Myelodysplastic SyndromesPhase 2NCT04419649
A Study of Elritercept to Treat Anemia in Adults With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)
A Phase 2 study testing Elritercept in people with Myelodysplastic Syndromes and Cytopenia, run by Takeda at 53 sites in 8 countries.
Trial summary
The main aim of this study is to learn how safe elritercept is and how well adults with anemia associated with lower-risk MDS tolerate treatment with different doses of elritercept. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes, Cytopenia
- What is being tested?
- Elritercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 210 participants
- Where
- 53 sitesin 8 countries
- Study dates
- 19 Aug 2020to 30 Oct 2031
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local study participant privacy regulations.
- Male or female ≥ 18 years of age, at the time of signing informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
- Females of childbearing potential and sexually active males must agree to use highly effective methods of contraception.
- In the opinion of the Investigator, the participant is able and willing to comply with the requirements of the protocol (e.g., all study procedures, return for follow-up visits).
- Part 1 Inclusion Criteria
Show all 175Show fewer
- Participants are eligible to be included in Part 1 of the study only if all the following criteria apply:
- Diagnosis of MDS according to WHO classification that meets International Prognostic Scoring System-Revised (IPSS-R) classification of very low, low, or intermediate risk disease.
- Less than (<)5 percent (%) blasts in bone marrow during the Pretreatment Period.
- Peripheral blood white blood cell (WBC) count <13,000/microliter (μL) during the Pretreatment Period.
- Anemia defined as:
- In non-transfused participants, having received no RBC transfusions within 8 weeks, Hgb concentration ≤ 10.0 g/dL during the Pretreatment Period. OR
- In LTB participants, having received 1 to 3 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period. OR
- In HTB participants, having received ≥ 4 units of RBCs for Hgb ≤ 9.0 g/dL within 8 weeks of the Pretreatment Period.
- Part 1 Extension - Abbreviated Inclusion Criteria
- Participants from Part 1 are eligible to be included in Part 1 Extension of the study only if all the following criteria apply:
- Previously completed 4 cycles of elritercept in Part 1 with no dose-limiting toxicities (DLTs).
- Participant has the potential to benefit from administration of elritercept, in the opinion of the Investigator.
- < 5% blasts in bone marrow.
- Peripheral WBC count < 13,000/μL during the 28 days prior to cycle 5 day 1 (C5D1).
- Part 2 Inclusion Criteria
- Participants are eligible to be included in Part 2 of the study only if all the following criteria apply:
- Cohort A:
- Diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
- ring sideroblast (RS)-positive as defined by WHO 2016 criteria.
- Requiring at least 2 units of RBC transfusions in the preceding 8 weeks before cycle 1 day 1 (C1D1).
- Cohort B:
- Diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
- Non-RS as defined by WHO 2016 criteria.
- Requiring at least 2 units of RBC transfusions in the 8 weeks before C1D1.
- Cohort C:
- Diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
- Has anemia, defined by Hgb ≤ 10 g/dL during the Pretreatment Period, and received no RBC transfusion in the 8 weeks before C1D1.
- Cohort D:
- Diagnosis of CMML according to WHO 2016 classification.
- Has anemia, defined by Hgb ≤ 10 g/dL during the Pretreatment Period, and received no RBC transfusion in the 8 weeks before C1D1. OR
- Received at least 2 units of RBC transfusions for anemia in the 8 weeks before C1D1.
- Cohort E:
- Diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
- Requiring ≥ 2 units of RBC transfusions in the preceding 8 weeks before C1D1.
- Receipt of ≥ 20 units of RBC in transfusion over the participant's lifetime.
- Serum ferritin > 1000 nanograms per milliliter (ng/mL) on ≥ 2 assessments in the preceding 8 weeks before C1D1.
- Treated with stable dose of iron chelation therapy for ≥ 8 weeks prior to C1D1.
- Cohort F:
- Diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
- Requiring ≥ 2 units of RBC transfusions in the preceding 8 weeks before C1D1.
- Receipt of ≥ 20 units of RBC in transfusion over the participant's lifetime.
