to use, and be able to comply during the study therapy (including dose interruptions), and for 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple dose pharmacokinetics [PK] data) after discontinuation of study therapy.
- 10. Male subjects must:
- Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately 5 times the mean terminal half-life of luspatercept based on multiple-dose PK data) following IP discontinuation, even if he has undergone a successful vasectomy
Who cannot join
- The presence of any of the following will exclude a subject from enrollment:
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Diagnosis of hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg,Hemoglobin H).
- Active hepatitis C (HCV) infection
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- Deep vein thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
- Subjects on chronic anticoagulant therapy are excluded, unless they stopped the treatment at least 28 days prior to randomization. Anticoagulant therapies for prophylaxis and for surgery or high-risk procedures as well as low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) and chronic aspirin are allowed before and during the study.
- Treatment with another investigational drug or device ≤ 28 days prior to randomization.
- Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
- Platelet count > 1000 x 109/L.
- Subjects on iron chelation therapy (ICT) at the time of ICF signature must have initiated the treatment with ICT at least 24 weeks before the predicted randomization date. ICT can be initiated at any time during treatment and should be used according to the label.
- Subject had Hydroxyurea and ESA treatment ≤ 24 weeks prior to randomization, and no prior gene therapy.
- Subject is pregnant or a lactating female.
- Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE) version 4.0 (current active minor version).
- Subject has major organ damage, including:
- Liver disease with alanine aminotransferase (ALT) > 3 x upper limit of normal (ULN) or history/evidence of cirrhosis, as well as presence of masses/tumor detected by ultrasound at screening.
- Heart disease, heart failure as classified by the New York Heart Association (NYHA) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction (MI) within 6 months of randomization.
- Severe lung disease, including pulmonary fibrosis or pulmonary hypertension, ie, ≥G3 NCI CTCAE version 4.0 (current active minor version).
- Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 (per Modification of Diet in Renal Disease [MDRD] formula).
- Subject has received chronic systemic glucocorticoids ≤ 12 weeks prior to randomization (physiologic replacement therapy for adrenal insufficiency is allowed).
- Major surgery ≤ 12 weeks prior to randomization (subjects must have completely recovered from any previous surgery prior to randomization).
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator Brochure).
- Subject has received immunosuppressants ≤ 28 days prior to randomization.
- History or current malignancies (solid tumors and hematological malignancies) unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
Trial locations and contacts
16 sites in 6 countries.
16 sites in 6 countries
Italy7 sites
Local Institution - 205
Cagliari, 09121
Universita degli Studi di Cagliari - ASL8
Cagliari, 09121
Local Institution - 202
Genoa, 16128
Local Institution - 201
Milan, 20122
Local Institution - 203
Naples, 80131
Local Institution - 206
Naples, 80131
Local Institution - 204
Orbassano, 10043
United States4 sites
Local Institution - 503
Chicago, Illinois, 60611
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Local Institution - 501
Los Angeles, California, 90027
Children's Hospital and Research Center at Oakland
Oakland, California, 94609
Greece2 sites
Local Institution - 102
Athens, 115 27
Local Institution - 101
Athens, 11527
United Kingdom1 site
Local Institution - 601
London Bloomsbury, WC1E 6AU
About this study
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo in Adults With Non-Transfusion Dependent Beta (β)-Thalassemia (The BEYOND™ Study)
This is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in adults with non-transfusion dependent beta (β)-thalassemia. The study is divided into the Screening Period, Double-blind Treatment Period (DBTP), Open-label Phase (OLP), and Post-Treatment Follow-up Period (PTFP).
It is planned to randomize approximately 150 subjects at a 2:1 ratio of luspatercept versus placebo.
Read the detailed description
The primary objective is:
- To evaluate the effect of luspatercept (BMS-986346) versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval, from Week 13 to Week 24, compared to baseline.
The secondary objectives are:
- To evaluate the effect of luspatercept versus placebo in anemia-related symptoms in participants with β-thalassemia, as measured by non-transfusion dependent β-thalassemia-patient reported outcome (NTDT-PRO) over continuous 12-week intervals (from Weeks 13 to 24 and from Weeks 37 to 48) compared to baseline.
