Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02604433
Recruitment Status : Active, not recruiting
First Posted : November 13, 2015
Results First Posted : January 27, 2020
Last Update Posted : January 27, 2020
Sponsor:
Collaborator:
Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Celgene

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

Condition or disease Intervention/treatment Phase
Erythrocyte Transfusion Beta-Thalassemia Drug: Luspatercept Other: Placebo Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 336 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : May 2, 2016
Actual Primary Completion Date : November 24, 2017
Estimated Study Completion Date : June 7, 2025


Arm Intervention/treatment
Experimental: Luspatercept (ACE-536) plus Best Supportive Care (BSC)
Luspatercept, subcutaneous(ly) (SC) once every 21 days
Drug: Luspatercept
Subjects will start with luspatercept at 1 mg/kg dose level.
Other Name: ACE-536

Placebo Comparator: Placebo plus Best Supportive Care (BSC)
normal saline solution subcutaneous(ly) (SC) once every 21 days
Other: Placebo
Placebo, Subcutaneous, every 21 days.




Primary Outcome Measures :
  1. Percentage of Participants Who Achieved Erythroid Response From Week 13 to Week 24 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Weeks 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. Transfusion records collected up to a minimum of (death date, study discontinuation date, last dose date + 20 days or 11 May 2018) were used for the analysis.


Secondary Outcome Measures :
  1. Percentage Of Participants Who Achieve >=33% Reduction From Baseline in Transfusion Burden From Week 37 to Week 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Weeks 37 to Week 48 ]
    This hematological improvement outcome was defined as the 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. Transfusion records collected up to a minimum of (death date, study discontinuation date, last dose date + 20 days or 11 May 2018) were used for the analysis.

  2. Percentage Of Participants Who Achieve >=50% Reduction From Baseline in Transfusion Burden From Week 13 to Week 24 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24 ]
    This hematological improvement outcome was defined as the 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. Transfusion records collected up to a minimum of (death date, study discontinuation date, last dose date + 20 days or 11 May 2018) were used for the analysis.

  3. Percentage Of Participants Who Achieve >=50% Reduction From Baseline in Transfusion Burden From Week 37 to Week 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48 ]
    This hematological improvement outcome was defined as the 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. Transfusion records collected up to a minimum of (death date, study discontinuation date, last dose date + 20 days or 11 May 2018) were used for the analysis.

  4. Baseline Values and Mean Change From Baseline in Transfusion Burden (RBC Units) to the Fixed Week 13 to Week 24 Interval (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Weeks 13 to Week 24 ]
    Baseline was defined as the total number of 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.

  5. Baseline Values and Mean Change From Baseline At Week 48 In Derived Liver Iron Concentration (LIC) By Magnetic Resonance Imaging (MRI) (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Week -12 to Day -1; Treatment: Week 48 ]
    In β-thalassemia adult patients who are transfused, iron overload occurs mainly as a result of accumulation of iron from transfusions and, to a lesser extent, increased intestinal absorption of iron due to hepcidin suppression. 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 either the value collected from the electronic case report form or the value derived from the T2*, R2*, or R2 parameter, depending on which techniques and software were used for magnetic resonance imaging LIC acquisition. Participants with an LIC value > 43 mg/g were not included in the analysis.

  6. Baseline Values and Mean Change From Baseline At Week 48 In Mean Daily Dose Of Iron Chelation Therapies (ICT) Deferasirox, Deferiprone and Deferoxamine Mesilate/Deferoxamine (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Week 37 to Week 48 ]
    This outcome tests the hypothesis that reducing the transfusion burden will likely reduce ICT daily dosage requirements, which will provide a number of benefits to the participants. 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. DM/D = Deferoxamine Mesilate / Deferoxamine

  7. Baseline Values and Mean Change From Baseline At Week 48 In Mean Serum Ferritin (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day -83 to Day 1; Treatment: Week 37 to 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.

  8. Baseline Values and Mean Change From Baseline In Total Hip And Lumbar Spine Bone Mineral Density (BMD) At Week 48 By Dual Energy X-Ray Absorptiometry (DXA) (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day 1; Treatment: 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.

  9. Baseline Values and Mean Change From Baseline In Myocardial Iron By T2* Magnetic Resonance Imaging (MRI) at Week 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: Day 1; Treatment: Week 48 ]
    MRI parameter T2* (Unit: ms) is considered as the most reliable way to assess cardiac iron overload and heart failure (HF) risk compared to other methods in Beta-Thalassemia patients, clinical management being nowadays based on it (e.g. T2*<6ms: high HF risk)

  10. Baseline Values and Mean Change From Baseline in the Transfusion-dependent Quality of Life (TranQol) Questionnaire Total Score at Weeks 24 and 48 [ Time Frame: Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24 and 48 ]
    The TranQol is a disease-specific, self-administered, well-validated health-related 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 author's guidelines and scoring rules. The total score ranges from 0 (worst) to 100 (best). The TranQoL was considered completed at a given visit when ≥ 75% of all items were answered (ie, ≥ 27 items of the 36 items or a nonmissing total score). Positive change from baseline values indicate improvement.