- Serum ferritin > 1000 ng/mL on ≥ 2 assessments in the preceding 8 weeks before C1D1.
- Not treated with iron chelation therapy in the preceding 8 weeks before C1D1 and not eligible to initiate iron chelation therapy in the opinion of the Investigator and in accordance with local treatment guidelines for initiation of iron chelation therapy.
- Cohort G:
- Diagnosis of MDS according to WHO 2016 classification that meets IPSS-R classification of very low, low, or intermediate risk disease.
- RS-positive as defined by WHO 2016 criteria OR non-RS as defined by WHO 2016 criteria.
- Relapsed, refractory, or intolerant to luspatercept treatment
- Relapsed is defined as documentation of response to luspatercept therapy followed by subsequent development of a need for transfusion(s), whether the transfusion need develops during luspatercept treatment or after luspatercept has been discontinued.
- Refractory is defined as documentation of no response with luspatercept ≥ 1 mg/kg administered for ≥ 12 weeks duration.
- Intolerant is defined as documentation of discontinuation of luspatercept therapy due to intolerance including, discontinuation because of any adverse event (serious or nonserious) at any time after treatment initiation.
- Has anemia, defined as either of the following:
- Has received at least 1 unit of RBC transfusions for anemia in the 8 weeks before C1D1; OR
- Hgb ≤ 10 g/dL, and received no RBC transfusion in the 8 weeks before C1D1
- Erythropoietin (EPO) < 500 international units per liter (U/L) at Baseline.
- Last dose of luspatercept is ≥ 3 weeks from C1D1.
- < 5% blasts in bone marrow assessed by bone marrow aspirate during the Pretreatment Period.
- Part 1 Exclusion Criteria
- Participants are excluded from Part 1 of the study if any of the following criteria apply.
- Medical History
- Diagnosis of MDS with deletion of chromosome 5q (Del5q).
- Active infection requiring parenteral antibiotic therapy within 28 days prior to C1D1 or oral antibiotics within 14 days of C1D1. Prophylactic antibiotics and/or antifungals for neutropenia are allowed.
- Presence of uncontrolled heart disease or New York Heart Association (NYHA) Class III or IV heart failure.
- History of drug or alcohol abuse (as defined by the Investigator) within the past 2 years.
- History of stroke, deep venous thrombosis (DVT), or arterial embolism within 6 months prior to C1D1.
- Major surgery within 28 days prior to C1D1. Participants must be completely recovered from any previous surgery prior to C1D1.
- Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B virus (HBV), or active infectious hepatitis C virus (HCV). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
- Any malignancy other than MDS that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or surgery, within 1 year prior to C1D1. Diagnosis of secondary MDS (i.e., MDS known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
- History of solid organ or hematological transplantation.
- Presence of uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 150 mmHg or diastolic BP ≥ 100 mmHg despite adequate treatment.
- Body mass index (BMI) ≥ 40 kilograms per meter square (kg/m^2) during the Pretreatment Period.
- History of severe allergic or anaphylactic reaction(s) or hypersensitivity to recombinant proteins or excipients in the investigational medicinal product (IMP).
- Treatment History
- Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept.
- Treatment with ESA within 56 days prior to C1D1.
- Prior or concurrent chronic treatment with granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF).
- Iron chelation therapy if initiated within 8 weeks prior to C1D1.
- Vitamin B12 therapy initiated within 8 weeks prior to C1D1. Participants on stable replacement doses for ≥ 8 weeks and without concurrent vitamin B12 or folate deficiency are allowed.
- Treatment with another investigational drug or device or approved therapy for investigational use ≤ 28 days prior to C1D1, or, if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer.
- Laboratory Exclusions (during Pretreatment Period)
- Platelet count > 450 ✕ 10^9/L or < 30 ✕ 10^9/L.
- Transferrin saturation < 15%.
- Ferritin < 50 nanograms per milliliter (ng/mL).
- Folate < 4.5 nanomoles per liter (nmol/L) (< 2.0 ng/mL).
- Vitamin B12 < 148 picomoles per liter (pmol/L) (< 200 picograms per milliliter [pg/mL]).