- To evaluate the effect of luspatercept versus placebo on functional and health-related quality of life (QoL) as measured by Medical Outcomes Study 36-Item Short Form (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires
- To evaluate the long-term effect of luspatercept versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval from Week 37 to Week 48, compared to baseline
- To evaluate the effect of luspatercept versus placebo on iron overload, as measured by liver iron concentration (LIC) and iron chelation therapy (ICT) daily dose
- To evaluate the effect of luspatercept versus placebo on iron overload, as measured by serum ferritin
- To evaluate the duration of erythroid response
- To evaluate the effect of luspatercept versus placebo on physical activity measured by 6-minute walk test (6MWT)
Safety and Pharmacokinetics (PK) Objectives
- To evaluate safety and tolerability of luspatercept, including immunogenicity
- To evaluate population pharmacokinetics (PK) of luspatercept in subjects with β-thalassemia
The exploratory objectives are:
- To evaluate the effect of luspatercept versus placebo on measures of extra-medullary hematopoietic (EMH) masses, bone mineral density, splenomegaly, pulmonary hypertension, and leg ulcers, when present
- To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the NTDT severity score system
- To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the Morbidity-free Survival parameters
- To examine the relationship of baseline and change in serum Growth Differentiation Factor 11 (GDF11) and other related biomarkers with response to treatment with luspatercept
- To examine the effect of luspatercept on fetal hemoglobin (HbF)
- To examine the effect of luspatercept on Health Resource Utilization (HRU)
- Conditions
- Thalassemia
- Being tested
- Luspatercept, Placebo, Best Supportive Care (BSC)
- Keywords
- (β)-Thalassemia, Beta-Thalassemia, Phase 2, Luspatercept, ACE-536, Safety, Efficacy, Placebo, Red Blood Cell Transfusions, Erythrocyte transfusion, Hb increase, NTDT
- Medical subject headings
- Thalassemia, beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LuspaterceptDrug
Also called ACE-536
Subjects will start with luspatercept at 1 mg/kg dose level every 3 weeks and can be dose escalated up to 1.25 mg/kg.
PlaceboOther
Also called normal saline
Placebo, Subcutaneous, every 21 days
Best Supportive Care (BSC)Other
Best Supportive Care (BSC)
| Study group | Role | What they receive |
|---|---|---|
| Luspatercept (ACE-536) plus Best Supportive Care (BSC) | Experimental | Arm Description: Luspatercept, subcutaneous(ly) (SC) once every 21 days Receives: Drug: Luspatercept; Other: Best Supportive Care (BSC) |
| Placebo plus Best Supportive Care (BSC) | Placebo comparator | normal saline solution subcutaneous(ly) (SC) once every 21 days Receives: Other: Placebo; Other: Best Supportive Care (BSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Erythroid Response (Week 13 to Week 24)
Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 13 to 24 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1.
Measured: From Week 13 to Week 24 of study treatment
Secondary outcomes (29)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 13 to Week 24)
The NTDT-PRO assesses the severity of anemia-related symptoms with a daily recall of symptoms composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score is the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores are the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 13 to Week 24) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13.
Measured: Baseline and over a continuous 12 week period (from week 13 through week 24)
Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 13 to Week 24)
Mean change from baseline in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 13 to Week 24 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1.
Measured: Baseline and over a continuous 12 week period (from week 13 through week 24)
Percentage of Participants Achieving Erythroid Response (Week 37 to Week 48)
Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 37 to 48 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1.
Measured: Assessed over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)
The FACIT-F is a multidimensional, self-report quality of life instrument which includes the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire (27 items over 4 different domains), and the Fatigue subscale (FS) component (13 items). FACIT-F version 4 has been used for this study. For the Fatigue subscale, each of the 13 items is scored from 0 ("not at all") to 4 ("very much"). The scores from individual items are summed to generated the final FS score, which ranges from 0 (best outcome) to 52 (worst outcome). The questionnaire is completed every other dose, and the mean of FS scores from Week 13 to Week 24 is compared to the FS score at baseline (last score available before start of study treatment). Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13.
