B-Thalassemia
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics, of ascending doses of luspatercept in participants with β-thalassemia. The primary objective of this study is to evaluate erythroid response, defined as: 1. a hemoglobin increase of ≥ 1.5 g/dL from baseline for ≥ 14 days (in the absence of red blood cell \[RBC\] transfusions) in non-transfusion dependent participants, or 2. a ≥ 20% reduction in RBC transfusion burden compared to pretreatment in transfusion dependent participants.
Interventions
DRUGluspatercept
subcutaneous injection
Sponsors
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Men or women ≥18 years of age * For the dose escalation phase of the study: documented diagnosis of β-thalassemia intermedia (transfusion dependent participants must not have begun regular transfusions at age \<4.0 years). For the expansion cohort: documented diagnosis of β-thalassemia (including β-thalassemia major or β-thalassemia intermedia) * Prior splenectomy or spleen size \<18 cm in the longest diameter by abdominal ultrasound (dose escalation cohorts only) * Anemia, defined as: (1) mean hemoglobin concentration \<10.0 g/dL of 2 measurements (one performed within one day prior to Cycle 1 Day 1 and the other performed during the screening period \[Day -28 to Day -1\]) in non-transfusion dependent participants, defined as having received \< 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1, or (2) transfusion dependent participants, defined as requiring ≥ 4 units of RBCs every 8 weeks (confirmed over 6 months prior to Cycle 1 Day 1) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \<3 x upper limit of normal (ULN) * Serum creatinine ≤1.5 x ULN * Adequate pregnancy avoidance measures * Participants are able to adhere to the study visit schedule, understand, and comply with all protocol requirements * Understand and able to provide written informed consent Key
Exclusion criteria
* Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic, gastrointestinal, infectious, immunological (including clinically significant allo- or auto-immunization) or genitourinary disease considered by the investigator as not adequately controlled prior to Cycle 1 Day 1 * Folate deficiency * Symptomatic splenomegaly * Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B virus (HBV) or active infectious hepatitis C virus (HCV) * Known history of thromboembolic events ≥Grade 3 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 (current active minor version) * Ejection fraction \<50% by echocardiogram, multi-gated acquisition scan (MUGA), or cardiac magnetic resonance imaging (MRI) * Uncontrolled hypertension defined as systolic blood pressure (BP) ≥150 mm Hg or diastolic BP ≥95 mm Hg * Heart failure class 3 or higher (New York Heart Association \[NYHA\]) * QTc \>450 msec on screening electrocardiogram (ECG) * Platelet count \<100 x10\^9/L or \>1,000 x10\^9/L * Proteinuria ≥Grade 2 * Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1 * Treatment with another investigational drug or device, or approved therapy for investigational use ≤28 days prior to Cycle 1 Day 1, or if the half-life of the previous investigational product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer * Transfusion event within 7 days prior to Cycle 1 Day 1 * Participants receiving or planning to receive hydroxyurea treatment. Participants must not have had hydroxyurea within 90 days of Cycle 1 Day 1 * Splenectomy within 56 days prior to Cycle 1 Day 1 * Major surgery (except splenectomy) within 28 days prior to Cycle 1 Day 1. Participants must have completely recovered from any previous surgery prior to Cycle 1 Day 1 * Iron chelation therapy initiated within 56 days prior to Cycle 1 Day 1 * Cytotoxic agents, systemic corticosteroids, immunosuppressants, or anticoagulant therapy such as warfarin or heparin within 28 days prior to Cycle 1 Day 1 (prophylactic aspirin up to 100 mg/day is permitted) * Pregnant or lactating women * History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug * Prior treatment with sotatercept (ACE-011) or luspatercept (ACE-536)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | Up to approximately 20 weeks | An erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days in the absence of blood transfusion. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days is presented. |
| Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 weeks) | Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during a 12-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 12 weeks prior to the start of treatment (baseline). The interval during the pretreatment period was defined as the 12 weeks prior to the first dose of study drug. An interval during the treatment plus follow-up period was defined as any 12-week interval after the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of participants with a ≥20% reduction in RBC transfusion burden from baseline is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | Up to approximately 20 weeks | AEs were graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) and graded as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences; and Grade 5=death related to AE. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experienced an AE of ≥Grade 3 is presented. |
| Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | Up to approximately 12 weeks | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who discontinued study treatment due to an AE is presented. |
| Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | Up to 28 days | DLTs were determined using the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) and graded as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences; and Grade 5=death related to AE. The occurrence of any of the following toxicities occurring up to 28 days after the first dose was considered a DLT: treatment-related serious adverse event (SAE) ≥ Grade 3; treatment related non-hematologic adverse event (AE) ≥ Grade 3; and treatment related hematologic AE ≥ Grade 4. The number of participants who experienced a DLT is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | Any 8-week interval during the study (up to approximately 20 Weeks) | A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.0 g/dL from baseline during an 8-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. An 8-week interval was defined as any consecutive 8 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.0 g/dL from baseline is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | Any 8-week interval during the study (up to approximately 20 Weeks) | A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline during an 8-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. An 8-week interval was defined as any consecutive 8 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 Weeks) | A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.0 g/dL from baseline during a 12-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. A 12-week interval was defined as any consecutive 12 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.0 g/dL from baseline is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 Weeks) | A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline during a 12-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. A 12-week interval was defined as any consecutive 12 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline is presented. |
| Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval | Any 8-week interval during the study (up to approximately 20 weeks) | Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during an 8-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 8 weeks prior to the start of treatment (baseline). TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). An 8-week interval was defined as any consecutive 8 weeks during the study. The percentage of participants with a ≥50% reduction in RBC transfusion burden from baseline is presented. |
| Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 weeks) | Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during a 12-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 12 weeks prior to the start of treatment (baseline). TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). A 12-week interval was defined as any consecutive 12 weeks during the study. The percentage of participants with a ≥50% reduction in RBC transfusion burden from baseline is presented. |
| Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks | Any 8-week interval during the study (up to approximately 20 weeks) | Transfusion independence for TD participants was defined as the percentage of participants who did not require RBC transfusion units (or milliliters) transfused for ≥8 weeks in the study after start of treatment. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of participants who maintained transfusion independence for ≥8 weeks is presented. |
| Time To Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval by Pooled Dose Groups | Any 12-week interval during the study (up to approximately 20 weeks) | Time to erythroid response was defined as the time from first dose to the first date of any rolling 12-week window achieving a hemoglobin increase ≥1.0 g/dL. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The time to the first date of any rolling 12-week window achieving a hemoglobin increase ≥1.0 g/dL is presented. |
| Time To Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 weeks) | Time to erythroid response was defined as the time from the first dose to the first date of any rolling 12-week window achieving a red blood cell (RBC) transfusion burden reduction of ≥50% compared to pretreatment. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The time to the first date of any rolling 12-week window achieving a red blood cell transfusion burden reduction of ≥50% compared to pretreatment is presented. |
| Duration of Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 weeks) | Duration of erythroid response was defined as the time from the first rolling 12-week window achieving a hemoglobin increase of ≥1.0 g/dL to the date of the last consecutive rolling 12-week window achieving a hemoglobin increase of ≥1.0 g/dL. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The duration of response for participants achieving a hemoglobin increase ≥1.0 g/dL is presented. |
| Duration of Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% During a Rolling 12-week Interval | Any 12-week interval during the study (up to approximately 20 weeks) | Duration of erythroid response was defined as the time from the first rolling 12-week window achieving a red blood cell (RBC) transfusion burden reduction of ≥50% compared to pretreatment to the last consecutive rolling 12-week window achieving a RBC transfusion burden reduction of ≥50% compared to pretreatment. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The duration of response for participants achieving a RBC transfusion burden reduction of ≥50% compared to pretreatment is presented. |
| Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine BSAP. The percent change from baseline in BSAP was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine CTX. The percent change from baseline in CTX was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Serum Iron | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine serum iron. The percent change from baseline in serum iron was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine TIBC. The percent change from baseline in TIBC was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Transferrin | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine transferrin. The percent change from baseline in transferrin was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine soluble transferrin receptor. The percent change from baseline in soluble transferrin receptor was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Ferritin | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine ferritin. The percent change from baseline in ferritin was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to Day 113 in Serum Non-transferrin Bound Iron (NTBI) | Baseline (prior to first dose of study drug) and Day 113 | Blood samples were to be collected at pre-specified time intervals to determine NTBI. Baseline was pre-specified to be the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to Day 113 in Calculated Transferrin Saturation | Baseline (prior to first dose of study drug) and Day 113 | The calculated transferrin saturation is the ratio of the serum iron concentration and the total iron binding capacity (TIBC) expressed as a percentage. Blood samples were to be collected at pre-specified time intervals for serum iron and TIBC to determine the calculated transferrin saturation. Baseline was pre-specified to be the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hepcidin | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine hepcidin. The percent change from baseline in hepcidin was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Reticulocytes | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine reticulocytes. The percent change from baseline in reticulocytes was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Erythropoietin | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine erythropoietin. The percent change from baseline in erythropoietin was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine nRBC count. The percent change from baseline in nRBC count was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine Hb A. The percent change from baseline in Hb A was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine Hb A2. The percent change from baseline in Hb A2 was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine Hb C. The percent change from baseline in Hb C was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine Hb D. The percent change from baseline in Hb D was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine Hb F. The percent change from baseline in Hb F was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Gamma Globin Gene | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine gamma globin gene. The percent change from baseline in gamma globin gene was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Haptoglobin | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine haptoglobin. The percent change from baseline in haptoglobin was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine Hb S. The percent change from baseline in Hb S was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Alpha Globin Gene | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine alpha globin gene. The percent change from baseline in alpha globin gene was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Beta Globin Gene | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine beta globin gene. The percent change from baseline in beta globin gene was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Indirect Bilirubin | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine indirect bilirubin. The percent change from baseline in indirect bilirubin was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine LDH. The percent change from baseline in LDH was measured. Baseline was the last measurement prior to the first dose of study drug. |
| Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC <3 mg/g Dry Weight | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for NTD participants with baseline LIC \<3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The change from baseline to Day 113 in mean LIC for NTD participants with baseline LIC \<3 mg/g dry weight is presented. |
| Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for NTD participants with baseline LIC ≥3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The change from baseline to Day 113 in mean LIC for NTD participants with baseline LIC ≥3 mg/g dry weight is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | End of Treatment (up to Day 113) | LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in NTD participants with a baseline LIC of ≥3 mg/g dry weight. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of NTD participants with baseline LIC ≥3 mg/g dry weight who have demonstrated an LIC response is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | End of Treatment (up to Day 113) | LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in NTD participants with a baseline LIC of ≥3 mg/g dry weight and who have used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of NTD participants with baseline LIC ≥3 mg/g dry weight, who have used ICT, and who have demonstrated an LIC response is presented. |
| Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | End of Treatment (up to Day 113) | LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in NTD participants with a baseline LIC of ≥3 mg/g dry weight and who have not used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of NTD participants with baseline LIC ≥3 mg/g dry weight, who have not used ICT, and who have demonstrated an LIC response is presented. |
| Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC <3 mg/g Dry Weight | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for TD participants with baseline LIC \<3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The change from baseline to Day 113 in mean LIC for TD participants with baseline LIC \<3 mg/g dry weight is presented. |
| Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight | Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113) | Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for TD participants with baseline LIC ≥3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The change from baseline to Day 113 in mean LIC for TD participants with baseline LIC ≥3 mg/g dry weight is presented. |
| Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | End of Treatment (up to Day 113) | LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in TD participants with a baseline LIC of ≥3 mg/g dry weight. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of TD participants with baseline LIC ≥3 mg/g dry weight who have demonstrated an LIC response is presented. |
| Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | End of Treatment (up to Day 113) | LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in TD participants with a baseline LIC of ≥3 mg/g dry weight and who have used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of TD participants with baseline LIC ≥3 mg/g dry weight, who have used ICT, and who have demonstrated an LIC response is presented. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 20 weeks | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experienced an AE is presented. |
| Maximum Concentration (Cmax) of Luspatercept | Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Day 1 | Blood samples were collected at specified intervals for the determination of Cmax. Cmax was defined as the maximum concentration of luspatercept observed after administration. Cmax was based on non-compartmental analysis. |
| Time to Maximum Concentration (Tmax) of Luspatercept | Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Day 1 | Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as the time to maximum concentration of luspatercept observed after administration. Tmax was based on non-compartmental analysis. |
| Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | Cycle 1: Days 1, 8, 11, and 15; Day 22 (Cycle 2 Day 1). Cycles 1 and 2 are 21-day cycles | Blood samples were collected at specified intervals for the determination of AUC0-21. AUC0-21 was defined as the area under the concentration time curve of luspatercept from time zero to Day 21. AUC0-21 was based on non-compartmental analysis and calculated by the linear trapezoidal method. |
| Terminal Elimination Half Life (t½) of Luspatercept | Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Days 1 and 8; Cycles 4 and 5 (21-day cycles): Days 1, 8, and 15; study follow-up on Days 113, 141, and 169 | Blood samples were collected at specified intervals for the determination of t½. t½ was defined as the time required to divide the serum concentration of luspatercept by two after reaching pseudo-equilibrium. t½ was based on non-compartmental analysis. |
| Apparent Terminal Rate Constant (Lambda z) of Luspatercept | Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Days 1 and 8; Cycles 4 and 5 (21-day cycles): Days 1, 8, and 15; study follow-up on Days 113, 141, and 169 | Blood samples were collected at specified intervals for the determination of apparent terminal rate constant. Apparent terminal rate constant was defined as the amount of luspatercept that was eliminated from the body during a given period of time and was calculated by linear regression of the terminal portion of the log-concentration-time curve in serum. Apparent terminal rate constant was based on non-compartmental analysis. |
| Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | End of Treatment (up to Day 113) | LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in TD participants with a baseline LIC of ≥3 mg/g dry weight and who have not used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of TD participants with baseline LIC ≥3 mg/g dry weight, who have not used ICT, and who have demonstrated an LIC response is presented. |
| Number of Participants Who Experienced a Serious Adverse Event (SAE) | Up to approximately 20 weeks | An SAE was any adverse event, occurring at any dose level/regimen and regardless of causality that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or was an important medical event. The number of participants who experienced an SAE is presented. |
Countries
Greece, Italy
Participant flow
Recruitment details
Participants from the study A536-04 were eligible to be initiated in extension study A536-06 (NCT02268409) following the last dose of luspatercept. Participants did not undergo an end of study visit in study A536-04 but instead were initiated immediately into the extension study.
