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An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Adults Who Require Regular Red Blood Cell Transfusions Due to Beta (β) Thalassemia (BELIEVE)

Primary Purpose

Erythrocyte Transfusion, Beta-Thalassemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Luspatercept
Placebo
Sponsored by
Celgene
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Erythrocyte Transfusion focused on measuring ACE-536, Safety, Efficacy, Placebo, Red Blood Cell Transfusions, Beta -Thalassemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Male or female, ≥18 years of age at the time of signing the informed consent document (ICF).
  2. Subject must understand and voluntarily sign an Inform Consent Form prior to any study-related assessments/procedures being conducted.
  3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
  4. Documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia. (β-thalassemia with mutation and/or multiplication of alpha globin is allowed).
  5. Regularly transfused, defined as: 6-20 Red Blood Cell (RBC) units* in the 24 weeks prior to randomization and no transfusion-free period for ≥ 35 days during that period.

    * Sites who prescribe transfusions and have the transfusion records only in volumes should use for conversion of volume to units the below criteria, in order to obtain number of units within the last 24 weeks to assess the eligibility: 1 unit in this protocol refers to a quantity of packed RBCs approximately 200-350 mL. (i) sites who use transfusion bags within this range, or ≥ 350 mL, the conversion in units should be done by dividing the volume transfused to the patient by 350 mL, (ii) sites who use transfusion bags < 200 mL, the conversion in units should be done by dividing the volume transfused to the patient by 200 mL.

  6. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
  7. 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). FCBP participating in the study must:

    1. Have two 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.
    2. 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 with, effective*** contraception without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks (approximately five times the mean terminal half-life of luspatercept based on multiple-dose Pharmacokinetic PK) data) after discontinuation of study therapy.

      • True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.] *** Agreement to use highly effective methods of contraception that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study.

    Such methods include: Combined (estrogen and progesterone/progestin containing) hormonal contraception: Oral; Intravaginal; Transdermal; Progestogen/progestin only hormonal contraception associated with inhibition of ovulation: Oral; Injectable hormonal contraception; Implantable hormonal contraception; Placement of an intrauterine device (IUD); Placement of an intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomized partner; Sexual Abstinence.

  8. Male subjects must:

    • Practice true abstinence 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 five times the mean terminal half-life of luspatercept based on multiple-dose PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

  1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  3. Any condition that confounds the ability to interpret data from the study.
  4. A diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H);
  5. Evidence of active hepatitis C (HCV) infection as demonstrated by a positive HCV-RNA test of sufficient sensitivity, or active infectious hepatitis B as demonstrated by the presence of HBsAg and/or HBVDNA-positive,, or known positive human immunodeficiency virus (HIV).

    Note: Subjects receiving antiviral therapies should have 2 negative HCVRNA tests 3 months apart.(ie, one test at the end of the antiviral therapy and a second test 3 months following the first test).

  6. Deep Vein Thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
  7. Use of chronic anticoagulant therapy is excluded, unless the treatment stopped at least 28 days prior to randomization. Anticoagulant therapies used for prophylaxis for surgery or high risk procedures as well as low Molecular Weight (LMW) heparin for superficial venous thrombosis and chronic aspirin are allowed.
  8. Platelet count > 1000 x 109/L
  9. Poorly controlled diabetes mellitus within 24 weeks prior to randomization as defined by short term (eg, hyperosmolar or ketoacidotic crisis) and/or history of diabetic cardiovascular complications (eg, stroke or myocardial infarction).
  10. Treatment with another investigational drug or device ≤ 28 days prior to randomization.
  11. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
  12. Use of an erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization.
  13. Iron chelation therapy, if initiated ≤ 24 weeks prior to randomization (allowed if initiated > 24 weeks before or during treatment).
  14. Hydroxyurea treatment ≤ 24 weeks prior to randomization.
  15. Pregnant or lactating females.
  16. Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (current active minor version).
  17. Major organ damage, including:

    1. Liver disease with alanine aminotransferase (ALT) > 3 x the upper limit of normal (ULN) or history of evidence of cirrhosis;
    2. 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 within 6 months of randomization.
    3. Lung disease, including pulmonary fibrosis or pulmonary hypertension which are clinically significant ie, ≥ Grade 3 NCI CTCAE version 4.0 (current active minor version).
    4. Creatinine clearance < 60 mL/min (per Cockroft-Gault formula).
  18. Proteinuria ≥ Grade 3 according to NCI CTCAE version 4.0 (current active minor version).
  19. Chronic systemic glucocorticoids ≤ 12 weeks prior to randomization (physiologic replacement therapy for adrenal insufficiency is allowed). Single day glucocorticoid treatment (eg, for prevention or treatment of transfusion reactions, is allowed).
  20. Major surgery ≤ 12 weeks prior to randomization (subjects must have completely recovered from any previous surgery prior to randomization).
  21. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator Brochure).
  22. Cytotoxic agents, immunosuppressants ≤ 28 days prior to randomization (ie, antithymocite globulin (ATG) or cyclosporine)
  23. History of malignancy with the exception of:

    1. Curatively resected nonmelanoma skin cancer.
    2. Curatively treated cervical carcinoma in situ.
    3. Other solid tumor with no known active disease in the opinion of the investigator.