- Estimated glomerular filtration rate (GFR) < 30 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2), as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
- Positive for HIV.
- Miscellaneous
- Pregnant or lactating females.
- Any other condition not specifically noted above which, in the opinion of the Investigator, would preclude the participant from participating in the study.
- Participants who are investigational site staff members directly involved in the conduct of the trial and their immediate family members, site staff members otherwise supervised by the Investigator, or participants who are Sponsor or contract research organization (CRO) employees directly involved in the conduct of the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- Part 1 Extension - Exclusion Criteria
- Participants from Part 1 are excluded from Part 1 Extension of the study if any of the following criteria apply.
- Medical History
- Discontinuation of IMP in Part 1 for any reason.
- Has not completed a study visit in the past 12 months.
- Active infection requiring parenteral antibiotic therapy within 28 days prior to C5D1 or oral antibiotics within 14 days of C5D1. Prophylactic antibiotics and/or antifungals for neutropenia are allowed.
- Presence of uncontrolled heart disease or NYHA Class III or IV heart failure.
- History of drug or alcohol abuse (as defined by the Investigator) within the past 2 years.
- History of stroke, DVT, or arterial embolism within 6 months prior to C5D1.
- Major surgery within 28 days prior to C5D1. Participants must be completely recovered from any previous surgery prior to C5D1.
- Known positive for HIV, active infectious HBV, or active infectious HCV. Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
- Any malignancy other than MDS that has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy, or surgery, within 1 year prior to C5D1.
- History of solid organ or hematological transplantation.
- Presence of uncontrolled hypertension, defined as systolic BP ≥ 150 mmHg or diastolic BP ≥ 100 mmHg despite adequate treatment.
- BMI ≥ 40 kg/m^2 during the 28 days prior to C5D1.
- Treatment History
- Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept.
- Treatment with ESA within 56 days prior to C5D1.
- Prior or concurrent chronic treatment with G-CSF or GM-CSF.
- Iron chelation therapy if initiated within 8 weeks prior to C5D1.
- Vitamin B12 with treatment initiated within 8 weeks prior to C5D1. Participants on stable replacement doses for ≥ 8 weeks and without concurrent vitamin B12 or folate deficiency are allowed.
- Treatment with another investigational drug or device or approved therapy for investigational use ≤ 28 days prior to C5D1, or, if the half-life of the previous product is known, within 5 times the half-life prior to C5D1, whichever is longer. Previous treatment with elritercept is acceptable.
- Laboratory Exclusions (during Abbreviated Pretreatment Period)
- Platelet count > 450 × 10^9/L or < 30 × 10^9/L.
- Transferrin saturation < 15%.
- Ferritin < 50 ng/mL.
- Folate < 4.5 nmol/L (< 2.0 ng/mL).
- Vitamin B12 < 148 pmol/L (< 200 pg/mL).
- Estimated GFR < 30 mL/min/1.73 m^2, as determined by the CKD-EPI equation.
- Miscellaneous
- Pregnant or lactating females.
- Any other condition not specifically noted above which, in the opinion of the Investigator, would preclude the participant from participating in the study.
- Participants who are investigational site staff members directly involved in the conduct of the trial and their immediate family members, site staff members otherwise supervised by the Investigator, or participants who are Sponsor or CRO employees directly involved in the conduct of the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- Part 2 Exclusion Criteria
- Participants are excluded from Part 2 of the study if any of the following criteria apply.
- Medical History
- Diagnosis of MDS with Del5q.
- Diagnosis of secondary MDS (i.e., MDS known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
- Active infection requiring parenteral antibiotic therapy within 28 days prior to C1D1 or oral antibiotics within 14 days of C1D1. Prophylactic antibiotics and/or antifungals for neutropenia are allowed.
- Presence of the following cardiac conditions:
- Presence of uncontrolled heart disease or NYHA Class III or IV heart failure.
- QTcF (QT interval corrected by Fridericia's formula) > 500 msec on the screening or C1D1 electrocardiogram (ECG; mean of 3 measurements).
- Uncontrolled clinically significant arrhythmia (participants with rate-controlled atrial fibrillation are not excluded).