Measured: Baseline and over a continuous 12 week period (from week 13 through week 24)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 13 to Week 24)
The NTDT-PRO V2.1 assess the severity of anemia-related symptoms associated with NTD β-thalassemia. It is a daily electronic diary with recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness (lack of energy) when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness (lack of strength) when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Shortness of Breath (SoB) domain score represents the average score of items 5 and 6 above. SoB domain score ranges from 0 (best outcome, no shortness of breath) to 10 (worst outcome, extreme shortness of breath). Weekly SoB Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12 week period (from Week 13 to Week 24) are compared to the SoB Domain Score at baseline.
Measured: Baseline and over a continuous 12 week period (from week 13 through week 24)
Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 37 to Week 48)
Mean change from baseline in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 37 to Week 48 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1.
Measured: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)
The FACIT-F is a multidimensional, self-report quality of life instrument which includes the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire (27 items over 4 different domains), and the Fatigue subscale (FS) component (13 items). FACIT-F version 4 has been used for this study. For the Fatigue subscale, each of the 13 items is scored from 0 ("not at all") to 4 ("very much"). The scores from individual items are summed to generated the final FS score, which ranges from 0 (best outcome) to 52 (worst outcome). The questionnaire is completed every other dose, and the mean of FS scores from Week 37 to Week 48 is compared to the FS score at baseline (last score available before start of study treatment). Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37.
Measured: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 37 to Week 48)
NTDT-PRO V2.1 assess the severity of anemia-related symptoms. It's a daily recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Tiredness/Weakness (T/W) domain score represents the average score of items 1 through 4 above. T/W domain score ranges from 0 (best outcome, no tiredness/weakness) to 10 (worst outcome, extreme tiredness/weakness). Weekly T/W Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 37 to Week 48) are compared to the T/W Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37.
Measured: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 37 to Week 48)
NTDT-PRO V2.1 assess the severity of anemia-related symptoms. It is a daily recall of symptoms during the past 24 hours, composed of 6 items: 1. Tiredness (lack of energy) when not doing physical activity 2. Tiredness when doing physical activity 3. Weakness (lack of strength) when not doing physical activity 4. Weakness when doing physical activity 5. Shortness of breath when not doing physical activity 6. Shortness of breath when doing physical activity. The Shortness of Breath (SoB) domain score represents the average score of items 5 and 6 above. SoB domain score ranges from 0 (best outcome, no shortness of breath) to 10 (worst outcome, extreme shortness of breath). Weekly SoB Scores represent the average of daily scores for that week. The mean of weekly scores over a continuous 12-week period (from Week 37 to Week 48) are compared to the SoB Domain Score at baseline. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37.
Measured: Baseline and over a continuous 12 week period (from week 37 through week 48)
Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)
The FACIT-Fatigue, is a multidimensional, self-report quality of life instrument. It consists of 27 core items, the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by a 13-item measure designed to capture cancer-related fatigue, the Fatigue subscale (FS). The items are measured on a response scale with five options (0 = not at all to 4 = very much). Participants completed the questionnaire at screening and every other dose. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 13. Score is calculated by multiplying the sum of item scores by the n of items in the scale, then divided by n of items answered.
Measured: Baseline and over a continuous 12 week period (from week 13 through week 24)
Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)
The FACIT-Fatigue, is a multidimensional, self-report quality of life instrument. It consists of 27 core items, the Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire, which assesses patient function in 4 domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by a 13-item measure designed to capture cancer-related fatigue, the Fatigue subscale (FS). The items are measured on a response scale with five options (0 = not at all to 4 = very much). Participants completed the questionnaire at screening and every other dose. Baseline is defined as the last value taken on or before the first dose of study drug administered in Week 37. Score is calculated by multiplying the sum of item scores by the n of items in the scale, then divided by n of items answered.
Measured: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in the Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of the Medical Outcomes Study 36-Item Short Form (SF-36)
The SF-36v2 is a 36-item generic PRO questionnaire used to assess patient-reported outcomes. The SF-36 yields scores for 8 domains of health: Physical Functioning (PF), Role-Physical (RP), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Functioning (SF), Role Emotional (RE), and Mental Health (MH) as well as physical component summary (PCS) and mental component summary (MCS) scores. Scores from each of the 8 domains of health are first normalized based on US general population means, then aggregated and transformed so that the scores from each of the 8 domains of health will contribute differently to the determination of PCS and MCS summary scores. PCS and MCS scores range from 0 to 100, with higher scores indicating a better quality of life. Baseline is defined as the last value taken on or before the first dose of study drug administered.
