AnemiaPhase 2NCT05664737
A Study to Determine the Efficacy and Safety of Luspatercept in Adult Participants and to Evaluate the Safety and Pharmacokinetics in and Adolescent Participants With Alpha (α)-Thalassemia
A Phase 2 study testing Luspatercept in people with Anemia, run by Bristol-Myers Squibb at 31 sites in 10 countries.
Trial summary
The purpose of the study is to evaluate the efficacy and safety of luspatercept plus best supportive care (BSC) vs placebo plus BSC on anemia in adult participants with α-thalassemia hemoglobin H (HbH) disease and determine the safety and drug levels in adolescent participants. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Anemia
- What is being tested?
- Luspatercept
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 189 participants
- Where
- 31 sitesin 10 countries
- Study dates
- 9 Dec 2022to 14 Aug 2034
- Phase
- Phase 2
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Adult participant≥ 18 years with documented diagnosis of A-Thal HbH disease with Transfusion dependence defined as:.
- TD participant: ≥ 6 RBC units during the 24 weeks prior to randomization. ii) NTD participant:< 6 RBC units during the 24 weeks prior to randomization(transfusion due to conditions other than A-Thal will not be considered)and, RBC transfusion-free during at least 8 weeks prior to randomization(unless transfusion was required to treat an acute medical condition other than A-Thal) and, mean baseline Hb ≤ 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.
- Adult participant has Eastern Cooperative Oncology Group (ECOG) 34 score of 0 or 1.
- Adolescent participant 12 years to < 18 years with documented diagnosis of A-Thal HbH disease with transfusion dependence defined as:.
- TD participant: ≥ 4 RBC events during the 24 weeks prior to enrollment and, no transfusion-free period for > 56 days during the 24 weeks prior to enrollment. Participants must have a history of regular transfusions for at least 2 years.
- NTD participant:< 4 RBC events during the 24 weeks prior to enrollment and RBC transfusion-free during at least 8 weeks prior to enrollment and, mean baseline Hb ≤ 10 g/dL, based on a minimum of 2 measurements ≥ 1 week apart within 4 weeks prior to enrollment, hemoglobin values within 21 days post-transfusion will be excluded.
- Participant has Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status score ≥ 50 at screening.
Who cannot join
- Medical Conditions: Diagnosis of A-ThalTrait, Hb Bart hydrops, ATRx A-Thal, hemoglobin S/β-thalassemia, myelodysplasia subtype anemia, or with HbE homozygous beta gene mutation. Anemia related to nutritional deficiency, anemia of chronic disease, autoimmune hemolytic anemia, or any other hemolytic anemias. Undergone episodes of hemolysis not related to A-Thal within the 8 weeks prior to randomization. Applicable for the EU only: Bleeding disorders manifested by frequent bleeding episodes (eg, menorrhagia, epistaxis, clotting disorders).
- Participant has deep vein thrombosis (DVT), stroke or other thromboembolic event(s) (except clogged indwelling catheter) requiring medical intervention ≤ 24weeks prior to randomization.
- Participant has uncontrolled hypertension. Controlled hypertension for this protocol is considered: blood pressure value corresponding to ≤Grade 1 according to NCI CTCAE Version 5.0. with or without pharmacological treatment.
- Reproductive Status: Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding.
- Prior/Concomitant: Undergone HSCTs or gene therapy (candidates for HSCT or gene therapy with waiting period of ≥ 12 months are eligible).
- Use of hydroxyurea treatment ≤ 12 weeks prior to enrollment for NTD participants and ≤ 24 weeks for TD participants.
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- Participant who has extramedullary hematopoiesis (EMH) complications requiring treatment to control the growth of EMH mass(es) during the screening period.
- Any medical or psychiatric condition (including active infections, recent surgery, sequelae of diseases or interventions, clinically significant laboratory abnormalities or concurrent treatment) that in the opinion of the investigator would put the participant at unacceptable risk of participating in the study or that could affect interpretability of data.
- Other protocol-defined inclusion/exclusion criteria apply.
Trial locations and contacts
31 sites in 10 countries.