Participants by arm
| Arm | Count |
|---|---|
| Luspatercept 0.2 mg/kg Participants received luspatercept 0.2 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). | 6 |
| Luspatercept 0.4 mg/kg Participants received luspatercept 0.4 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). | 6 |
| Luspatercept 0.6 mg/kg Participants received luspatercept 0.6 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). | 6 |
| Luspatercept 0.8 mg/kg Participants received luspatercept 0.8 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). | 6 |
| Luspatercept 1.0 mg/kg Participants received luspatercept 1.0 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). | 6 |
| Luspatercept 1.25 mg/kg Participants received luspatercept 1.25 mg/kg as an SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days). | 5 |
| Expansion Cohort Participants received an initial dose of luspatercept 0.8 mg/kg as an SC injection on Day 1 of Cycle 1 (Cycle length = 21 days). For each subsequent cycle (up to 5 cycles), the dose was titrated up to a maximum dose of 1.25 mg/kg based on the safety review team (SRT) recommendations. | 29 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Initiated into extension study A536-06 | 0 | 0 | 0 | 0 | 0 | 2 | 24 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Luspatercept 0.2 mg/kg | Luspatercept 0.4 mg/kg | Luspatercept 0.6 mg/kg | Luspatercept 0.8 mg/kg | Luspatercept 1.0 mg/kg | Luspatercept 1.25 mg/kg | Expansion Cohort |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.1 Years STANDARD_DEVIATION 10.5 | 37.3 Years STANDARD_DEVIATION 11.3 | 32.0 Years STANDARD_DEVIATION 7.1 | 39.2 Years STANDARD_DEVIATION 12.4 | 33.2 Years STANDARD_DEVIATION 10.3 | 40.8 Years STANDARD_DEVIATION 11.9 | 42.8 Years STANDARD_DEVIATION 7.9 | 38.9 Years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 64 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 62 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Female | 31 Participants | 4 Participants | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 13 Participants |
| Sex: Female, Male Male | 33 Participants | 2 Participants | 5 Participants | 4 Participants | 1 Participants | 4 Participants | 1 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 29 |
| other Total, other adverse events | 5 / 6 | 6 / 6 | 5 / 6 | 6 / 6 | 6 / 6 | 5 / 5 | 25 / 29 |
| serious Total, serious adverse events | 0 / 6 | 1 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 5 | 0 / 29 |
Outcome results
Primary
Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days
An erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days in the absence of blood transfusion. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days is presented.
Time frame: Up to approximately 20 weeks
Population: All participants who received ≥1 dose of study treatment and received \<4 units of RBCs within 8 weeks prior to the first dose of study drug and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 0.0 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 0.0 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 0.0 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 66.7 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline for ≥14 Days | 60.0 Percentage of participants |
Primary
Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval
Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during a 12-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 12 weeks prior to the start of treatment (baseline). The interval during the pretreatment period was defined as the 12 weeks prior to the first dose of study drug. An interval during the treatment plus follow-up period was defined as any 12-week interval after the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of participants with a ≥20% reduction in RBC transfusion burden from baseline is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug) and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.6 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 100 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 66.7 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 100 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 75.0 Percentage of participants |
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants With a ≥20% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 78.9 Percentage of participants |
Secondary
Apparent Terminal Rate Constant (Lambda z) of Luspatercept
Blood samples were collected at specified intervals for the determination of apparent terminal rate constant. Apparent terminal rate constant was defined as the amount of luspatercept that was eliminated from the body during a given period of time and was calculated by linear regression of the terminal portion of the log-concentration-time curve in serum. Apparent terminal rate constant was based on non-compartmental analysis.
Time frame: Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Days 1 and 8; Cycles 4 and 5 (21-day cycles): Days 1, 8, and 15; study follow-up on Days 113, 141, and 169
Population: The analysis population consisted of all participants who received ≥1 dose of luspatercept and who had available data for the analysis of apparent terminal rate constant.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.06 1/Day | Geometric Coefficient of Variation 27.52 |
| Luspatercept 0.4 mg/kg | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.07 1/Day | Geometric Coefficient of Variation 34.41 |
| Luspatercept 0.6 mg/kg | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.07 1/Day | Geometric Coefficient of Variation 21.48 |
| Luspatercept 0.8 mg/kg | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.06 1/Day | Geometric Coefficient of Variation 19.94 |
| Luspatercept 1.0 mg/kg | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.07 1/Day | Geometric Coefficient of Variation 25.73 |
| Luspatercept 1.25 mg/kg | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.07 1/Day | Geometric Coefficient of Variation 13.34 |
| Expansion Cohort | Apparent Terminal Rate Constant (Lambda z) of Luspatercept | 0.06 1/Day | Geometric Coefficient of Variation 24.19 |
Secondary
Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21)
Blood samples were collected at specified intervals for the determination of AUC0-21. AUC0-21 was defined as the area under the concentration time curve of luspatercept from time zero to Day 21. AUC0-21 was based on non-compartmental analysis and calculated by the linear trapezoidal method.