  11. Baseline Values and Mean Change From Baseline in the Transfusion-dependent Quality of Life (TranQol) Questionnaire Physical Health Domain at Weeks 24 and 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24 and 48 ]
    The TranQol is a disease-specific, self-administered, well-validated health-related quality of life tool developed for beta-thalassemia patients. The adult self-report version used in this study, includes 10 questions concerning physical assessed on a 5-point response scale. Scores are calculated according to author's guidelines and scoring rules. The Physical Health Domain ranges from 0 (worst) to 100 (best). The TranQoL was considered completed at a given visit when ≥ 75% of all items were answered (ie, ≥ 27 items of the 36 items or a nonmissing total score). Positive change from baseline values indicate improvement.

  12. Baseline Values and Mean Change From Baseline in the 36-item Short Form Health Survey (SF-36) Questionnaire Physical Functioning Domain at Weeks 24 and 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24 and 48 ]
    The SF-36 is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. Survey items 3a-3j comprise the Physical Functioning domain which is reported here. 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, based on data from a nationally representative sample of adults from the US. The range of possible T-scores for the Physical Functioning domain is 19.26 - 57.54 and the minimally important differences between readings is considered 3.0. The completion of the SF-36 for a given visit was defined as ≥ 50% of all items being answered (ie, ≥ 18 items of the 36 items). Positive change from baseline values indicate improvement.

  13. Baseline Values and Mean Change From Baseline in the 36-item Short Form Health Survey (SF-36) Questionnaire General Health Domain at Weeks 24 and 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24 and 48 ]
    The SF-36 is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. Survey items 1, 11a-11d comprise the General Health domain which is reported here. 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 norm-based 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, based on data from a nationally representative sample of adults from the US. The range of possible T-scores for the General Health domain is 18.95 - 66.50 and the minimally important differences between readings is considered 2.0. The completion of the SF-36 for a given visit was defined as ≥ 50% of all items being answered (ie, ≥ 18 items of the 36 items). Positive change from baseline values indicate improvement.

  14. Baseline Values and Mean Change From Baseline in the 36-item Short Form Health Survey (SF-36) Questionnaire Physical Component Summary at Weeks 24 and 48 (Data Cut-off Date: 11 May 2018) [ Time Frame: Baseline: 4 weeks prior to Day 1; Treatment: Weeks 24 and 48 ]
    The SF-36 is a generic, self-administered instrument consisting of 8 multi-item scales that assess 8 health domains. The Physical Component Summary is one of two summary scales that summarize information from the 8 health scales. This information is also converted to norm-based 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, based on data from a nationally representative sample of adults from the US. The range of possible T-scores for the Physical Component Summary is 5.02 - 79.78 and the minimally important differences between readings is considered 2.0. The completion of the SF-36 for a given visit was defined as ≥ 50% of all items being answered (ie, ≥ 18 items of the 36 items). Positive change from baseline values indicate improvement.

  15. Percentage of Participants Who Utilized Healthcare Resources During Treatment [Healthcare Resource Utilization (HRU)] (Data Cut-off Date: 11 May 2018) [ Time Frame: HRU data is collected continuously from Week-12 (informed consent) up to 9 weeks post last dose. Up to data cutoff date of 11 May 2018 (48 weeks post last participant enrolled day 1), median exposure is 64.1 weeks (Q1,Q3:52.5,70.0; Min, Max: 3,97) ]
    Percentage of participants who had a doctor office visit (non-study scheduled), or emergency room visit, or a hospitalization after signing informed consent.

  16. Number of Days in Higher Care Hospital Units; [Healthcare Resource Utilization (HRU)] (Data Cut-off Date: 11 May 2018) [ Time Frame: HRU data is collected continuously from Week-12 (informed consent) up to 9 weeks post last dose. Up to data cutoff date of 11 May 2018 (48 weeks post last participant enrolled day 1), median exposure is 64.1 weeks (Q1,Q3:52.5,70.0; Min, Max: 3,97) ]
    Types of hospitals units considered to be 'higher care' are - Intensive Care Unit - Coronary Care Unit

  17. Percentage Of Participants Who Were Transfusion Independent For ≥ 8 Weeks During Treatment (Data Cut-off Date: 11 May 2018) [ Time Frame: Transfusion data is collected continuously at week (wk) -24 (12 weeks pre ICF) up to 9 wks post last dose. Efficacy cutoff = defined as: death, study discontinuation, last dose+20, 11 May 18; median exposure is 64.1 wks (Q1, Q3: 52.5,70.0; Min, Max: 3,97) ]
    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. Participants discontinued from double-blind treatment for lack of therapeutic effect or with less than 56 days of assessment during the double-blind treatment period were counted as nonresponders. Transfusion records were collected up to a minimum of (death date, or study discontinuation date, or last dose date + 20 days, or 11 May 2018) were used for the analysis.