Sites / Locations

  • Children's Hospital of Los Angeles
  • Children's Hospital and Research Center at Oakland
  • Ann and Robert H Lurie Childrens Hospital of Chicago
  • Boston Children's Hospital
  • Weill Cornell Medical College
  • Hospital of the University of Pennsylvania
  • Prince of Wales Hospital
  • Mater Hospital Brisbane
  • Royal Adelaide Hospital Institute of Medical and Veterinary Science
  • Monash Medical Centre
  • Sir Charles Gairdner Hospital
  • Royal Prince Alfred Hospital
  • University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
  • Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
  • Multiprofile Hospital for Active Treatment Sveta Marina EAD
  • University Health Network
  • Hopital Henri Mondor
  • GH de Institut Catholique St. VincentHématologie
  • Hopitaux de La Timone
  • Hospital of Necker
  • Laiko General Hospital of Athens
  • Local Institution - 405
  • General Children's Hospital "Agia Sophia"
  • General Hospital Georgios Gennimatas of Athens
  • University General Hospital of Patras
  • Hippokration Hospital
  • Local Institution - 404
  • Soroka University Medical Centre
  • Rambam Health Corporation
  • HaEmek Medical Center
  • Shaare Zedek Medical Center
  • Hadassah Medical Center
  • Galilee Medical Center
  • Rabin Medical Center
  • Presidio Ospedaliero Antonio Perrino
  • Universita degli Studi di Cagliari - ASL8
  • Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
  • Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
  • Fondazione Ca Granda IRCCS Ospedale Maggiore
  • Seconda Universita Degli Studi Di Napoli
  • AORN A Cardarelli
  • Azienda Ospedaliero Universitaria S. Luigi Gonzaga
  • Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
  • Azienda Ospedaliera Universitaria Integrata Di Verona
  • Chronic Care Center
  • Hospital Sultanah Aminah
  • Hospital Sultanah Bahiyah
  • Hospital Raja Permaisuri Bainun
  • Queen Elizabeth Hospital
  • Hospital Umum Sarawak
  • University Malaya Medical Centre
  • Hospital Pulau Pinang c/o Penang Medical College
  • Changhua Christian Hospital
  • Kaohsiung Medical University Hospital
  • China Medical University Hospital
  • National Taiwan University Hospital
  • Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
  • Siriraj Hospital Mahidol University
  • Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
  • University Hospital Farhat Hached
  • Bone Marrow Transplant Center
  • Aziza Othmana Hospital
  • Military Hospital of Tunis
  • Acibadem Adana Hospital
  • Cukurova University Medical Faculty Balcali Hospital
  • Local Institution - 524
  • Hacettepe Universitesi
  • Antalya Egitim Arastirma
  • Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
  • Ege Universitesi Tip Fakultesi Hastanesi
  • Mersin University Medical Faculty
  • St James University Hospital
  • University College Hospital Trust
  • Barts Health NHS Trust - The Royal London Hospital
  • Whittington Hospital
  • Manchester Royal Infirmary

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Luspatercept (ACE-536) plus Best Supportive Care (BSC)

Placebo plus Best Supportive Care (BSC)

Arm Description

Luspatercept, subcutaneous(ly) (SC) once every 21 days

normal saline solution subcutaneous(ly) (SC) once every 21 days

Outcomes

Primary Outcome Measures

Percentage of Participants Who Achieved Erythroid Response - Week 13 to Week 24
Erythroid Response was defined as red blood cell (RBC) transfusion burden reduction from baseline ≥ 33% with a reduction of at least 2 units during Week 13 - 24 compared to the 12-week interval on or prior to Dose 1 Day 1.