Measured: From baseline to Week 24 and from baseline to Week 48 of study treatment
Percentage of Participants With Improvement of Iron Overload
Iron overload was measured by Liver Iron Concentration (LIC) and Iron Chelation Therapy (ICT) daily dose. Improvement is defined as: - For participants with baseline LIC ≥3 mg/g: ≥20% reduction in LIC or ≥ 33% decrease in ICT daily dose - For participants with baseline LIC <3 mg/g: no increase in LIC >1 mg/g and not starting treatment with ICT, or no increase in ICT daily dose ≥ 33% (if on ICT at baseline)
Measured: Week 24 and Week 48 of study treatment
Mean Change From Baseline in Serum Ferritin
Baseline mean serum ferritin is calculated during the 24 weeks on or prior to dose 1 day 1. Post-baseline mean serum ferritin is calculated as mean of ferritin values during the last 24 weeks on or prior to the end date of the first 24 week or 48 week treatment
Measured: Week 24 and Week 48 of study treatment
Mean Change From Baseline in Liver Iron Concentration (LIC)
LIC was measured by Magnetic Resonance Imaging (MRI). Baseline is defined as the last value on or before the first dose of study drug is administered; Postbaseline is defined as the closest visit at Week 24 or Week 48. Participants with LIC value >43 are not included in the analysis.
Measured: Week 24 and Week 48 of study treatment
Percentage of Participants Who Are Transfusion-Free Over 24 Weeks
Transfusion free is defined as the absence of any transfusion during Week 1-24 of study treatment. Participants who discontinued treatment prior to Week 24 were not considered as transfusion free during Week 1-24.
Measured: From first dose to Week 24
Percentage of Participants Who Are Transfusion-Free Over 48 Weeks
Transfusion free is defined as the absence of any transfusion during Week 1-48 of study treatment. Participants who discontinued treatment prior to Week 48 were not considered as transfusion free during Week 1-48.
Measured: From first dose to Week 48
Duration of the Mean Hemoglobin Increase From Baseline ≥1.0 g/dL
This outcome measure is the cumulative mean of the duration of hemoglobin response for the ≥ 1.0 g/dL during any 12-week rolling period. Any hemoglobin values within 21 days after a transfusion were excluded from the analysis.
Measured: From baseline up to approximately 56 months
Mean Change From Baseline in the 6-Minute Walk Test (6MWT) Distance
The 6MWT is typically used to objectively assess functional exercise capacity and response to medical interventions in patients with various moderate to severe diseases. Particiapnts are asked to walk as quickly as possible without running along a 30-meter corridor for six minutes, and the total distance covered during that time is measured. Baseline is defined as the last value on or before the first dose of study drug is administered. Postbaseline is defined as the closest visit at Week 24 or Week 48.
Measured: From baseline to Week 24 and from baseline to Week 48 of study treatment
Percentage of Participants With an Increase From Baseline ≥1.5 g/dL in Mean Hemoglobin Values in the Absence of Transfusion
Percentage of participants who have an increase from baseline ≥1.5 g/dL in mean of hemoglobin (Hb) values over a continuous 12-week interval from Week 13 to Week 24 in the absence of transfusions. Baseline was defined as the average of 2 or more Hb measurements at least 1 week apart within 4 weeks before Dose 1 Day 1.
Measured: From Week 13 to Week 24 of study treatment
Percentage of Participants With a Decrease From Baseline ≥ RD (= 1) in the Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score
The responder definition (RD) threshold is the individual participant score change over a predetermined time period that will be interpreted as a treatment benefit. The RD for the NTDT-PRO T/W domain score was defined as ≥ 1-point decrease (ie, RD = -1) from baseline over the time from Week 13 to Week 24 or from Week 37 to Week 48. Participants with missing NTDT-PRO T/W scores at the indicated 12-week period are classified as non-responders in the analysis.
Measured: From Week 13 to Week 24 and from Week 37 to Week 48 of study treatment
Number of Participants Experiencing Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Adverse events are graded on a scale from 1 to 5, with Grade 1 being mild and asymptomatic; Grade 2 is moderate requiring minimal, local or noninvasive intervention; Grade 3 is severe or medically significant but not immediately life-threatening; Grade 4 events are usually severe enough to require hospitalization; Grade 5 events are fatal.