31 sites in 10 countries
China11 sites
Local Institution - 0013
Foshan, Guangdong, 528000
Local Institution - 0029
Guangzhou, GD, 510120
Local Institution - 0015
Guangzhou, GD, 510515
Local Institution - 0011
Haikou, Hainan, 570203
Local Institution - 0002
Haikou, 570311
Local Institution - 0012
Kunming, Yunnan, 650032
Local Institution - 0023
Liuzhou, Guangxi, 545006
Local Institution - 0017
Maoming Shi, Guangdong, 525000
Local Institution - 0014
Nanning, GX, 530021
Local Institution - 0016
Nanning, 530021
Local Institution - 0030
Shenzhen Shi, Guangdong, 518025
Greece4 sites
Local Institution - 0006
Athens, 115 27
Local Institution - 0009
Goudi, 11527
Local Institution - 0007
Larissa, 26504
Local Institution - 0018
Rio, G, 265 04
Italy4 sites
Local Institution - 0026
Genova, GE, 16128
Local Institution - 0028
Naples, 80131
Local Institution - 0019
Naples, 80138
Local Institution - 0020
Orbassano, TO, 10043
Taiwan3 sites
Local Institution - 0010
Kaohsiung City, KHH, 807
Local Institution - 0004
Nan Gang Qu, TPE, 10002
Local Institution - 0003
Taichung, TXG, 40447
Malaysia2 sites
Local Institution - 0033
Johor Bahru, 80100
Local Institution - 0032
Kuala Lumpur, WP, 50586
Thailand2 sites
Local Institution - 0001
Bangkok Noi, Bangkok, 10700
Local Institution - 0031
Mueang Phitsanulok, 65000
Turkey (Türkiye)2 sites
Local Institution - 0027
Altındağ, 06230
Local Institution - 0021
Topkapı, 34093
About this study
Official title: A Phase 2, Study for the Treatment of Anemia With Alpha (α)-Thalassemia to Determine the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) in Adults and Evaluate the Safety and Pharmacokinetics in Adolescents
The purpose of the study is to evaluate the efficacy and safety of luspatercept plus best supportive care (BSC) vs placebo plus BSC on anemia in adult participants with α-thalassemia hemoglobin H (HbH) disease and determine the safety and drug levels in adolescent participants.
- Conditions
- Anemia
- Being tested
- Luspatercept, Placebo
- Keywords
- Luspatercept, BMS-986346, ACE-536, α-thalassemia, Alpha Thalassemia, Reblozyl, Transfusions, Non-transfusion dependent, RBC transfusion dependent
- Medical subject headings
- Anemia, alpha-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LuspaterceptBiological
Also called BMS-986346, ACE-536, REBLOZYL
Specified dose on specified days
PlaceboDrug
Specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Transfusion Dependent (TD): Luspatercept + Best supportive care (BSC) | Experimental | Not described Receives: Biological: Luspatercept |
| Adult TD Cohort: Placebo + BSC | Placebo comparator | Not described Receives: Drug: Placebo |
| Non-transfusion Dependent (NTD): Luspatercept + BSC | Experimental | Not described Receives: Biological: Luspatercept |
| Adult NTD Cohort: Placebo + BSC | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 12 weeks during Week 13-48 compared to 12-week interval immediately prior to date of first dose
Adult TD Cohort
Measured: Up to Week 48
Number of participants with an increase from baseline of ≥ 1.0 grams (g)/decilitre (dL) in mean hemoglobin (Hb) values over the continuous 12-week interval from Week 13 to Week 24 in the absence of RBC transfusion
Adult NTD Cohort
Measured: Up to Week 24
Dose-limiting toxicities (DLTs) defined as observance of ≥ Grade 3-related hemolytic crises or ≥ Grade 3-related event outside of the known safety profile occurring within the 21 days from their first dose of study therapy
Adolescent TD and NTD Cohorts
Measured: Up to Week 3
Number of participants with adverse events (AEs)
Adolescent TD and NTD Cohorts
Measured: Up to 5 years
Pharmacokinetics (PK): Serum concentration of Luspatercept
Adolescent TD and NTD Cohorts
Measured: Up to Week 108
Secondary outcomes (65)
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 24-week interval on treatment compared to 24-week interval immediately prior to date of first dose
Adult TD Cohort
Measured: Up to Week 108
The longest duration with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units
Adult TD Cohort
Measured: Up to Week 108
Number of RBC transfusion units from week 1 to week 48
Adult and Adolescent TD Cohorts
Measured: Up to Week 48
Change from baseline in hemoglobin in the absence of transfusion at Week 24
Adult and Adolescent NTD Cohorts
Measured: Up to Week 24
The longest duration of an increase from baseline of ≥ 1.0 g/dL in mean hemoglobin values starting from Week 13 in the absence of transfusion
Adult NTD Cohort
Measured: Up to Week 108
Time Duration with an increase from baseline of ≥ 1.0 g/dL in hemoglobin values in the absence of transfusion within 48 weeks
Adult NTD Cohort
Measured: Up to Week 48
Number of participants with an increase from baseline of ≥1.0 g/dL in mean Hb values over the continuous 12- week interval in the absence of transfusion
Adult NTD Cohort
Measured: Up to Week 24
≥ 3 Increase from Baseline in Functional Assessment of Cancer Therapy Anemia Fatigue Subscale (FACT-An FS) Score from Baseline to the period from Week 13 to Week 24
Adult NTD Cohort
Measured: Up to Week 24
Number of participants with AEs
Adult and Adolescent TD and NTD Cohorts
Measured: Up to 5 years
Number of participants with laboratory abnormalities
Adult TD and NTD Cohorts
Measured: Up to 5 Years
Number of participants with immunogenicity
Adult TD and NTD Cohorts
Measured: Up to 2 Years
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden during any continuous 24-week interval within 48 weeks compared to the 24-week interval immediately prior to the date of first dose
Adult TD Cohort
Measured: Up to Week 48
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden during any continuous 12-week interval compared to the 12-week interval immediately prior to the date of first dose
Adult TD Cohort
Measured: Up to Week 108
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden from Week 13 to Week 24 and Week 37 to Week 48 compared to the 12-week interval immediately prior to the date of first dose
Adult TD Cohort
Measured: Up to Week 48
Number of participants with ≥ 33% reduction from baseline in RBC transfusion burden from Week 1 to Week 24 and Week 25 to Week 48 compared to the 24-week interval immediately prior to the date of first dose
Adult TD Cohort
Measured: Up to Week 48
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden from Week 13 to Week 24 and Week 37 to Week 48 compared to the 12-week interval immediately prior to the date of first dose
Adult TD Cohort
Measured: Up to Week 48
Number of participants with ≥ 50% reduction from baseline in RBC transfusion burden from Week 1 to Week 24 and Week 25 to Week 48 compared to the 24-week interval immediately prior to the date of first dose
Adult TD Cohort
Measured: Up to Week 48
Change from baseline in total RBC units transfused from Week 1 to Week 24, Week 25 to Week 48, and Week 1 to Week 48
Adult TD Cohort
Measured: Up to Week 48
The longest duration of RBC transfusion-free period for participants who achieve transfusion-free period of ≥ 12 weeks
Adult TD Cohort
Measured: Up to Week 108
The longest duration of reduction in transfusion burden for participants who achieve a response (rolling 12-week and 24-week response, both for ≥ 33% and ≥ 50% reduction)
Adult TD Cohort
Measured: Up to Week 108
Time from first dose to first day of response (rolling 12-week and 24-week response, both for ≥ 33% and ≥ 50% reduction)
Adult TD Cohort
Measured: Up to Week 108
Change from baseline in number of transfusion events at Week 48
Adult TD Cohort
Measured: Up to Week 48
Number of participants who achieve RBC transfusion-free period of any continuous ≥ 12 weeks during treatment