Secondary Outcome Measures

Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - Week 37 to Week 48
Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 33% with a reduction of at least 2 units during Weeks 37 - 48 compared to the 12-week interval on or prior to Dose 1 Day 1.
Percentage Of Participants Who Achieve ≥ 50% Reduction From Baseline in Transfusion Burden - Week 13 to Week 24
Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 50% with a reduction of at least 2 units during Weeks 13 - 24 compared to the 12-week interval on or prior to Dose 1 Day 1.
Percentage Of Participants Who Achieve ≥ 50% Reduction From Baseline in Transfusion Burden - Week 37 to Week 48
Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 50% with a reduction of at least 2 units during Week 37 to Week 48 compared to the 12-week interval on or prior to Dose 1 Day 1.
Mean Change From Baseline in Transfusion Burden - Week 13 to Week 24
Baseline was defined as the total number of Red Blood Cells (RBC) units transfused during the 12-week interval on or prior to Dose 1 Day 1. This is compared to the total number of RBC units transfused during the 12-week interval from treatment weeks 13-24.
Mean Change From Baseline In Liver Iron Concentration (LIC) At Week 48
Baseline was defined as the last value on or before the first dose of study drug was administered; if multiple values were present for the same date, the average of these values was used. If a participant had 1 postbaseline assessment, it was used as the Week 48 value. If a participant had multiple postbaseline assessments, the last one was used as the Week 48 value. The value of LIC was collected by magnetic resonance imaging. Participants with a LIC value > 43 mg/g were not included in the analysis.
Mean Change From Baseline In Mean Daily Dose Of Iron Chelation Therapies (ICT) At Week 48
Three different types of Iron Chelation Therapy (ICT) were analyzed: 1. Deferasirox 2. Deferiprone 3. Deferoxamine Mesilate/Deferoxamine The baseline mean daily dose was calculated using the ICT dosage during the 12 weeks prior to first study drug administration and the postbaseline mean daily dose was calculated during the last 12 weeks of the 48-week double-blind Treatment Period or the last 12 weeks of the study treatment for early discontinued participants.
Mean Change From Baseline In Mean Serum Ferritin At Week 48
For each participant, the baseline mean serum ferritin level was calculated during the 12 weeks prior to first study drug administration. The postbaseline mean serum ferritin level was calculated during the last 12 weeks of the 48-week double-blind Treatment Period or last 12 weeks of study treatment, if discontinued early. The change was calculated as the difference of post baseline mean serum ferritin level and baseline mean serum ferritin level.
Mean Change From Baseline In Total Hip And Lumbar Spine Bone Mineral Density (BMD) At Week 48
For BMD, the lumbar spine and total hip were measured at baseline and 48 weeks by dual energy x-ray absorptiometry (DXA). Baseline was defined as the last value on or before the first dose of study drug is administered; if multiple values are present for the same date, the average of these values was used. If during the 48 week double-blinded treatment period, a participant has only one assessment, it is counted as 'Week 48' visit; if a participant has multiple assessments, the last one is used as 'Week 48' visit. The analysis was done on the population that had at least 2 measurements.
Mean Change From Baseline In Myocardial Iron At Week 48
Myocardial Iron levels were measured by Magnetic Resonance Imaging (MRI), using MRI parameter T2* (Unit: ms). T2* values correlates with heart failure (HF) risk (e.g. T2*<6ms: high HF risk).
Mean Change From Baseline in the Transfusion-dependent Quality of Life (TranQol) Questionnaire At Week 24
The TranQol is a self-administered quality of life tool developed for beta-thalassemia patients. The adult self-report version used in this study, includes 36 questions assessed on a 5-point response, that are grouped into 5 domains (Physical Health, Emotional Health, Sexual Health, Family Functioning, School/Career Functioning). Scores are calculated according to specific scoring algorithms developed by the authors. Both individual domains score and the total score range from 0 (worst) to 100 (best). Total Score and Physical Health domain score are reported. Positive change from baseline values indicate improvement.
Mean Change From Baseline in the 36-item Short Form Health Survey (SF-36) Questionnaire At Weeks 24
The SF-36 (version 2) is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. The raw score for each health domain is transformed into a 0 (worst) to 100 (best) domain score. The 0-100 scale score for each health domain is further converted to normbased scores using a T-score transformation, with a mean of 50 and a standard deviation (SD) of 10. Higher norm-based T-scores indicate better heath/QoL. The domains/summaries reported are: 1. Physical Functioning (Range of possible T-scores is 19.26 - 57.54) 2. General Health (Range of possible T-scores is 18.95 - 66.50) 3. Physical Component summary (PCS) (Range of possible T-scores is 5.02 - 79.78). Positive change from baseline values indicate improvement.
Number of Participants Who Utilized Healthcare Resources During Study
Number of participants who had any of the following types of Healthcare Resource Utilization (HRU): - a doctor office visit (non-study scheduled) - an emergency department visit - a hospitalization
Number of Days Spent in Higher Care Hospital Units
Types of hospitals units considered to be 'higher care' are: - Intensive Care Unit - Coronary Care Unit
Percentage Of Participants Who Were Transfusion Independent For ≥ 8 Weeks During Treatment
Transfusion independence was defined as the absence of any transfusion during any consecutive "rolling" 8-week time interval within the treatment period, i.e, Days 1 to 56, Days 2 to 57 and so on.
Duration of Reduction in Transfusion Burden
Responders were defined as subjects who achieved ≥ 33% reduction or ≥ 50% reduction in Red Blood Cells Transfusion (RBC-T) burden from baseline with a reduction of at least 2 RBC units during any rolling 12-week interval. The duration of reduction is calculated as Last Day of Response - First day of response +1
Longest Duration of Transfusion Independence
Transfusion independence was defined as the absence of any transfusion during any consecutive "rolling" 8-week time interval within the treatment period, ie, Days 1 to 56, Days 2 to 57 and so on. Longest duration of transfusion independence was estimated based on Kaplan-Meier model.
Time to Erythroid Response
Time to erythroid response was defined as the time from first dose of the study drug to first erythroid response. This is reported for participants with a ≥ 33% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) for any 12-week interval., as well as participants with a ≥ 50% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) for any 12-week interval.
Post-Baseline Transfusion Event Frequency
The number of transfusion events after start of study treatment were evaluated. For the definition of transfusion events, if multiple transfusions happen on the same date, they are counted as one event; if multiple transfusions happen on two consecutive dates, they are counted as one event; if multiple transfusions happen on three consecutive dates, they are counted as two events. Results are presented in 24-week intervals, up to 96 weeks after start of study treatment
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax)
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration at Steady State for the Starting Dose (Cmax,ss)
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Area Under the Concentration-Time Curve at Steady State for the Starting Dose (AUCss)
Participants With Treatment-Emergent Adverse Events (TEAE)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A serious AE is any AE occurring at any dose that - Results in death - Is life-threatening - Requires or prolongs existing inpatient hospitalization - Results in persistent or significant disability/incapacity - Is a congenital anomaly/birth defect - Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death
Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)
Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent."