Time frame: Cycle 1: Days 1, 8, 11, and 15; Day 22 (Cycle 2 Day 1). Cycles 1 and 2 are 21-day cycles
Population: The analysis population consisted of all participants who received ≥1 dose of luspatercept and who had available data for the analysis of AUC0-21.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 11.68 day●µg/mL | Geometric Coefficient of Variation 20.53 |
| Luspatercept 0.4 mg/kg | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 20.66 day●µg/mL | Geometric Coefficient of Variation 22.79 |
| Luspatercept 0.6 mg/kg | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 31.43 day●µg/mL | Geometric Coefficient of Variation 12.16 |
| Luspatercept 0.8 mg/kg | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 54.30 day●µg/mL | Geometric Coefficient of Variation 26.66 |
| Luspatercept 1.0 mg/kg | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 70.39 day●µg/mL | Geometric Coefficient of Variation 34.84 |
| Luspatercept 1.25 mg/kg | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 93.79 day●µg/mL | Geometric Coefficient of Variation 23.75 |
| Expansion Cohort | Area Under the Concentration Time Curve of Luspatercept From Time Zero to Day 21 (AUC0-21) | 62.70 day●µg/mL | Geometric Coefficient of Variation 29.58 |
Secondary
Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC <3 mg/g Dry Weight
Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for NTD participants with baseline LIC \<3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The change from baseline to Day 113 in mean LIC for NTD participants with baseline LIC \<3 mg/g dry weight is presented.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All NTD participants with baseline LIC \<3 mg/g dry weight, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC <3 mg/g Dry Weight | -0.1 mg/g dry weight | Standard Deviation 0.09 |
| Luspatercept 0.4 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC <3 mg/g Dry Weight | -0.5 mg/g dry weight | — |
| Luspatercept 0.6 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC <3 mg/g Dry Weight | 0.9 mg/g dry weight | — |
| Expansion Cohort | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC <3 mg/g Dry Weight | 0.4 mg/g dry weight | Standard Deviation 0.67 |
Secondary
Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight
Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for NTD participants with baseline LIC ≥3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The change from baseline to Day 113 in mean LIC for NTD participants with baseline LIC ≥3 mg/g dry weight is presented.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All NTD participants with baseline LIC ≥3 mg/g dry weight, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | 0.0 mg/g dry weight | Standard Deviation 0.79 |
| Luspatercept 0.4 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -0.6 mg/g dry weight | Standard Deviation 1.22 |
| Luspatercept 0.6 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -0.6 mg/g dry weight | Standard Deviation 2.35 |
| Luspatercept 0.8 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -1.1 mg/g dry weight | Standard Deviation 0.9 |
| Luspatercept 1.0 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -4.5 mg/g dry weight | Standard Deviation 0.18 |
| Expansion Cohort | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Non-transfusion Dependent (NTD) Participants With Baseline LIC ≥3 mg/g Dry Weight | 0.7 mg/g dry weight | Standard Deviation 0.75 |
Secondary
Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC <3 mg/g Dry Weight
Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for TD participants with baseline LIC \<3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The change from baseline to Day 113 in mean LIC for TD participants with baseline LIC \<3 mg/g dry weight is presented.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All TD participants with baseline LIC \<3 mg/g dry weight, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 1.0 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC <3 mg/g Dry Weight | -0.4 mg/g dry weight | Standard Deviation 0.21 |
| Luspatercept 1.25 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC <3 mg/g Dry Weight | 0.2 mg/g dry weight | Standard Deviation 0.76 |
| Expansion Cohort | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC <3 mg/g Dry Weight | 0.2 mg/g dry weight | Standard Deviation 0.29 |
Secondary
Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight
Blood samples were collected at pre-specified time intervals to determine LIC. The change from baseline in mean LIC for TD participants with baseline LIC ≥3 mg/g dry weight was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The change from baseline to Day 113 in mean LIC for TD participants with baseline LIC ≥3 mg/g dry weight is presented.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All TD participants with baseline LIC ≥3 mg/g dry weight, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.6 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -2.1 mg/g dry weight | — |
| Luspatercept 0.8 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -0.7 mg/g dry weight | Standard Deviation 1.18 |
| Luspatercept 1.0 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -0.2 mg/g dry weight | Standard Deviation 6.31 |
| Luspatercept 1.25 mg/kg | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -0.6 mg/g dry weight | — |
| Expansion Cohort | Change From Baseline to End of Treatment in Liver Iron Concentration (LIC) For Transfusion Dependent (TD) Participants With Baseline LIC ≥3 mg/g Dry Weight | -0.6 mg/g dry weight | Standard Deviation 1.77 |
Secondary
Duration of Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval
Duration of erythroid response was defined as the time from the first rolling 12-week window achieving a hemoglobin increase of ≥1.0 g/dL to the date of the last consecutive rolling 12-week window achieving a hemoglobin increase of ≥1.0 g/dL. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The duration of response for participants achieving a hemoglobin increase ≥1.0 g/dL is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug and had data available for the analyses. As defined in the clinical study report, the participants with response were pooled into low and high dose groups to reduce the variation of the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Duration of Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval | 126.0 Days | — |
| Luspatercept 0.4 mg/kg | Duration of Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval | 118.0 Days | Standard Deviation 11.34 |
Secondary
Duration of Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% During a Rolling 12-week Interval
Duration of erythroid response was defined as the time from the first rolling 12-week window achieving a red blood cell (RBC) transfusion burden reduction of ≥50% compared to pretreatment to the last consecutive rolling 12-week window achieving a RBC transfusion burden reduction of ≥50% compared to pretreatment. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The duration of response for participants achieving a RBC transfusion burden reduction of ≥50% compared to pretreatment is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug) and had data available for the analyses. As defined in the clinical study report, the participants with response were pooled into low and high dose groups to reduce the variation of the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.4 mg/kg | Duration of Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% During a Rolling 12-week Interval | 105.0 Days | Standard Deviation 17.23 |
Secondary
Maximum Concentration (Cmax) of Luspatercept
Blood samples were collected at specified intervals for the determination of Cmax. Cmax was defined as the maximum concentration of luspatercept observed after administration. Cmax was based on non-compartmental analysis.