Measured: From first dose to 63 days after last dose (up to approximately 56 months)
Number of Participants With Anti-drug Antibody (ADA) Positive Test for Luspatercept
Presence of anti-drug (ACE-536/Luspatercept) antibodies was assessed every 24 weeks from serum samples. A participant is counted as 'positive' if there is any positive result captured during the study.
Measured: From first dose and up to 2 years following last dose, up to approximately 56 months
Apparent Clearance (CL/F) of Luspatercept
Apparent Clearance (CL/F) of Luspatercept
Measured: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Apparent Volume of Distribution of the Central Compartment (V1/F) of Luspatercept
Apparent Volume of Distribution of the Central Compartment (V1/F) of Luspatercept
Measured: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Time to Reach Maximum Concentration (Tmax) of Luspatercept
Time to Reach Maximum Concentration (Tmax) of Luspatercept
Measured: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Maximum Concentration (Cmax) of Luspatercept
Maximum Concentration (Cmax) of Luspatercept
Measured: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Maximum Concentration From Steady State (Cmax,ss) of Luspatercept
Maximum Concentration From Steady State (Cmax,ss) of Luspatercept
Measured: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Area Under the Curve From Steady State (AUCss) of Luspatercept
Area Under the Curve From Steady State (AUCss) of Luspatercept
Measured: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start5 Feb 2018
- Primary completion28 Nov 2022
- Study completion28 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Responsible party
- Sponsor
- Investigators
- Jeevan Shetty, MD, Study director, Celgene Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03342404
- Sponsor's protocol ID
- ACE-536-B-THAL-002
- Other IDs
- U1111-1202-7068, 2015-003225-33, 2015
- Acronym
- BEYOND
- Status last verified
- Nov 2023
- First submitted
- 30 Oct 2017
- Last updated
- 20 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.
PubMed 30617198Musallam KM, Cappellini MD, Kattamis A, Dyer M, Hnoosh A, Eliason L, Pelligra CG, Guo S, Mu Y, Medlin LF, Reverte M, Kuo KHM, Taher AT. Patient-Reported Outcomes With Luspatercept Through 5 Years of Treatment in Patients With Non-Transfusion-Dependent beta-Thalassemia Treated in the BEYOND Trial. Eur J Haematol. 2026 Jul;117(1):161-173. doi: 10.1111/ejh.70161. Epub 2026 Mar 19.
PubMed 41857682Taher AT, Viprakasit V, Kattamis A, Perrotta S, Ricchi P, Porter JB, Coates TD, Forni GL, Musallam KM, Esposito O, Pilot R, Kuo WL, Lai Y, Reverte M, Wei R, Bueno LM, Cappellini MD. Efficacy and safety of luspatercept in non-transfusion-dependent beta-thalassemia: long-term results from the BEYOND study. Blood Adv. 2025 Dec 9;9(23):6108-6119. doi: 10.1182/bloodadvances.2025016554.
PubMed 40875596Denton CC, Vodala S, Veluswamy S, Hofstra TC, Coates TD, Wood JC. Splenic iron decreases without change in volume or liver parameters during luspatercept therapy. Blood. 2023 Nov 30;142(22):1932-1934. doi: 10.1182/blood.2023021839.
PubMed 37704579Taher AT, Musallam KM, Viprakasit V, Kattamis A, Lord-Bessen J, Yucel A, Guo S, Pelligra C, Shields AL, Shetty JK, Miteva D, Bueno LM, Cappellini MD. Psychometric evaluation of the NTDT-PRO questionnaire for assessing symptoms in patients with non-transfusion-dependent beta-thalassaemia. BMJ Open. 2023 Mar 22;13(3):e066683. doi: 10.1136/bmjopen-2022-066683.
PubMed 36948565Taher AT, Cappellini MD, Kattamis A, Voskaridou E, Perrotta S, Piga AG, Filosa A, Porter JB, Coates TD, Forni GL, Thompson AA, Tartaglione I, Musallam KM, Backstrom JT, Esposito O, Giuseppi AC, Kuo WL, Miteva D, Lord-Bessen J, Yucel A, Zinger T, Shetty JK, Viprakasit V; BEYOND Investigators. Luspatercept for the treatment of anaemia in non-transfusion-dependent beta-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial. Lancet Haematol. 2022 Oct;9(10):e733-e744. doi: 10.1016/S2352-3026(22)00208-3. Epub 2022 Aug 22.