Full Information

First Posted
October 21, 2015
Last Updated
March 23, 2023
Sponsor
Celgene
Collaborators
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
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1. Study Identification

Unique Protocol Identification Number
NCT02604433
Brief Title
An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Adults Who Require Regular Red Blood Cell Transfusions Due to Beta (β) Thalassemia
Acronym
BELIEVE
Official Title
A Phase 3, Double-Blind, Placebo Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) in Adults With Transfusion Dependent Beta (B)-Thalassemia
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
May 2, 2016 (Actual)
Primary Completion Date
January 5, 2021 (Actual)
Study Completion Date
January 5, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celgene
Collaborators
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) plus Best supportive care (BSC) versus placebo plus BSC in adults who require regular red blood cell transfusion due to (β)-thalassemia. The study is divided into the following periods: Historical Period, Screening/Run-in Period, Double-blind Treatment Period (48 weeks), Double-blind Long-term Treatment Period, (at the investigator's discretion an additional 48 weeks), Open-Label Phase post unblinding and upon Data Monitoring Committee positive recommendation Post-treatment Follow-up Period

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Erythrocyte Transfusion, Beta-Thalassemia
Keywords
ACE-536, Safety, Efficacy, Placebo, Red Blood Cell Transfusions, Beta -Thalassemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
336 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Luspatercept (ACE-536) plus Best Supportive Care (BSC)
Arm Type
Experimental
Arm Description
Luspatercept, subcutaneous(ly) (SC) once every 21 days
Arm Title
Placebo plus Best Supportive Care (BSC)
Arm Type
Placebo Comparator
Arm Description
normal saline solution subcutaneous(ly) (SC) once every 21 days
Intervention Type
Drug
Intervention Name(s)
Luspatercept
Other Intervention Name(s)
ACE-536
Intervention Description
Subjects will start with luspatercept at 1 mg/kg dose level.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo, Subcutaneous, every 21 days.
Primary Outcome Measure Information:
Title
Percentage of Participants Who Achieved Erythroid Response - Week 13 to Week 24
Description
Erythroid Response was defined as red blood cell (RBC) transfusion burden reduction from baseline ≥ 33% with a reduction of at least 2 units during Week 13 - 24 compared to the 12-week interval on or prior to Dose 1 Day 1.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24
Secondary Outcome Measure Information:
Title
Percentage Of Participants Who Achieved ≥ 33% Reduction From Baseline in Transfusion Burden - Week 37 to Week 48
Description
Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 33% with a reduction of at least 2 units during Weeks 37 - 48 compared to the 12-week interval on or prior to Dose 1 Day 1.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48
Title
Percentage Of Participants Who Achieve ≥ 50% Reduction From Baseline in Transfusion Burden - Week 13 to Week 24
Description
Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 50% with a reduction of at least 2 units during Weeks 13 - 24 compared to the 12-week interval on or prior to Dose 1 Day 1.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24
Title
Percentage Of Participants Who Achieve ≥ 50% Reduction From Baseline in Transfusion Burden - Week 37 to Week 48
Description
Percentage of participants who achieved a red blood cell (RBC) transfusion burden reduction from baseline ≥ 50% with a reduction of at least 2 units during Week 37 to Week 48 compared to the 12-week interval on or prior to Dose 1 Day 1.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48
Title
Mean Change From Baseline in Transfusion Burden - Week 13 to Week 24
Description
Baseline was defined as the total number of Red Blood Cells (RBC) units transfused during the 12-week interval on or prior to Dose 1 Day 1. This is compared to the total number of RBC units transfused during the 12-week interval from treatment weeks 13-24.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24
Title
Mean Change From Baseline In Liver Iron Concentration (LIC) At Week 48
Description
Baseline was defined as the last value on or before the first dose of study drug was administered; if multiple values were present for the same date, the average of these values was used. If a participant had 1 postbaseline assessment, it was used as the Week 48 value. If a participant had multiple postbaseline assessments, the last one was used as the Week 48 value. The value of LIC was collected by magnetic resonance imaging. Participants with a LIC value > 43 mg/g were not included in the analysis.
Time Frame
Baseline: Week -12 to Day -1; Treatment: Week 48
Title
Mean Change From Baseline In Mean Daily Dose Of Iron Chelation Therapies (ICT) At Week 48
Description
Three different types of Iron Chelation Therapy (ICT) were analyzed: 1. Deferasirox 2. Deferiprone 3. Deferoxamine Mesilate/Deferoxamine The baseline mean daily dose was calculated using the ICT dosage during the 12 weeks prior to first study drug administration and the postbaseline mean daily dose was calculated during the last 12 weeks of the 48-week double-blind Treatment Period or the last 12 weeks of the study treatment for early discontinued participants.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48
Title
Mean Change From Baseline In Mean Serum Ferritin At Week 48
Description
For each participant, the baseline mean serum ferritin level was calculated during the 12 weeks prior to first study drug administration. The postbaseline mean serum ferritin level was calculated during the last 12 weeks of the 48-week double-blind Treatment Period or last 12 weeks of study treatment, if discontinued early. The change was calculated as the difference of post baseline mean serum ferritin level and baseline mean serum ferritin level.
Time Frame
Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48
Title
Mean Change From Baseline In Total Hip And Lumbar Spine Bone Mineral Density (BMD) At Week 48
Description
For BMD, the lumbar spine and total hip were measured at baseline and 48 weeks by dual energy x-ray absorptiometry (DXA). Baseline was defined as the last value on or before the first dose of study drug is administered; if multiple values are present for the same date, the average of these values was used. If during the 48 week double-blinded treatment period, a participant has only one assessment, it is counted as 'Week 48' visit; if a participant has multiple assessments, the last one is used as 'Week 48' visit. The analysis was done on the population that had at least 2 measurements.