- Acute myocardial infarction or unstable angina pectoris ≤ 6 months prior to C1D1.
- Presence of uncontrolled hypertension, defined as systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite adequate treatment.
- History of stroke, DVT, or arterial embolism within 6 months prior to C1D1.
- History of drug or alcohol abuse (as defined by the Investigator) within the past 2 years.
- Major surgery within 28 days prior to C1D1. Participants must be completely recovered from any previous surgery prior to C1D1.
- Any malignancy other than MDS or CMML that has not been in remission and/or has required major surgery or systemic therapy including radiation, chemotherapy, targeted therapy, or hormonal therapy within 1 year prior to C1D1.
- History of solid organ or hematological transplantation.
- Diagnosis of hemolytic anemia, active bleeding, hemoglobinopathies, or congenital disorders as a cause of the participant's anemia.
- NCI-CTCAE Grade ≥ 2 bleeding events within the 3 months prior to C1D1.
- Receipt of an RBC or platelet transfusion for any reason(s) or combination of reasons other than underlying MDS within the 16 weeks prior to C1D1. If a participant requires a transfusion for an unanticipated reason during the Pretreatment Period, a prolonged screening period may be considered after discussion with the Medical Monitor.
- Known positive for HIV, active infectious HBV with positive viral load (HBV DNA), or active infectious HCV with positive viral load (HCV RNA). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
- BMI ≥ 40 kg/m^2.
- History of severe allergic or anaphylactic reaction(s) or hypersensitivity to recombinant proteins or excipients in the IMP.
- Diagnosis of cirrhosis, non-alcoholic steatohepatitis, alcoholic liver disease, hepatitis, or other liver disease (acute or chronic) meeting Child-Pugh C criteria for hepatic impairment. Participants with elevated liver enzymes are allowed if the liver enzyme elevation is suspected to be due to iron-overload or iron chelation, and other hepatic causes have been ruled out, in the opinion of the Investigator.
- Treatment History
- Prior treatment with azacitidine, decitabine, lenalidomide, or sotatercept.
- Prior treatment with luspatercept (Cohorts A, B, C, D, E, and F only).
- Treatment with ESA within 8 weeks prior to C1D1.
- Iron chelation therapy if initiated within 8 weeks prior to C1D1. Participants on stable doses of iron chelation therapy for ≥ 8 weeks are allowed.
- Vitamin B12 and/or folate therapy initiated within 8 weeks prior to C1D1. Participants on stable replacement doses for ≥ 8 weeks and without concurrent vitamin B12 or folate deficiency are allowed.
- Any need to receive a prohibited medication.
- Treatment with another investigational drug or device or approved therapy for investigational use within 8 weeks prior to C1D1, or, if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer.
- Laboratory Exclusions (during Pretreatment Period)
- Platelet count > 800 × 10^9/L or < 25 × 10^9/L.
- Ferritin < 50 ng/mL.
- Folate < 4.5 nmol/L (< 2.0 ng/mL).
- Vitamin B12 < 148 pmol/L (< 200 pg/mL).
- Estimated GFR < 30 mL/min/1.73 m^2 as determined by the CKD-EPI equation.
- Miscellaneous
- Pregnant or lactating females.
- Any other condition not specifically noted above which, in the opinion of the Investigator, would preclude the participant from participating in the study.
- Participants who are investigational site staff members directly involved in the conduct of the trial and their immediate family members, site staff members otherwise supervised by the Investigator, or participants who are Sponsor or CRO employees directly involved in the conduct of the study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- For Cohort G ONLY:
- Any luspatercept related AE Grade ≥ 3 that has not resolved to baseline or Grade ≤ 1.
- History of allergy/anaphylaxis/hypersensitivity to luspatercept.
- Prior treatment with imetelstat.
Who cannot join
None listed.
Trial locations and contacts
53 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
53 sites in 8 countries
Australia12 sites, 10 recruiting
- Recruiting
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Site Contact, devendra.hiwase@sa.gov.au
Devendra Hiwase
- Recruiting
Border Medical Oncology Research
Albury, New South Wales, 2640
Site Contact, APuliyayil@bordermedonc.com.au
Anish Puliyayil
- Recruiting
Flinders Medical Centre
Bedford Park, South Australia, 5042
Site Contact, david.ross@sa.gov.au
David Ross
- Recruiting
Boxhill Hospital
Box Hill, Victoria, 3128
Site Contact, t.teh@alfred.org.au
Tse-Chieh Teh
- Completed
Townsville University Hospital
Douglas, Queensland, 4814
- Recruiting
University Hospital Geelong
Geelong, Victoria, 3220
Site Contact, HANNAH.ROSE@barwonhealth.org.au
Hannah Rose
- Recruiting
Austin Health
Heidelberg, Victoria, 3084
Site Contact, chun.fong@austin.org.au
Chun Yew Fong
- Recruiting
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Site Contact, lynette.chee@mh.org.au
Lynette Chee
- Recruiting
St Vincent's Hospital Melbourne
Melbourne, Victoria, 3065
Site Contact, shuhying.tan@svha.org.au
Shuhying Tan
- Recruiting
Tweed Hospital
Tweed Heads, New South Wales, 2485
Site Contact, Alejandro.ArbelaezAcevedo@health.nsw.gov.au
Alejandro Arbelaez
- Completed
Ballarat Oncology & Haematology Service
Wendouree, Victoria, 3355
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
Site Contact, john.kwan@health.nsw.gov.au
John Kwan
United States11 sites, 9 recruiting
- Recruiting
The Center for Cancer and Blood Disorders (CCBD) - Bethesda
Bethesda, Maryland, 20817
Site Contact, Victor.Priego@aoncology.com
Victor Priego
- Recruiting
City of Hope National Medical Center
Duarte, California, 91010
Site Contact, aartz@coh.org
Andrew Artz
- Recruiting
Hackensack Medical Center
Hackensack, New Jersey, 07601
Site Contact, jamie.koprivnikar@hmhn.org
Jamie Koprivnikar
- Recruiting
Genesis Cancer and Blood Institute
Hot Springs, Arkansas, 71913
Site Contact, Lingyi.Chen@aoncology.com
Lingyi Chen
- Recruiting
Univ of Texas MD Anderson Cancer Center, Division of Cancer Medicine
Houston, Texas, 77030
Site Contact, ggarciam@mdanderson.org
Guillermo Garcia-Manero
- Completed
Karmanos Cancer Institute at Mclaren Greater Lansing
Lansing, Michigan, 48910
- Recruiting
Baptist Clinical Research Institute
Memphis, Tennessee, 38120
Site Contact, muhammad.raza@bmg.md; Muhammad.Raza@BMHCC.org
Muhammad Raza
- Recruiting
University of Miami School of Medicine Sylvester Comprehensive Cancer Center (SCCC)
Miami, Florida, 33136
Site Contact, msekeres@med.miami.edu
Mikkael Sekeres
- Completed
University of Pittsburgh Medical Health Center
Pittsburgh, Pennsylvania, 15213
- Recruiting
New York Cancer and Blood
Shirley, New York, 11967
Site Contact, zunigaresearch@nycancer.com
Richard Zuniga
- Recruiting
H. Lee Moffitt Cancer Center and Research Center
Tampa, Florida, 33612
Site Contact, Rami.Komrokji@moffitt.org
Rami Komrokji
Germany11 sites, 8 recruiting
- Recruiting
Klinikum Bayreuth GmbH
Bayreuth
Site Contact, alexander.kiani@klinikum-bayreuth.de
Alexander Kiani
- Not yet recruiting
Charite-Campus Benjamin Franklin
Berlin
Site Contact, kathrin.rieger@charite.de
Kathrin Rieger
- Not yet recruiting
Praxis am Volkspark Berlin
Berlin
Site Contact, jp.habbel@praxis-am-volkspark-berlin.de
Jan-Piet Habbel
- Not yet recruiting
University Hospital Bonn
Bonn
Site Contact, karin.mayer@ukbonn.de
Karin Mayer
- Recruiting
Marien Hospital Dusseldorf GMBH
Düsseldorf
Site Contact, aristoteles.giagounidis@vkkd-kliniken.de
Aristoteles Giagounidis
- Completed
Universitaetsklinikum Duesseldorf AoeR
Düsseldorf
- Recruiting
Klinikum Esslingen GmbH
Esslingen am Neckar
Site Contact, s.wessendorf@klinikum-esslingen.de
Swen Wessendorf
- Not yet recruiting
University Hospital Halle (Saale)
Halle
Site Contact, haifa.al-ali@uk-halle.de
Haifa Al-Ali
- Completed
Universitaetsklinikum Leipzig AoeR
Leipzig
- Recruiting
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Mainz
Site Contact, daniel.sasca@unimedizin-mainz.de
Daniel Sasca
- Completed
Universitaetsmedizin Rostock
Rostock
France7 sites, 5 recruiting
- Completed
CHU Angers - Hopital Hotel Dieu
Angers
- Completed
Centre Hospitalier de la Region dAnnecy
Épagny
- Recruiting
CHU de Nantes - Hotel Dieu
Nantes
Site Contact, alice.garnier@chu-nantes.fr
Alice Garnier
- Recruiting
CHU Nice - Hopital de l'Archet 1
Nice
Site Contact, cluzeau.t@chu-nice.fr
Thomas Cluzeau
- Recruiting
Hopital Saint-Louis
Paris
Site Contact, lionel.ades@aphp.fr
Lionel Ades
- Recruiting
CH Rene-Dubos
Pontoise
Site Contact, riad.benramdane@ght-novo.fr
Riad Benramdane
- Recruiting
CHU de Bordeaux - Hopital Haut-Leveque
Talence
Site Contact, sophie.dimicoli-salazar@chu-bordeaux.fr
Sophie Dimicoli Salazar
Spain6 sites, 5 recruiting
- Recruiting
Hospital Universitario Central de Asturias
Barcelona
Site Contact, bernalmaria@uniovi.es
Teresa Bernal del Castillo
- Recruiting
Hospital Universitario Vall d'Hebron
Barcelona
Site Contact, dvalcarcelct@vhio.net
David Valcarcel Ferreiras
- Recruiting
ICO l'Hospitalet - Hospital Duran i Reynals
Barcelona
Site Contact, marnan@iconcologia.net
Montserrat Arnan Sangerman
- Recruiting
Hospital Universitario de Salamanca
Salamanca
Site Contact, mdiezcampelo@usal.es
Maria Diez Campelo
- Completed
Hospital Universitario Virgen del Rocio
Seville
- Recruiting
Hospital Universitari i Politecnic La Fe
Valencia
Site Contact, mora_elv@gva.es
Elvira Mora Castera
Czechia3 sites, 1 recruiting
- Completed
Fakultni nemocnice Brno
Brno
- Recruiting
Fakultni nemocnice Kralovske Vinohrady
Prague
Site Contact, cerna@fnkv.cz
Olga Cerna
- Completed
Vseobecna Fakultni Nemocnice Praha
Prague
Israel2 sites, 1 recruiting
- Recruiting
Sheba Medical Center - Sheba Fund for Health Services and Research
Ramat Gan, 52621
Site Contact, Drorit.Merkel@sheba.health.gov.il
Drorit Merkel
- Completed
Sourasky Medical Center - Infrastructure and Health Services Fund of the Tel Aviv Medical Center
Tel Aviv, 6423906
About this study
Official title: A Phase 2, Open-Label, Ascending Dose Study of KER-050 for the Treatment of Anemia in Patients With Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS)
The main aim of this study is to learn how safe elritercept is and how well adults with anemia associated with lower-risk MDS tolerate treatment with different doses of elritercept. Other aims are to learn how safe elritercept is by looking at how many participants have MDS that worsens during the study and learn about the effects of elritercept on anemia linked to MDS. The study will also look to learn how elritercept affects the production of healthy RBCs.
Read the detailed description
Elritercept (KER-050) is a recombinant fusion protein being studied to increase red blood cell production by inhibiting the signaling of a subset of the transforming growth factor beta (TGF-ß) family of proteins.