Adult and Adolescent TD and NTD Cohorts
Measured: Up to Week 108
Number of participants who achieve RBC transfusion-free period of any continuous ≥ 24 weeks during treatment
Adult and Adolescent TD and NTD Cohorts
Measured: Up to Week 108
Time to first transfusion
Adult and Adolescent NTD Cohorts
Measured: Up to Week 108
Number of transfusions
Adult NTD Cohort
Measured: Within 48 Weeks
Number of transfusion visits/units
Adult NTD Cohort
Measured: Within 48 Weeks
Change from baseline in mean hemoglobin values over the continuous 12-week interval from Week 13 to Week 24 and Week 37 to Week 48 in the absence of transfusions
Adult TD and NTD Cohorts
Measured: Up to Week 48
Number of participants achieving an increase from baseline of ≥1.0g/dL or ≥1.5g/dL in mean Hb values in absence of transfusions from Week 13 to Week 24, Week 37 to Week 48 and during any continuous 12-week window within 24 weeks and 48 weeks
Adult NTD Cohort
Measured: Up to Week 48
Time from first to last Hb measurement with increase from baseline by ≥ 1.0 g/dL
Adult NTD Cohorts
Measured: Up to Week 108
Time to the first increase from baseline of ≥ 1.0 g/dL in mean Hb value
Adolescent NTD Cohort
Measured: Up to Week 48
Number of participants who achieve an increase in mean Hb of >10g/dL values during any continuous 12-week and 24-week interval within 48 weeks in the absence of transfusions
Adult NTD Cohort
Measured: Up to Week 48
Change from baseline in self-reported health-related quality of life (HRQoL) assessed by physical component summary (PCS) and mental component summary (MCS) of 36-item short-form health survey version2 (SF-36v2) at Week 24 and Week 48
Adult TD and NTD Cohorts
Measured: Up to Week 48
Change from baseline in non-transfusion dependent β-thalassemia patient-reported outcome (NTDT-PRO) Tiredness/weakness (T/W) and shortness of breath (SoB) domain scores from Week 13 to Week 24 and from Week 37 to Week 48
Adult NTD Cohort
Measured: Up to Week 48
Change from baseline in FACT-An FS Score at Week 24 and Week 48
Adult NTD Cohort
Measured: Up to Week 48
Change from baseline in Functional Assessment of Cancer Therapy Anemia Anemia Subscale (FACT-An AS) at Week 24 and Week 48
Adult NTD Cohort
Measured: Up to Week 48
Number of participants with at least one hemolytic crisis
Adult TD and NTD Cohorts
Measured: Up to Week 108
Rate of hemolytic crises
Adult TD and NTD Cohorts
Measured: Up to Week 108
Time to first hemolytic crisis
Adult TD and NTD Cohorts
Measured: Up to Week 108
Time to second hemolytic crisis
Adult TD and NTD Cohorts
Measured: Up to Week 108
Change from baseline in hemolysis markers at Week 24 and Week 48
Adult TD and NTD Cohorts:
Measured: Up to Week 48
Change from baseline in the 6-minute walk test (6MWT) distance at Week 24 and Week 48
Adult NTD Cohort
Measured: Up to Week 48
Pharmacokinetics (PK): Serum concentration of Luspatercept
Adult and Adolescent TD and NTD Cohorts
Measured: Up to Week 108
Percent Change from Baseline in Biomarkers for Erythropoiesis at Week 48
Adult and Adolescent TD and NTD Cohorts. The biomarkers for erythropoiesis to be evaluated include sTfR1, erythropoietin (EPO), growth differentiation factor (GDF11), GDF8, GDF15. The change will be measured as a percentage of change from baseline for all the biomarkers.
Measured: Baseline, Week 48
Percent Change from Baseline in Biomarkers and Parameters for Iron Homeostasis at Week 48
Adult TD and NTD Cohorts. The biomarkers and parameters for iron homeostasis to be evaluated include hepcidin, erythroferrone (ERFE), serum ferritin, liver iron concentration (LIC), myocardial iron, iron chelation therapy (ICT). The change will be measured as a percentage of change from baseline for all the biomarkers.
Measured: Up to 5 Years
Percent Change from Baseline in HB Variants including HBH
Adult TD and NTD Cohorts.