Time Frame
Baseline: Day 1; Treatment: Week 48
Title
Mean Change From Baseline In Myocardial Iron At Week 48
Description
Myocardial Iron levels were measured by Magnetic Resonance Imaging (MRI), using MRI parameter T2* (Unit: ms). T2* values correlates with heart failure (HF) risk (e.g. T2*<6ms: high HF risk).
Time Frame
Baseline: Day 1; Treatment: Week 48
Title
Mean Change From Baseline in the Transfusion-dependent Quality of Life (TranQol) Questionnaire At Week 24
Description
The TranQol is a self-administered quality of life tool developed for beta-thalassemia patients. The adult self-report version used in this study, includes 36 questions assessed on a 5-point response, that are grouped into 5 domains (Physical Health, Emotional Health, Sexual Health, Family Functioning, School/Career Functioning). Scores are calculated according to specific scoring algorithms developed by the authors. Both individual domains score and the total score range from 0 (worst) to 100 (best). Total Score and Physical Health domain score are reported. Positive change from baseline values indicate improvement.
Time Frame
Baseline: 4 weeks prior to Day 1; Treatment: Week 24
Title
Mean Change From Baseline in the 36-item Short Form Health Survey (SF-36) Questionnaire At Weeks 24
Description
The SF-36 (version 2) is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. The raw score for each health domain is transformed into a 0 (worst) to 100 (best) domain score. The 0-100 scale score for each health domain is further converted to normbased scores using a T-score transformation, with a mean of 50 and a standard deviation (SD) of 10. Higher norm-based T-scores indicate better heath/QoL. The domains/summaries reported are: 1. Physical Functioning (Range of possible T-scores is 19.26 - 57.54) 2. General Health (Range of possible T-scores is 18.95 - 66.50) 3. Physical Component summary (PCS) (Range of possible T-scores is 5.02 - 79.78). Positive change from baseline values indicate improvement.
Time Frame
Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24
Title
Number of Participants Who Utilized Healthcare Resources During Study
Description
Number of participants who had any of the following types of Healthcare Resource Utilization (HRU): - a doctor office visit (non-study scheduled) - an emergency department visit - a hospitalization
Time Frame
From informed consent signing (up to 12 weeks before start of treatment) to end of treatment (up to approximately 227 weeks)
Title
Number of Days Spent in Higher Care Hospital Units
Description
Types of hospitals units considered to be 'higher care' are: - Intensive Care Unit - Coronary Care Unit
Time Frame
From informed consent signing (up to 12 weeks before start of treatment) to end of treatment (up to approximately 227 weeks)
Title
Percentage Of Participants Who Were Transfusion Independent For ≥ 8 Weeks During Treatment
Description
Transfusion independence was defined as the absence of any transfusion during any consecutive "rolling" 8-week time interval within the treatment period, i.e, Days 1 to 56, Days 2 to 57 and so on.
Time Frame
From first dose through 3 weeks post last dose (up to approximately 218 weeks)
Title
Duration of Reduction in Transfusion Burden
Description
Responders were defined as subjects who achieved ≥ 33% reduction or ≥ 50% reduction in Red Blood Cells Transfusion (RBC-T) burden from baseline with a reduction of at least 2 RBC units during any rolling 12-week interval. The duration of reduction is calculated as Last Day of Response - First day of response +1
Time Frame
From first dose to end of study treatment (up to approximately 215 weeks)
Title
Longest Duration of Transfusion Independence
Description
Transfusion independence was defined as the absence of any transfusion during any consecutive "rolling" 8-week time interval within the treatment period, ie, Days 1 to 56, Days 2 to 57 and so on. Longest duration of transfusion independence was estimated based on Kaplan-Meier model.
Time Frame
From first dose through 3 weeks post last dose (up to approximately 218 weeks)
Title
Time to Erythroid Response
Description
Time to erythroid response was defined as the time from first dose of the study drug to first erythroid response. This is reported for participants with a ≥ 33% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) for any 12-week interval., as well as participants with a ≥ 50% reduction from baseline in RBC transfusion burden (with a reduction of at least 2 units) for any 12-week interval.
Time Frame
From first dose to 48 weeks following first dose
Title
Post-Baseline Transfusion Event Frequency
Description
The number of transfusion events after start of study treatment were evaluated. For the definition of transfusion events, if multiple transfusions happen on the same date, they are counted as one event; if multiple transfusions happen on two consecutive dates, they are counted as one event; if multiple transfusions happen on three consecutive dates, they are counted as two events. Results are presented in 24-week intervals, up to 96 weeks after start of study treatment
Time Frame
From first dose through 3 weeks post last dose (up to approximately 218 weeks)
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration at Steady State for the Starting Dose (Cmax,ss)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Pharmacokinetic (PK) Parameters: Bayesian Estimate of Area Under the Concentration-Time Curve at Steady State for the Starting Dose (AUCss)
Time Frame
Blood serum samples taken pre-dose and on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337
Title
Participants With Treatment-Emergent Adverse Events (TEAE)
Description
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A serious AE is any AE occurring at any dose that - Results in death - Is life-threatening - Requires or prolongs existing inpatient hospitalization - Results in persistent or significant disability/incapacity - Is a congenital anomaly/birth defect - Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death
Time Frame
From first dose to 90 days following last dose (up to approximately 52 months)
Title
Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA)
Description
Number of participants with positive ADA prior to taking study drug and/or during study. A participant was counted as "treatment-emergent" if there was a positive post-baseline sample while the baseline sample was ADA negative, or there was a positive post-baseline sample with a titer ≥ 4-fold of the baseline titer while the baseline sample was ADA positive. A participant was counted as "preexisting" if the baseline sample was ADA positive and the participant was not qualified for "treatment-emergent."
Time Frame
Timeframe: pre-dose, Day 1, Days 22, 64, 106, 148, 232, 316