PubMed 36007538
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Double-Blind, Randomized, Placebo-Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) Versus Placebo in Adults With Non-Transfusion Dependent Beta (β)-Thalassemia (The BEYOND™ Study)
- ClinicalTrials.gov ID
- NCT03342404
- Acronym / sponsor ID
- BEYOND / ACE-536-B-THAL-002
- Conditions
- Thalassemia
- Keywords
- (β)-Thalassemia, Beta-Thalassemia, Phase 2, Luspatercept, ACE-536, Safety, Efficacy, Placebo
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Collaborators
- Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
- Study start
- 5 Feb 2018 (actual)
- Primary completion
- 28 Nov 2022 (actual)
- Study completion
- 28 Nov 2022 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Posted 18 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in adults with non-transfusion dependent beta (β)-thalassemia. The study is divided into the Screening Period, Double-blind Treatment Period (DBTP), Open-label Phase (OLP), and Post-Treatment Follow-up Period (PTFP).
It is planned to randomize approximately 150 subjects at a 2:1 ratio of luspatercept versus placebo.
Detailed description
The primary objective is:
- To evaluate the effect of luspatercept (BMS-986346) versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval, from Week 13 to Week 24, compared to baseline.
The secondary objectives are:
- To evaluate the effect of luspatercept versus placebo in anemia-related symptoms in participants with β-thalassemia, as measured by non-transfusion dependent β-thalassemia-patient reported outcome (NTDT-PRO) over continuous 12-week intervals (from Weeks 13 to 24 and from Weeks 37 to 48) compared to baseline.
- To evaluate the effect of luspatercept versus placebo on functional and health-related quality of life (QoL) as measured by Medical Outcomes Study 36-Item Short Form (SF-36) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires
- To evaluate the long-term effect of luspatercept versus placebo on anemia, as measured by mean hemoglobin concentration in the absence of transfusions over a continuous 12-week interval from Week 37 to Week 48, compared to baseline
- To evaluate the effect of luspatercept versus placebo on iron overload, as measured by liver iron concentration (LIC) and iron chelation therapy (ICT) daily dose
- To evaluate the effect of luspatercept versus placebo on iron overload, as measured by serum ferritin
- To evaluate the duration of erythroid response
- To evaluate the effect of luspatercept versus placebo on physical activity measured by 6-minute walk test (6MWT)
Safety and Pharmacokinetics (PK) Objectives
- To evaluate safety and tolerability of luspatercept, including immunogenicity
- To evaluate population pharmacokinetics (PK) of luspatercept in subjects with β-thalassemia
The exploratory objectives are:
- To evaluate the effect of luspatercept versus placebo on measures of extra-medullary hematopoietic (EMH) masses, bone mineral density, splenomegaly, pulmonary hypertension, and leg ulcers, when present
- To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the NTDT severity score system
- To evaluate the effect of luspatercept versus placebo on the β-thalassemia severity as measured by the Morbidity-free Survival parameters
- To examine the relationship of baseline and change in serum Growth Differentiation Factor 11 (GDF11) and other related biomarkers with response to treatment with luspatercept
- To examine the effect of luspatercept on fetal hemoglobin (HbF)
- To examine the effect of luspatercept on Health Resource Utilization (HRU)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Luspatercept (ACE-536) plus Best Supportive Care (BSC) | Experimental | Drug: Luspatercept, Other: Best Supportive Care (BSC)Arm Description: Luspatercept, subcutaneous(ly) (SC) once every 21 days |
| Placebo plus Best Supportive Care (BSC) | Placebo comparator | Other: Placebo, Other: Best Supportive Care (BSC)normal saline solution subcutaneous(ly) (SC) once every 21 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subjects must be ≥ 18 years of age at the time of signing the informed consent document (ICF).
- Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- Subject is willing and able to adhere to the study visit schedule (eg, not scheduled to receive hematopoietic stem cell transplantation) and other protocol requirements.
- Subject must have documented diagnosis of β-thalassemia or hemoglobin E/ β-thalassemia. Concomitant alpha globin mutation and/or duplication are allowed.
- Subject must be non-transfusion dependent, defined as 0 to 5 units of RBCs received during the 24-week period prior to randomization. Note: 1 unit defined for this entry criterion as approximately 200 to 350 mL of transfused packed RBCs.
Key exclusion criteria (29 listed)
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- Any condition that confounds the ability to interpret data from the study.
- Diagnosis of hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg,Hemoglobin H).
- Active hepatitis C (HCV) infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LuspaterceptAlso: ACE-536Subjects will start with luspatercept at 1 mg/kg dose level every 3 weeks and can be dose escalated up to 1.25 mg/kg. | Drug | Luspatercept (ACE-536) plus Best Supportive Care (BSC) |
| PlaceboAlso: normal salinePlacebo, Subcutaneous, every 21 days | Other | Placebo plus Best Supportive Care (BSC) |
| Best Supportive Care (BSC)Best Supportive Care (BSC) | Other | Luspatercept (ACE-536) plus Best Supportive Care (BSC), Placebo plus Best Supportive Care (BSC) |
Primary outcome
Percentage of Participants Achieving Erythroid Response (Week 13 to Week 24)
Time frame: From Week 13 to Week 24 of study treatment
Erythroid Response is defined as an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Weeks 13 to 24 of treatment in the absence of transfusions. Baseline hemoglobin (Hb) is the average of 2 or more Hb measurements at least 1 week apart within 4 weeks prior to Dose 1.
29 secondary outcomes
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 13 to Week 24)
Time frame: Baseline and over a continuous 12 week period (from week 13 through week 24)
Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 13 to Week 24)
Time frame: Baseline and over a continuous 12 week period (from week 13 through week 24)
Percentage of Participants Achieving Erythroid Response (Week 37 to Week 48)
Time frame: Assessed over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)
Time frame: Baseline and over a continuous 12 week period (from week 13 through week 24)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 13 to Week 24)
Time frame: Baseline and over a continuous 12 week period (from week 13 through week 24)
Mean Change From Baseline in Hemoglobin Values in the Absence of Transfusion (Week 37 to Week 48)
Time frame: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)
Time frame: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score (Week 37 to Week 48)
Time frame: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Shortness of Breath (SoB) Domain Score (Week 37 to Week 48)
Time frame: Baseline and over a continuous 12 week period (from week 37 through week 48)
Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 13 to Week 24)
Time frame: Baseline and over a continuous 12 week period (from week 13 through week 24)
Percentage of Participants With an Increase From Baseline ≥ 3 in Mean Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Fatigue Subscale Score (Week 37 to Week 48)
Time frame: Baseline and over a continuous 12 week period (from week 37 through week 48)
Mean Change From Baseline in the Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores of the Medical Outcomes Study 36-Item Short Form (SF-36)
Time frame: From baseline to Week 24 and from baseline to Week 48 of study treatment
Percentage of Participants With Improvement of Iron Overload
Time frame: Week 24 and Week 48 of study treatment
Mean Change From Baseline in Serum Ferritin
Time frame: Week 24 and Week 48 of study treatment
Mean Change From Baseline in Liver Iron Concentration (LIC)
Time frame: Week 24 and Week 48 of study treatment
Percentage of Participants Who Are Transfusion-Free Over 24 Weeks
Time frame: From first dose to Week 24
Percentage of Participants Who Are Transfusion-Free Over 48 Weeks
Time frame: From first dose to Week 48
Duration of the Mean Hemoglobin Increase From Baseline ≥1.0 g/dL
Time frame: From baseline up to approximately 56 months
Mean Change From Baseline in the 6-Minute Walk Test (6MWT) Distance
Time frame: From baseline to Week 24 and from baseline to Week 48 of study treatment
Percentage of Participants With an Increase From Baseline ≥1.5 g/dL in Mean Hemoglobin Values in the Absence of Transfusion
Time frame: From Week 13 to Week 24 of study treatment
Percentage of Participants With a Decrease From Baseline ≥ RD (= 1) in the Non-Transfusion Dependent β-thalassemia-Patient Reported Outcome (NTDT-PRO) Tiredness and Weakness (T/W) Domain Score
Time frame: From Week 13 to Week 24 and from Week 37 to Week 48 of study treatment
Number of Participants Experiencing Adverse Events
Time frame: From first dose to 63 days after last dose (up to approximately 56 months)
Number of Participants With Anti-drug Antibody (ADA) Positive Test for Luspatercept
Time frame: From first dose and up to 2 years following last dose, up to approximately 56 months
Apparent Clearance (CL/F) of Luspatercept
Time frame: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Apparent Volume of Distribution of the Central Compartment (V1/F) of Luspatercept
Time frame: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Time to Reach Maximum Concentration (Tmax) of Luspatercept
Time frame: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Maximum Concentration (Cmax) of Luspatercept
Time frame: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Maximum Concentration From Steady State (Cmax,ss) of Luspatercept
Time frame: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Area Under the Curve From Steady State (AUCss) of Luspatercept
Time frame: Doses 1 to 16: at predose (must be collected before first dose), Dose 2 Day 1, Dose 4 Day 1, Dose 6 Day 1, Dose 8 Day 1, Dose 12 Day 1, Dose 16 Day 1, Dose 6 Day 8, Dose 6 Day 15, and every 6 doses (at Dose 22, 28, etc.), up to approx. 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 30617198Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.
- Derived from this study: PubMed 41857682Musallam KM, Cappellini MD, Kattamis A, Dyer M, Hnoosh A, Eliason L, Pelligra CG, Guo S, Mu Y, Medlin LF, Reverte M, Kuo KHM, Taher AT. Patient-Reported Outcomes With Luspatercept Through 5 Years of Treatment in Patients With Non-Transfusion-Dependent beta-Thalassemia Treated in the BEYOND Trial. Eur J Haematol. 2026 Jul;117(1):161-173. doi: 10.1111/ejh.70161. Epub 2026 Mar 19.
- Derived from this study: PubMed 40875596Taher AT, Viprakasit V, Kattamis A, Perrotta S, Ricchi P, Porter JB, Coates TD, Forni GL, Musallam KM, Esposito O, Pilot R, Kuo WL, Lai Y, Reverte M, Wei R, Bueno LM, Cappellini MD. Efficacy and safety of luspatercept in non-transfusion-dependent beta-thalassemia: long-term results from the BEYOND study. Blood Adv. 2025 Dec 9;9(23):6108-6119. doi: 10.1182/bloodadvances.2025016554.
- Derived from this study: PubMed 37704579Denton CC, Vodala S, Veluswamy S, Hofstra TC, Coates TD, Wood JC. Splenic iron decreases without change in volume or liver parameters during luspatercept therapy. Blood. 2023 Nov 30;142(22):1932-1934. doi: 10.1182/blood.2023021839.
- Derived from this study: PubMed 36948565Taher AT, Musallam KM, Viprakasit V, Kattamis A, Lord-Bessen J, Yucel A, Guo S, Pelligra C, Shields AL, Shetty JK, Miteva D, Bueno LM, Cappellini MD. Psychometric evaluation of the NTDT-PRO questionnaire for assessing symptoms in patients with non-transfusion-dependent beta-thalassaemia. BMJ Open. 2023 Mar 22;13(3):e066683. doi: 10.1136/bmjopen-2022-066683.
- Derived from this study: PubMed 36007538Taher AT, Cappellini MD, Kattamis A, Voskaridou E, Perrotta S, Piga AG, Filosa A, Porter JB, Coates TD, Forni GL, Thompson AA, Tartaglione I, Musallam KM, Backstrom JT, Esposito O, Giuseppi AC, Kuo WL, Miteva D, Lord-Bessen J, Yucel A, Zinger T, Shetty JK, Viprakasit V; BEYOND Investigators. Luspatercept for the treatment of anaemia in non-transfusion-dependent beta-thalassaemia (BEYOND): a phase 2, randomised, double-blind, multicentre, placebo-controlled trial. Lancet Haematol. 2022 Oct;9(10):e733-e744. doi: 10.1016/S2352-3026(22)00208-3. Epub 2022 Aug 22.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeevan Shetty, MD study director
Celgene Corporation
16 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Luspatercept in people with Thalassemia, run by Celgene at 16 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Italy, United States, Greece, Lebanon, Thailand and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Erythroid Response (Week 13 to Week 24) (time frame: From Week 13 to Week 24 of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03342404, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2023.