  18. Mean Duration of Reduction in Transfusion Burden In Participants With a >= 33% Reduction and >=50% Reduction in Red Blood Cell (RBC) Transfusion Burden During Any Rolling 12-week Interval Up to the Efficacy Cutoff Date (11 May 2018) [ Time Frame: Transfusion data is collected continuously at week (wk) -24 (12 weeks pre ICF) up to 9 wks post last dose. Efficacy cutoff = defined as: death, study discontinuation, last dose+20, 11 May 18; median exposure is 64.1 wks (Q1, Q3: 52.5,70.0; Min, Max: 3,97) ]
    The duration of response was defined as Last Day of Response - First Day of Response + 1. For participants who continued to respond at the efficacy cutoff, the end day of the response was censored at the date of efficacy cutoff and the duration of response was calculated as date of efficacy cutoff - first day of response + 1 day. The efficacy cutoff date was defined as the minimum date among death date, study discontinuation date, last dose date + 20, and 11 May 2018. The response of transfusion burden reduction was assessed based on rolling method.

  19. Kaplan-Meier Estimates for Duration of Transfusion Independence in Participants Who Were Transfusion Independent For ≥ 8 Weeks (Data Cut-off Date: 11 May 2018) [ Time Frame: Transfusion data is collected continuously at week (wk) -24 (12 weeks pre ICF) up to 9 wks post last dose. Efficacy cutoff = defined as: death, study discontinuation, last dose+20, 11 May 18; median exposure is 64.1 wks (Q1, Q3: 52.5,70.0; Min, Max: 3,97) ]
    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. Participants discontinued from double-blind treatment for lack of therapeutic effect or with less than 56 days of assessment during the double-blind treatment period were counted as nonresponders.

  20. Time to Erythroid Response in Participants With ≥ 33% Reduction and ≥ 50% Reduction in RBC Transfusion Burden (Data Cut-off Date: 11 May 2018) [ Time Frame: Transfusion data is collected continuously at week (wk) -24 (12 weeks pre ICF) up to 9 wks post last dose. Efficacy cutoff = defined as: death, study discontinuation, last dose+20, 11 May 18; median exposure is 64.1 wks (Q1, Q3: 52.5,70.0; Min, Max: 3,97) ]
    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.

  21. Post-Baseline Transfusion Event Frequency (Data Cut-off Date: 11 May 2018) [ Time Frame: Transfusion data is collected continuously at week (wk) -24 (12 weeks pre ICF) up to 9 wks post last dose. Efficacy cutoff = defined as: death, study discontinuation, last dose+20, 11 May 18; median exposure is 64.1 wks (Q1, Q3: 52.5,70.0; Min, Max: 3,97) ]
    The number of transfusion events were evaluated, as these relate directly to hours or days devoted to receiving RBC transfusions that can impact patients' quality of life. 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. Events are counted while on while on treatment inclusive of 3 weeks after the last treatment.

  22. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Clearance (CL/F) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  23. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Apparent Volume of Distribution of the Central Compartment (V1/F) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  24. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Elimination Half-life (t1/2) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  25. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Time to Reach Maximum Concentration (Tmax) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  26. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration for the Starting Dose (Cmax) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  27. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Maximum Concentration at Steady State for the Starting Dose (Cmax,ss) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  28. Pharmacokinetic (PK) Parameters: Bayesian Estimate of Area Under the Concentration-Time Curve at Steady State for the Starting Dose (AUCss) (Data Cut-off Date: 11 May 2018) [ Time Frame: Blood serum samples taken pre-dose on Days 1, 22, 64, 85, 106, 127, 169, 211, 253, 295, 337. Blood serum samples also taken on Days 135 and 142 (Days 8 + 15 after Dose 6) ]
  29. Participants With Treatment-Emergent Adverse Events (TEAE) (Data Cut-off Date: 11 May 2018) [ Time Frame: Day 1 up to 97 weeks (maximum treatment as of data cut-off date) ]
    An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE includes AEs between the first dose date of either study drug and 90 days after the last dose of study drug. 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

  30. Participants With Pre-Existing and/or Treatment-Emergent Antidrug Antibodies (ADA) (Data Cut-off Date: 11 May 2018) [ Time Frame: Timeframe: predose Day 1, Days 22, 64, 106, 148, 232, 316 ]
    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."



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02604433


Locations
Show Show 73 study locations
Sponsors and Collaborators
Celgene
Acceleron Pharma, Inc.
Investigators
Layout table for investigator information
Study Director: Jeevan Shetty, MBCh.B, FRCP Celgene Corporation
  Study Documents (Full-Text)

Documents provided by Celgene:
Study Protocol  [PDF] December 11, 2018
Statistical Analysis Plan  [PDF] June 19, 2018

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02604433    
Other Study ID Numbers: ACE-536-B-THAL-001
First Posted: November 13, 2015    Key Record Dates
Results First Posted: January 27, 2020
Last Update Posted: January 27, 2020
Last Verified: January 2020
Keywords provided by Celgene:
ACE-536
Safety
Efficacy
Placebo
Red Blood Cell Transfusions
Beta -Thalassemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn