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    Summary
    EudraCT Number:2021-004928-15
    Sponsor's Protocol Code Number:CA056-015
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-08-08
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGreece - EOF
    A.2EudraCT number2021-004928-15
    A.3Full title of the trial
    A Phase 2, Double-blind, Randomized, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of Luspatercept (BMS-986346/ACE-536) for the Treatment of Anemia in Adults with Alpha (α)-thalassemia
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 2 Study of Luspatercept in Adults with Alpha (α)-thalassemia
    A.3.2Name or abbreviated title of the trial where available
    Phase 2 Study of Luspatercept in Adults with Alpha (α)-thalassemia
    A.4.1Sponsor's protocol code numberCA056-015
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCelgene Corporation
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCelgene Corporation
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBristol-Meyers Squibb International Corporation
    B.5.2Functional name of contact pointGSM-CT
    B.5.3 Address:
    B.5.3.1Street AddressParc de l'Alliance - Avenue de Finlande, 4
    B.5.3.2Town/ cityBraine - l'Allude
    B.5.3.3Post code1420
    B.5.3.4CountryBelgium
    B.5.6E-mailclinical.trials@bms.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Reblozyl
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1331
    D.3 Description of the IMP
    D.3.1Product nameLuspatercept
    D.3.2Product code ACE-536
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLuspatercept
    D.3.9.1CAS number 1373715-00-4
    D.3.9.2Current sponsor codeACE-536
    D.3.9.4EV Substance CodeSUB189400
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Reblozyl
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/14/1331
    D.3 Description of the IMP
    D.3.1Product nameLuspatercept
    D.3.2Product code ACE-536
    D.3.4Pharmaceutical form Lyophilisate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNLuspatercept
    D.3.9.1CAS number 1373715-00-4
    D.3.9.2Current sponsor codeACE-536
    D.3.9.4EV Substance CodeSUB189400
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Alpha (α)-thalassemia
    E.1.1.1Medical condition in easily understood language
    blood condition resulting in the impaired production of hemoglobin
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10054659
    E.1.2Term Thalassemia alpha
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the erythroid response of luspatercept plus BSC vs placebo plus BSC on anemia in participants with α-thalassemia HbH disease
    E.2.2Secondary objectives of the trial
    To compare the RBC transfusion burden effect of luspatercept plus BSC vs placebo plus BSC in participants with α-thalassemia HbH disease
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Participant has documented diagnosis of α-thalassemia HbH disease (electrophoresis⎯ or high-performance liquid chromatography [HPLC]⎯based methods for Hb variant analyses are accepted), with or without transfusion dependence; compounded combination with β-thalassemia is allowed if at least 1 non-mutated β-chain gene is present
    -Transfusion dependence:
    •TD participant ≥ 6 RBC units/24 weeks AND no transfusion-free period for > 56 days during the 24 weeks prior randomization
    •NTD participant: < 6 RBC units during the 24 weeks prior to randomization, RBC transfusion-free during at least 8 weeks prior to randomization
    AND Mean baseline Hb ≤ 10 g/dL
    - Participant must be ≥ 18 years of age at the time of signing the informed consent
    E.4Principal exclusion criteria
    - Diagnosis of α-thalassemia Trait, Hb Bart hydrops, ATRx α-thalassemia, 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 (eg, severe G6PD deficiency, pyruvate kinase deficiency, etc)
    - Bleeding disorders manifested by frequent bleeding episodes (eg, menorrhagia, epistaxis, clotting disorders)
    - Undergone episodes of hemolysis not related to α-thalassemia, eg, after use of hemolysis predisposing drugs (eg, anti-malarial, nonsteroidal anti-inflammatory drug [NSAID]), within the 8 weeks prior to randomization
    - Women who are pregnant, plan to get pregnant during the study, or who are breastfeeding
    - Physical and Laboratory Test Findings
    a) Platelet count > 1,000 × 109 /L b)
    b) Thrombocytopenia with < 70 × 109 /L if not associated with hypersplenism
    c)No concurrent or history of severe hepatic disease or histopathological evidence of liver cirrhosis/fibrosis on liver biopsy: i) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3× the upper limit of normal (ULN) ii) Albumin < 3 g/dL
    d) Heart disease, heart failure as classified by the New York Heart Association (NYHA; see Appendix 6) classification 3 or higher, or significant arrhythmia requiring treatment, or recent myocardial infarction within 6 months of randomization
    e)Lung disease, including pulmonary fibrosis or pulmonary hypertension, which are clinically significant (ie, ≥ Grade 3 per NCI-CTCAE version 5.0 [current active minor version])
    f)Creatinine clearance < 60 mL/min (per Cockroft-Gault formula) or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 (per modification of diet in renal disease [MDRD] study)
    g)Proteinuria ≥ Grade 3 according to NCI-CTCAE version 5.0 (current active minor version) or protein/creatinine ratio > 350 mg/mmol, or albumin/creatinine ratio > 220 mg/mmol
    h)Active hepatitis C virus (HCV) infection, as demonstrated by a positive HCV-RNA test of sufficient sensitivity, or active infectious hepatitis B virus (HBV) as demonstrated by the presence of HBsAg and/or HBV DNA-positive, or known positive human immunodeficiency virus (HIV)
    - Prior/Concomitant Therapy:
    •Treatment with another investigational drug or device ≤ 30 days (or 5 half-lives, whichever is longer) prior to randomization
    •Previous exposure to sotatercept (ACE-011) or luspatercept (BMS-986346/ACE-536)
    •Use of an erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization
    •Iron chelation therapy initiated ≤ 24 weeks prior to randomization
    •Use of hydroxyurea treatment ≤ 24 weeks prior to randomization
    •Prior exposure to gene therapy
    •Undergone HSCT
    E.5 End points
    E.5.1Primary end point(s)
    Transfusion dependent
    Achievement of ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units during any continuous 12 weeks during Weeks 13-48 compared to the 12-week interval immediately prior to the date of first dose

    Non-Transfusion dependent
    Achievement of an increase from baseline of ≥ 1.0 g/dL in mean hemoglobin values over the continuous 12-week interval from Week 13 to Week 24 in the absence of transfusion
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 13 to Week 24
    E.5.2Secondary end point(s)
    Transfusion dependent
    Achievement of ≥ 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 the 24-week interval immediately prior to the date of first dose

    The longest duration with ≥ 50% reduction from baseline in RBC transfusion burden with a reduction of at least 2 units

    Number of RBC transfusion units from Week 1 to Week 48

    Non-Transfusion dependent
    Change from baseline to Week 24 in hemoglobin in the absence of transfusion
    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
    The cumulative time (in weeks) with an increase from baseline of ≥ 1.0 g/dL in hemoglobin values in the absence of transfusion within 48 weeks
    Achievement of ≥ 3 FACT-An FS score increase from baseline to Week 13 to Week 24
    E.5.2.1Timepoint(s) of evaluation of this end point
    Up to 6 years
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    China
    Taiwan
    Thailand
    Greece
    Italy
    Turkey
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    End of trial is defined as the date all participants complete the OLP, if eligible, or discontinue earlier, or the date of receipt of the last data point from the last participant that is required for primary, secondary, and/or exploratory analysis as prespecified in the protocol, whichever is the later date
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days16
    E.8.9.2In all countries concerned by the trial years8
    E.8.9.2In all countries concerned by the trial months0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 172
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 4
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state21
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 26
    F.4.2.2In the whole clinical trial 176
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-09-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-09-28
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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