- Conditions
- Myelodysplastic Syndromes, Cytopenia
- Being tested
- Elritercept
- Keywords
- Transfusion, Drug Therapy, Elritercept, TAK-226, KER-050
- Medical subject headings
- Myelodysplastic Syndromes, Cytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElriterceptDrug
Also called KER-050, TAK-226
Elritercept SC injection.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Elritercept Cohort 1 | Experimental | Participants will be administered elritercept at 0.75 milligrams per kilogram (mg/kg), subcutaneous (SC) injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days). Receives: Drug: Elritercept |
| Part 1: Elritercept Cohort 2 | Experimental | Participants will be administered elritercept at 1.5 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days). Receives: Drug: Elritercept |
| Part 1: Elritercept Cohort 3 | Experimental | Participants will be administered elritercept at 2.5 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days). Receives: Drug: Elritercept |
| Part 1: Elritercept Cohort 4 | Experimental | Participants will be administered elritercept at 3.75 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles (each cycle = 28 days). Receives: Drug: Elritercept |
| Part 1: Elritercept Cohort 5 | Experimental | Participants will be administered elritercept at 5.0 mg/kg, SC injection, every 4 weeks on Day 1 of each cycle for up to 4 cycles (each cycle = 28 days). Following the above dose regimen, participants will continue to receive elritercept, administered SC, on Day 1, every 4 weeks up to 24 cycles(each cycle = 28 days). Receives: Drug: Elritercept |
| Part 2: Elritercept Dose Confirmation Cohort A | Experimental | Participants with ring sideroblasts (RS)-positive Myelodysplastic syndrome (MDS) who are requiring red blood cell (RBC) transfusions will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Part 2: Elritercept Dose Confirmation Cohort B | Experimental | Participants with non-RS MDS who are requiring RBC transfusions will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Part 2: Elritercept Dose Confirmation Cohort C | Experimental | Participants who are non-transfused with either RS-positive MDS or non-RS MDS will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Experimental: Part 2: Elritercept Dose Confirmation Cohort D | Experimental | Participants with chronic myelomonocytic leukemia (CMML) and anemia will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Part 2: Elritercept Dose Confirmation Cohort E | Experimental | Participants with MDS (either RS-positive or non-RS) who are requiring RBC transfusions, have iron-overload, and are receiving iron chelation therapy will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Part 2: Elritercept Dose Confirmation Cohort F | Experimental | Participants with MDS (either RS-positive or non-RS) who are requiring RBC transfusions, have iron-overload, and are not receiving iron chelation therapy will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Part 2: Elritercept Dose Confirmation Cohort G | Experimental | Participants with MDS (either RS-positive or non-RS) who have relapsed after treatment with luspatercept, become refractory to luspatercept treatment, or are intolerant to luspatercept treatment will be administered Elritercept at 3.75 mg/kg, SC injection, on Day 1, every 4 weeks for up to 24 cycles (each cycle = 28 days). The dose can be modified based on participant's response. Receives: Drug: Elritercept |
| Long-term Extension Cohort | Experimental | Participants from Part 1 and 2 cohorts who may have potential benefit from continued elritercept treatment, in the opinion of the Investigator, may elect to continue in the LTE at the same dose they were being administered in Part 1 and 2, SC injection, on day 1, every 4 weeks until end of treatment (EOT) (approximately 122 months). Receives: Drug: Elritercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence, in a clinical study participant administered a medicinal product, that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not it is related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.
Measured: From treatment initiation to end of study (up to 11.2 years)
Secondary outcomes (12)
Number of Participants with Progression to Higher Risk MDS or Acute Myeloid Leukemia (AML)
The progression to higher risk MDS or AML will be assessed as per the World Health Organization (WHO) 2016 criteria.
Measured: From study day 1 through end of study (up to 11.2 years)
Percentage of Participants with Low Transfusion Burden (LTB) and High Transfusion Burden (HTB) who Achieve RBC Transfusion Independence (TI)
Participants with LTB and HTB achieving RBC TI greater than or equal to (≥) 8 weeks, overall RBC TI and based on RS status will be assessed.
Measured: From study day 1 through end of study (up to 11.2 years)
Percentage of Participants who Achieve Hematologic Improvement Erythroid (HI-E) Response Based on Modified 2006 International Working Group (IWG)
The response is defined as a mean hemoglobin (Hgb) increase of ≥1.5 grams per deciliter (g/dL) from Baseline during any 8-week period during the treatment period for LTB participants and participants with non-transfused anemia, and is defined as a reduction by ≥ 4 units of RBCs transfused during any 8-week period on study compared with the 8-week period prior to study cycle 1 day 1 (C1D1) (cycle length = 28 days) for HTB participants. Participants achieving overall HI-E response and based on RS status will be assessed.
Measured: From study day 1 to end of study (up to 11.2 years)
Percentage of Participants who Achieve Overall Erythroid Response
The response is defined as a mean hemoglobin (Hgb) increase of ≥1.5 grams per deciliter (g/dL) from Baseline during any 8-week period during the treatment period for LTB participants and participants with non-transfused anemia, and is defined as a reduction by ≥ 4 units of RBCs transfused during any 8-week period on study compared with the 8-week period prior to study cycle 1 day 1 (C1D1) (cycle length = 28 days) for HTB participants. TI is defined as RBC transfusion independence for ≥ 8 weeks. Overall erythroid response is defined as HI-E or TI over any 8-week period. Participants achieving overall erythroid response and based on RS status will be assessed.
Measured: Up to approximately 11.2 years
Percentage of Participants who Achieve Erythropoietic Improvement
The improvement is defined as a mean Hgb increase of ≥1.5 g/dL from Baseline for ≥14 days (in the absence of RBC transfusions) for LTB participants and participants with non-transfused anemia and is defined as a reduction of ≥50% or ≥4 RBC units transfused compared with pretreatment over an 8-week period for HTB participants. Participants achieving overall improvement and based on RS status will be assessed.
Measured: Up to approximately 11.2 years
Mean Change from Baseline in Hgb
At each visit, the mean of the change from baseline in Hgb will be calculated across participants.
Measured: Baseline, multiple timepoints post treatment up to 11.2 years
Time to HI-E Response
The response is defined as a mean hemoglobin (Hgb) increase of ≥1.5 grams per deciliter (g/dL) from Baseline during any 8-week period during the treatment period for LTB participants and participants with non-transfused anemia, and is defined as a reduction by ≥ 4 units of RBCs transfused during any 8-week period on study compared with the 8-week period prior to study cycle 1 day 1 (C1D1) (cycle length = 28 days) for HTB participants.
Measured: Up to approximately 11.2 years
Duration of HI-E Response
The response is defined as a mean hemoglobin (Hgb) increase of ≥1.5 grams per deciliter (g/dL) from Baseline during any 8-week period during the treatment period for LTB participants and participants with non-transfused anemia, and is defined as a reduction by ≥ 4 units of RBCs transfused during any 8-week period on study compared with the 8-week period prior to study cycle 1 day 1 (C1D1) (cycle length = 28 days) for HTB participants.
Measured: Up to approximately 11.2 years
Time to TI Response
TI is defined as RBC transfusion independence for ≥ 8 weeks.
Measured: Up to approximately 11.2 years
Duration of TI response
TI is defined as RBC transfusion independence for ≥ 8 weeks.
Measured: Up to approximately 11.2 years
Percentage of LTB and HTB Participants who Achieve TI
Measured: Weeks 12, 16, 24 and 48
Number of Participants with Change from Baseline in Red Cell Parameters
The red cell parameters including reticulocyte count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and reticulocyte cell Hgb will be assessed.
Measured: Up to approximately 11.2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2020
- Study start19 Aug 2020
- Primary completion30 Oct 2029 (estimated)
- Study completion30 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by TakedaThe 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- Ascending dose study
- Masking
- None (open label)
- Enrolment
- 210 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04419649
- Sponsor's protocol ID
- KER050-MD-201
- Other IDs
- 2023-507469-24-00, 2023
- Status last verified
- Oct 2026
- First submitted
- 3 Jun 2020
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.