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: Male or female, ≥18 years of age at the time of signing the informed consent document (ICF). Subject must understand and voluntarily sign an Inform Consent Form prior to any study-related assessments/procedures being conducted. Subject is willing and able to adhere to the study visit schedule and other protocol requirements. Documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia. (β-thalassemia with mutation and/or multiplication of alpha globin is allowed). Regularly transfused, defined as: 6-20 Red Blood Cell (RBC) units* in the 24 weeks prior to randomization and no transfusion-free period for ≥ 35 days during that period. * Sites who prescribe transfusions and have the transfusion records only in volumes should use for conversion of volume to units the below criteria, in order to obtain number of units within the last 24 weeks to assess the eligibility: 1 unit in this protocol refers to a quantity of packed RBCs approximately 200-350 mL. (i) sites who use transfusion bags within this range, or ≥ 350 mL, the conversion in units should be done by dividing the volume transfused to the patient by 350 mL, (ii) sites who use transfusion bags < 200 mL, the conversion in units should be done by dividing the volume transfused to the patient by 200 mL. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 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). FCBP participating in the study must: Have two 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 with, effective*** contraception without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks (approximately five times the mean terminal half-life of luspatercept based on multiple-dose Pharmacokinetic PK) data) after discontinuation of study therapy. True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. [Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.] *** Agreement to use highly effective methods of contraception that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly throughout the course of the study. Such methods include: Combined (estrogen and progesterone/progestin containing) hormonal contraception: Oral; Intravaginal; Transdermal; Progestogen/progestin only hormonal contraception associated with inhibition of ovulation: Oral; Injectable hormonal contraception; Implantable hormonal contraception; Placement of an intrauterine device (IUD); Placement of an intrauterine hormone-releasing system (IUS); Bilateral tubal occlusion; Vasectomized partner; Sexual Abstinence. Male subjects must: Practice true abstinence 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 five times the mean terminal half-life of luspatercept based on multiple-dose PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy. Exclusion Criteria: 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. A diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H); Evidence of active hepatitis C (HCV) infection as demonstrated by a positive HCV-RNA test of sufficient sensitivity, or active infectious hepatitis B as demonstrated by the presence of HBsAg and/or HBVDNA-positive,, or known positive human immunodeficiency virus (HIV). Note: Subjects receiving antiviral therapies should have 2 negative HCVRNA tests 3 months apart.(ie, one test at the end of the antiviral therapy and a second test 3 months following the first test). Deep Vein Thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to randomization. Use of chronic anticoagulant therapy is excluded, unless the treatment stopped at least 28 days prior to randomization. Anticoagulant therapies used for prophylaxis for surgery or high risk procedures as well as low Molecular Weight (LMW) heparin for superficial venous thrombosis and chronic aspirin are allowed. Platelet count > 1000 x 109/L Poorly controlled diabetes mellitus within 24 weeks prior to randomization as defined by short term (eg, hyperosmolar or ketoacidotic crisis) and/or history of diabetic cardiovascular complications (eg, stroke or myocardial infarction). Treatment with another investigational drug or device ≤ 28 days prior to randomization. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536). Use of an erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization. Iron chelation therapy, if initiated ≤ 24 weeks prior to randomization (allowed if initiated > 24 weeks before or during treatment). Hydroxyurea treatment ≤ 24 weeks prior to randomization. Pregnant or lactating females. Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤ Grade 1 according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (current active minor version). Major organ damage, including: Liver disease with alanine aminotransferase (ALT) > 3 x the upper limit of normal (ULN) or history of evidence of cirrhosis; 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 within 6 months of randomization. Lung disease, including pulmonary fibrosis or pulmonary hypertension which are clinically significant ie, ≥ Grade 3 NCI CTCAE version 4.0 (current active minor version). Creatinine clearance < 60 mL/min (per Cockroft-Gault formula). Proteinuria ≥ Grade 3 according to NCI CTCAE version 4.0 (current active minor version). Chronic systemic glucocorticoids ≤ 12 weeks prior to randomization (physiologic replacement therapy for adrenal insufficiency is allowed). Single day glucocorticoid treatment (eg, for prevention or treatment of transfusion reactions, 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). Cytotoxic agents, immunosuppressants ≤ 28 days prior to randomization (ie, antithymocite globulin (ATG) or cyclosporine) History of malignancy with the exception of: Curatively resected nonmelanoma skin cancer. Curatively treated cervical carcinoma in situ. Other solid tumor with no known active disease in the opinion of the investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital and Research Center at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Ann and Robert H Lurie Childrens Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Hospital of the University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Prince of Wales Hospital
City
Randwick
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Facility Name
Mater Hospital Brisbane
City
South Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Facility Name
Royal Adelaide Hospital Institute of Medical and Veterinary Science
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Monash Medical Centre
City
Clayton
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Facility Name
Sir Charles Gairdner Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
ZIP/Postal Code
2050
Country
Australia
Facility Name
University Mulitiprofile Hospital for Active Treatment Sveti Georgi EAD
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
Specialized Hospital for Active Treatment of Haematological Diseases - Sofia
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment Sveta Marina EAD
City
Varna
ZIP/Postal Code
9010
Country
Bulgaria
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
Hopital Henri Mondor
City
Creteil
ZIP/Postal Code
94010
Country
France
Facility Name
GH de Institut Catholique St. VincentHématologie
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Hopitaux de La Timone
City
Marseille Cedex 9
ZIP/Postal Code
13385
Country
France
Facility Name
Hospital of Necker
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Laiko General Hospital of Athens
City
Ampelokipi - Athens
ZIP/Postal Code
115 26
Country
Greece
Facility Name
Local Institution - 405
City
Ampelokipi - Athens
ZIP/Postal Code
115 26
Country
Greece
Facility Name
General Children's Hospital "Agia Sophia"
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
General Hospital Georgios Gennimatas of Athens
City
Athens
ZIP/Postal Code
11527
Country
Greece
Facility Name
University General Hospital of Patras
City
Rio Patras
ZIP/Postal Code
26500
Country
Greece
Facility Name
Hippokration Hospital
City
Thessaloniki
ZIP/Postal Code
54642
Country
Greece
Facility Name
Local Institution - 404
City
Thessaloniki
ZIP/Postal Code
54642
Country
Greece
Facility Name
Soroka University Medical Centre
City
Beer Sheva
ZIP/Postal Code
84101
Country
Israel
Facility Name
Rambam Health Corporation
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
HaEmek Medical Center
City
Haïfa (Afula)
ZIP/Postal Code
18101
Country
Israel
Facility Name
Shaare Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
91031
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Galilee Medical Center
City
Nahariya
ZIP/Postal Code
22100
Country
Israel
Facility Name
Rabin Medical Center
City
Petah Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Presidio Ospedaliero Antonio Perrino
City
Brindisi
ZIP/Postal Code
72100
Country
Italy
Facility Name
Universita degli Studi di Cagliari - ASL8
City
Cagliari
ZIP/Postal Code
09121
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant'Anna
City
Ferrara
ZIP/Postal Code
44124
Country
Italy
Facility Name
Ente Ospedaliero Ospedali Galliera - Centro della Microcitemia e delle Anemie Congenite
City
Genoa
ZIP/Postal Code
16128
Country
Italy
Facility Name
Fondazione Ca Granda IRCCS Ospedale Maggiore
City
Milan
ZIP/Postal Code
20122
Country
Italy
Facility Name
Seconda Universita Degli Studi Di Napoli
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
AORN A Cardarelli
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Azienda Ospedaliero Universitaria S. Luigi Gonzaga
City
Orbassano
ZIP/Postal Code
10043
Country
Italy
Facility Name
Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello
City
Palermo
ZIP/Postal Code
90146
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria Integrata Di Verona
City
Verona