Time frame: Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Day 1
Population: The analysis population consisted of all participants who received ≥1 dose of luspatercept and who had available data for the analysis of Cmax.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Maximum Concentration (Cmax) of Luspatercept | 0.84 µg/mL | Geometric Coefficient of Variation 19.95 |
| Luspatercept 0.4 mg/kg | Maximum Concentration (Cmax) of Luspatercept | 1.52 µg/mL | Geometric Coefficient of Variation 21.9 |
| Luspatercept 0.6 mg/kg | Maximum Concentration (Cmax) of Luspatercept | 2.47 µg/mL | Geometric Coefficient of Variation 9.51 |
| Luspatercept 0.8 mg/kg | Maximum Concentration (Cmax) of Luspatercept | 4.04 µg/mL | Geometric Coefficient of Variation 27.45 |
| Luspatercept 1.0 mg/kg | Maximum Concentration (Cmax) of Luspatercept | 5.73 µg/mL | Geometric Coefficient of Variation 29.85 |
| Luspatercept 1.25 mg/kg | Maximum Concentration (Cmax) of Luspatercept | 6.85 µg/mL | Geometric Coefficient of Variation 21.39 |
| Expansion Cohort | Maximum Concentration (Cmax) of Luspatercept | 4.78 µg/mL | Geometric Coefficient of Variation 23.6 |
Secondary
Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who discontinued study treatment due to an AE is presented.
Time frame: Up to approximately 12 weeks
Population: All participants who received ≥1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 0 Participants |
| Luspatercept 0.4 mg/kg | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 0 Participants |
| Luspatercept 0.6 mg/kg | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 1 Participants |
| Luspatercept 0.8 mg/kg | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 2 Participants |
| Luspatercept 1.0 mg/kg | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 0 Participants |
| Luspatercept 1.25 mg/kg | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 0 Participants |
| Expansion Cohort | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) | 2 Participants |
Secondary
Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)
DLTs were determined using the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) and graded as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences; and Grade 5=death related to AE. The occurrence of any of the following toxicities occurring up to 28 days after the first dose was considered a DLT: treatment-related serious adverse event (SAE) ≥ Grade 3; treatment related non-hematologic adverse event (AE) ≥ Grade 3; and treatment related hematologic AE ≥ Grade 4. The number of participants who experienced a DLT is presented.
Time frame: Up to 28 days
Population: The DLT analysis population consisted of all participants who received ≥1 dose of study treatment and were observed for DLTs for 28 days after the first dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Luspatercept 0.4 mg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Luspatercept 0.6 mg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Luspatercept 0.8 mg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
| Luspatercept 1.0 mg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Luspatercept 1.25 mg/kg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Expansion Cohort | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experienced an AE is presented.
Time frame: Up to approximately 20 weeks
Population: All participants who received ≥1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Luspatercept 0.4 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| Luspatercept 0.6 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Luspatercept 0.8 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| Luspatercept 1.0 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| Luspatercept 1.25 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) | 5 Participants |
| Expansion Cohort | Number of Participants Who Experienced an Adverse Event (AE) | 26 Participants |
Secondary
Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater
AEs were graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) and graded as follows: Grade 1=mild; Grade 2=moderate; Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening consequences; and Grade 5=death related to AE. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experienced an AE of ≥Grade 3 is presented.
Time frame: Up to approximately 20 weeks
Population: All participants who received ≥1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 0 Participants |
| Luspatercept 0.4 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 1 Participants |
| Luspatercept 0.6 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 0 Participants |
| Luspatercept 0.8 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 1 Participants |
| Luspatercept 1.0 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 2 Participants |
| Luspatercept 1.25 mg/kg | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 0 Participants |
| Expansion Cohort | Number of Participants Who Experienced an Adverse Event (AE) of Grade 3 or Greater | 4 Participants |
Secondary
Number of Participants Who Experienced a Serious Adverse Event (SAE)
An SAE was any adverse event, occurring at any dose level/regimen and regardless of causality that: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or was an important medical event. The number of participants who experienced an SAE is presented.
Time frame: Up to approximately 20 weeks
Population: All participants who received ≥1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 0 Participants |
| Luspatercept 0.4 mg/kg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 1 Participants |
| Luspatercept 0.6 mg/kg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 0 Participants |
| Luspatercept 0.8 mg/kg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 0 Participants |
| Luspatercept 1.0 mg/kg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 0 Participants |
| Luspatercept 1.25 mg/kg | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 0 Participants |
| Expansion Cohort | Number of Participants Who Experienced a Serious Adverse Event (SAE) | 0 Participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval
A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.0 g/dL from baseline during a 12-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. A 12-week interval was defined as any consecutive 12 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.0 g/dL from baseline is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 Weeks)
Population: All participants who received ≥1 dose of study treatment and received \<4 units of RBCs within 8 weeks prior to the first dose of study drug and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 16.7 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 80.0 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 66.7 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 12-week Interval | 60.0 Percentage of participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval
A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.0 g/dL from baseline during an 8-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. An 8-week interval was defined as any consecutive 8 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.0 g/dL from baseline is presented.
Time frame: Any 8-week interval during the study (up to approximately 20 Weeks)
Population: All participants who received ≥1 dose of study treatment and received \<4 units of RBCs within 8 weeks prior to the first dose of study drug and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 16.7 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 16.7 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 80.0 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 66.7 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.0 g/dL From Baseline During a Rolling 8-week Interval | 70.0 Percentage of participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval
A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline during a 12-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. A 12-week interval was defined as any consecutive 12 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 Weeks)
Population: All participants who received ≥1 dose of study treatment and received \<4 units of RBCs within 8 weeks prior to the first dose of study drug and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 33.3 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 12-week Interval | 50.0 Percentage of participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval
A modified erythroid response in NTD participants was defined as a mean hemoglobin increase of ≥1.5 g/dL from baseline during an 8-week interval compared to baseline. Baseline hemoglobin for NTD participants was the average of two or more measurements performed during the screening period. Hemoglobin measurements within 2 weeks following red blood cell (RBC) transfusion or 56 days after the last dose were excluded from analysis. NTD participants were participants who had received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug. An 8-week interval was defined as any consecutive 8 weeks during the study. The percentage of participants with a hemoglobin increase of ≥1.5 g/dL from baseline is presented.
Time frame: Any 8-week interval during the study (up to approximately 20 Weeks)
Population: All participants who received ≥1 dose of study treatment and received \<4 units of RBCs within 8 weeks prior to the first dose of study drug and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 0.0 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 33.3 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With a Hemoglobin Increase of ≥1.5 g/dL From Baseline During a Rolling 8-week Interval | 60.0 Percentage of participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment
LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in NTD participants with a baseline LIC of ≥3 mg/g dry weight. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of NTD participants with baseline LIC ≥3 mg/g dry weight who have demonstrated an LIC response is presented.
Time frame: End of Treatment (up to Day 113)
Population: All NTD participants with baseline LIC ≥3 mg/g dry weight, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 25.0 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 60.0 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 100 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment
LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in NTD participants with a baseline LIC of ≥3 mg/g dry weight and who have not used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of NTD participants with baseline LIC ≥3 mg/g dry weight, who have not used ICT, and who have demonstrated an LIC response is presented.
Time frame: End of Treatment (up to Day 113)
Population: All NTD participants with baseline LIC ≥3 mg/g dry weight, who have not used ICT, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 33.3 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
Secondary
Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment
LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in NTD participants with a baseline LIC of ≥3 mg/g dry weight and who have used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. NTD participants were participants who had received \<4 units of RBCs within 8 weeks prior to the first dose of study drug. The percentage of NTD participants with baseline LIC ≥3 mg/g dry weight, who have used ICT, and who have demonstrated an LIC response is presented.
Time frame: End of Treatment (up to Day 113)
Population: All NTD participants with baseline LIC ≥3 mg/g dry weight, who have used ICT, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
| Luspatercept 0.4 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 100 Percentage of participants |
| Luspatercept 0.6 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 100 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 100 Percentage of participants |
| Expansion Cohort | Percentage of Non-transfusion Dependent (NTD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
Secondary
Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks
Transfusion independence for TD participants was defined as the percentage of participants who did not require RBC transfusion units (or milliliters) transfused for ≥8 weeks in the study after start of treatment. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of participants who maintained transfusion independence for ≥8 weeks is presented.
Time frame: Any 8-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug) and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.6 mg/kg | Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks | 100 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks | 0.0 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks | 75.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants Who Maintained Red Blood Cell (RBC) Transfusion Independence For ≥8 Weeks | 10.5 Percentage of participants |
Secondary
Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval
Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during a 12-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 12 weeks prior to the start of treatment (baseline). TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). A 12-week interval was defined as any consecutive 12 weeks during the study. The percentage of participants with a ≥50% reduction in RBC transfusion burden from baseline is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug) and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.6 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 100 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 66.7 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 100 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 50.0 Percentage of participants |
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 12-week Interval | 42.1 Percentage of participants |
Secondary
Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval
Transfusion burden for TD participants was defined as the ratio of RBC transfusion units (or milliliters) transfused during an 8-week interval divided by the duration of that interval compared to the ratio of RBC transfusion units 8 weeks prior to the start of treatment (baseline). TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). An 8-week interval was defined as any consecutive 8 weeks during the study. The percentage of participants with a ≥50% reduction in RBC transfusion burden from baseline is presented.
Time frame: Any 8-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug) and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.6 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval | 100 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval | 100 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval | 100 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval | 75.0 Percentage of participants |
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants With a ≥50% Reduction in Red Blood Cell (RBC) Transfusion Burden From Baseline During a Rolling 8-week Interval | 78.9 Percentage of participants |
Secondary
Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment
LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in TD participants with a baseline LIC of ≥3 mg/g dry weight. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of TD participants with baseline LIC ≥3 mg/g dry weight who have demonstrated an LIC response is presented.
Time frame: End of Treatment (up to Day 113)
Population: All TD participants with baseline LIC ≥3 mg/g dry weight, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.6 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 100 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 33.3 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight Who Have Demonstrated an LIC Response at End of Treatment | 33.3 Percentage of participants |
Secondary
Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment
LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in TD participants with a baseline LIC of ≥3 mg/g dry weight and who have not used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of TD participants with baseline LIC ≥3 mg/g dry weight, who have not used ICT, and who have demonstrated an LIC response is presented.