Measured: Baseline, Week 48
Change in mean corpuscular volume (MCV) at Week 48
Adult TD and NTD Cohorts
Measured: Baseline, Week 48
Change in mean corpuscular hemoglobin (MCH) at Week 48
Adult TD and NTD Cohorts
Measured: Baseline, Week 48
Change in nucleated red blood cells (nRBC) at Week 48
Adult TD and NTD Cohorts
Measured: Baseline, Week 48
Change in red blood cells (RBC) at Week 48
Adult TD and NTD Cohorts
Measured: Baseline, Week 48
The longest duration with reduction from baseline in the RBC transfusion burden
Adolescent TD Cohort
Measured: Up to Week 48
The number of participants with ≥ 50% reduction from baseline in RBC transfusion burden during an continuous 12 weeks during Weeks 13-48
Adolescent TD Cohort
Measured: Up to Week 48
The number of participants with ≥ 33% reduction from baseline in RBC transfusion burden during an continuous 24 weeks
Adolescent TD Cohort
Measured: Up to Week 48
Number of participants achieving an increase from baseline of ≥1.0g/dL in mean Hb values in absence of transfusions from Week 13 to Week 24
Adolescent NTD Cohort
Measured: Up to Week 24
Cumulative time (in weeks) with an increase from baseline of ≥1.0g/dL in mean Hb values in absence of RBC transfusions within 48 weeks
Adolescent NTD Cohort
Measured: Up to Week 48
Number of participants who achieve an increase in mean Hb of >10g/dL values during any continuous 12-week interval during week 13 to week 48 in the absence of transfusions
Adolescent NTD Cohort
Measured: Up to Week 48
The longest duration with an increase from baseline of ≥1.0g/dL in mean Hb values in absence of transfusions
Adolescent NTD Cohort
Measured: Up to Week 48
Number of participants with antidrug antibody (ADA)
Adolescent TD and NTD Cohorts
Measured: Up to 2 Years
Mean change in biomarkers for hemolysis
Adolescent TD and NTD Cohorts. Biomarkers for hemolysis to be evaluated include total/direct/indirect bilirubin, serum lactate dehydrogenase (sLDH), haptoglobin, reticulocytes and nucleated red blood cells, reticulocyte production index (RPI), and urinary urobilinogen
Measured: Up to Week 48
Mean change in biomarkers and parameters for iron homeostasis
Adolescent TD and NTD Cohorts. The biomarkers and parameters for iron homeostasis to be evaluated include serum ferritin, liver and myocardial iron content (LIC), (MIC), iron chelation therapy (ICT).
Measured: Up to 5 Years
Assessment of Hematologic Parameters
Adolescent TD and NTD Cohorts. The hematologic assessments to be evaluated are red blood cell (RBC) count, hemoglobin, hematocrit, reticulocyte count, nucleated red blood cell count, platelet, leukocyte and neutrophile counts, RBC indices, RBC morphology, and Hb variants.
Measured: Up to Week 48
The change from baseline in the number of health care resource utilization (HCRU)
Adolescent TD and NTD Cohorts
Measured: Up to 5 Years
Mean change from baseline in Pediatric Quality of Life Inventory (PedsQL) domain scores
Adolescent TD and NTD Cohorts
Measured: Up to 3 Years
Mean change from baseline EQ-5D-5L utility index
Adolescent TD and NTD Cohorts
Measured: Up to 3 Years
Mean change from baseline visual analogue scale (VAS) scores
Adolescent TD and NTD Cohorts
Measured: Up to 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2022
- Study start9 Dec 2022
- Primary completion16 Jul 2027 (estimated)
- Study completion14 Aug 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- 189 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05664737
- Sponsor's protocol ID
- CA056-015
- Other IDs
- 2022-502328-35
- Status last verified
- Sep 2026
- First submitted
- 9 Dec 2022
- Last updated
- 10 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Publications
Diamantidis MD, Pitsava S, Zayed O, Argyrakouli I, Karapiperis K, Chatzoulis C, Alexiou E, Manafas A, Tsangalas E, Karakoussis K. Concomitant Presence of Hb Agrinio and - -Med Deletion in a Greek Male Patient with Hemoglobinopathy H: More Severe Phenotype and Literature Review. Hematol Rep. 2023 Aug 8;15(3):483-490. doi: 10.3390/hematolrep15030050.
PubMed 37606495