ZIP/Postal Code
37134
Country
Italy
Facility Name
Chronic Care Center
City
Beirut
Country
Lebanon
Facility Name
Hospital Sultanah Aminah
City
Johor Bahru
State/Province
Johor
ZIP/Postal Code
80100
Country
Malaysia
Facility Name
Hospital Sultanah Bahiyah
City
Alor Setar
State/Province
Kedah
ZIP/Postal Code
05460
Country
Malaysia
Facility Name
Hospital Raja Permaisuri Bainun
City
Ipoh
State/Province
Perak
ZIP/Postal Code
30990
Country
Malaysia
Facility Name
Queen Elizabeth Hospital
City
Kota Kinabalu
State/Province
Sabah
ZIP/Postal Code
88586
Country
Malaysia
Facility Name
Hospital Umum Sarawak
City
Kuching
State/Province
Sarawak
ZIP/Postal Code
93586
Country
Malaysia
Facility Name
University Malaya Medical Centre
City
Kuala Lumpur
State/Province
Wilayah Persekutuan Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Hospital Pulau Pinang c/o Penang Medical College
City
Georgetown
ZIP/Postal Code
10990
Country
Malaysia
Facility Name
Changhua Christian Hospital
City
Changhua City
ZIP/Postal Code
500
Country
Taiwan
Facility Name
Kaohsiung Medical University Hospital
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
China Medical University Hospital
City
Taichung
ZIP/Postal Code
40447
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei, Zhongzheng Dist.
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Chulalongkorn University Faculty of Medicine - King Chulalongkorn Memorial Hospital
City
Bangkok
ZIP/Postal Code
10330
Country
Thailand
Facility Name
Siriraj Hospital Mahidol University
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Chiang Mai University - Maharaj Nakorn Chiang Mai Hospital
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand
Facility Name
University Hospital Farhat Hached
City
Sousse
ZIP/Postal Code
4031
Country
Tunisia
Facility Name
Bone Marrow Transplant Center
City
Tunis
ZIP/Postal Code
1006
Country
Tunisia
Facility Name
Aziza Othmana Hospital
City
Tunis
ZIP/Postal Code
1008
Country
Tunisia
Facility Name
Military Hospital of Tunis
City
Tunis
ZIP/Postal Code
1089
Country
Tunisia
Facility Name
Acibadem Adana Hospital
City
Adana
ZIP/Postal Code
01130
Country
Turkey
Facility Name
Cukurova University Medical Faculty Balcali Hospital
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Local Institution - 524
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Hacettepe Universitesi
City
Ankara
ZIP/Postal Code
01660
Country
Turkey
Facility Name
Antalya Egitim Arastirma
City
Antalya
ZIP/Postal Code
07100
Country
Turkey
Facility Name
Istanbul Universitesi Istanbul Tip Fakultesi Hastanesi
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi Hastanesi
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Mersin University Medical Faculty
City
Mersin
ZIP/Postal Code
33343
Country
Turkey
Facility Name
St James University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
University College Hospital Trust
City
London Bloomsbury
ZIP/Postal Code
WC1E 6AU
Country
United Kingdom
Facility Name
Barts Health NHS Trust - The Royal London Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
Whittington Hospital
City
London
ZIP/Postal Code
N19 5NF
Country
United Kingdom
Facility Name
Manchester Royal Infirmary
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
30504333
Citation
Porter J. Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361.
Results Reference
result
PubMed Identifier
30617198
Citation
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.
Results Reference
result
PubMed Identifier
33570654
Citation
Cappellini MD, Taher AT. The use of luspatercept for thalassemia in adults. Blood Adv. 2021 Jan 12;5(1):326-333. doi: 10.1182/bloodadvances.2020002725.
Results Reference
derived
PubMed Identifier
32212518
Citation
Cappellini MD, Viprakasit V, Taher AT, Georgiev P, Kuo KHM, Coates T, Voskaridou E, Liew HK, Pazgal-Kobrowski I, Forni GL, Perrotta S, Khelif A, Lal A, Kattamis A, Vlachaki E, Origa R, Aydinok Y, Bejaoui M, Ho PJ, Chew LP, Bee PC, Lim SM, Lu MY, Tantiworawit A, Ganeva P, Gercheva L, Shah F, Neufeld EJ, Thompson A, Laadem A, Shetty JK, Zou J, Zhang J, Miteva D, Zinger T, Linde PG, Sherman ML, Hermine O, Porter J, Piga A; BELIEVE Investigators. A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2020 Mar 26;382(13):1219-1231. doi: 10.1056/NEJMoa1910182.
Results Reference
derived
Links:
URL
https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
Description
BMS Clinical Trial Information
URL
https://www.bmsstudyconnect.com/s/US/English/USenHome
Description
BMS Clinical Trial Patient Recruiting
URL
https://www.fda.gov/Safety/MedWatch/SafetyInformation/default.htm
Description
FDA Safety Alerts and Recalls

Learn more about this trial

An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Adults Who Require Regular Red Blood Cell Transfusions Due to Beta (β) Thalassemia

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