Time frame: End of Treatment (up to Day 113)
Population: All TD participants with baseline LIC ≥3 mg/g dry weight, who have not used ICT, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Not Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
Secondary
Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment
LIC response was defined as a demonstrated LIC reduction of ≥1 mg/g dry weight. Blood samples were collected at pre-specified time intervals to determine LIC in TD participants with a baseline LIC of ≥3 mg/g dry weight and who have used ICT. LIC was measured using magnetic resonance imaging (MRI). Baseline was the last measurement prior to the first dose of study drug. TD participants were participants who had received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug). The percentage of TD participants with baseline LIC ≥3 mg/g dry weight, who have used ICT, and who have demonstrated an LIC response is presented.
Time frame: End of Treatment (up to Day 113)
Population: All TD participants with baseline LIC ≥3 mg/g dry weight, who have used ICT, who received ≥1 dose of study treatment, and had data available for the analyses
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Luspatercept 0.6 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 100 Percentage of participants |
| Luspatercept 0.8 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 33.3 Percentage of participants |
| Luspatercept 1.0 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 50.0 Percentage of participants |
| Luspatercept 1.25 mg/kg | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 0.0 Percentage of participants |
| Expansion Cohort | Percentage of Transfusion Dependent (TD) Participants With Baseline Liver Iron Concentration (LIC) of ≥3 mg/g Dry Weight, Who Have Used Iron Chelation Therapy (ICT), and Who Have Demonstrated an LIC Response at End of Treatment | 40.0 Percentage of participants |
Secondary
Percent Change From Baseline to Day 113 in Calculated Transferrin Saturation
The calculated transferrin saturation is the ratio of the serum iron concentration and the total iron binding capacity (TIBC) expressed as a percentage. Blood samples were to be collected at pre-specified time intervals for serum iron and TIBC to determine the calculated transferrin saturation. Baseline was pre-specified to be the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and Day 113
Population: No data were collected for Percent Change From Baseline to Day 113 in Calculated Transferrin Saturation.
Secondary
Percent Change From Baseline to Day 113 in Serum Non-transferrin Bound Iron (NTBI)
Blood samples were to be collected at pre-specified time intervals to determine NTBI. Baseline was pre-specified to be the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and Day 113
Population: No data were collected for Percent Change From Baseline to Day 113 in Serum NTBI.
Secondary
Percent Change From Baseline to End of Treatment in Alpha Globin Gene
Blood samples were collected at pre-specified time intervals to determine alpha globin gene. The percent change from baseline in alpha globin gene was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for alpha globin gene analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | 42.27 Percent change | Standard Deviation 47.176 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | -49.73 Percent change | Standard Deviation 27.324 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | -7.11 Percent change | Standard Deviation 79.335 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | 389.87 Percent change | Standard Deviation 865.827 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | 396.72 Percent change | Standard Deviation 329.535 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | -10.85 Percent change | Standard Deviation 54.653 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Alpha Globin Gene | 1124.14 Percent change | Standard Deviation 2032.635 |
Secondary
Percent Change From Baseline to End of Treatment in Beta Globin Gene
Blood samples were collected at pre-specified time intervals to determine beta globin gene. The percent change from baseline in beta globin gene was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for beta globin gene analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Beta Globin Gene | 36.29 Percent change | Standard Deviation 41.033 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Beta Globin Gene | -49.17 Percent change | Standard Deviation 29.282 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Beta Globin Gene | -15.50 Percent change | Standard Deviation 48.554 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Beta Globin Gene | 51.75 Percent change | Standard Deviation 85.913 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Beta Globin Gene | 276.26 Percent change | Standard Deviation 215.713 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Beta Globin Gene | -6.51 Percent change | Standard Deviation 109.753 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Beta Globin Gene | 1056.22 Percent change | Standard Deviation 2400.719 |
Secondary
Percent Change From Baseline to End of Treatment in Erythropoietin
Blood samples were collected at pre-specified time intervals to determine erythropoietin. The percent change from baseline in erythropoietin was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for erythropoietin analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Erythropoietin | -11.18 Percent change | Standard Deviation 55.236 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Erythropoietin | 10.44 Percent change | Standard Deviation 42.542 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Erythropoietin | 88.57 Percent change | Standard Deviation 235.111 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Erythropoietin | 210.69 Percent change | Standard Deviation 311.768 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Erythropoietin | 97.54 Percent change | Standard Deviation 141.98 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Erythropoietin | 183.79 Percent change | Standard Deviation 189.662 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Erythropoietin | 116.25 Percent change | Standard Deviation 245.118 |
Secondary
Percent Change From Baseline to End of Treatment in Ferritin
Blood samples were collected at pre-specified time intervals to determine ferritin. The percent change from baseline in ferritin was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for ferritin analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Ferritin | -18.5 Percent change | Standard Deviation 17.8 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Ferritin | 8.4 Percent change | Standard Deviation 27.2 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Ferritin | -4.5 Percent change | Standard Deviation 14.9 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Ferritin | -23.7 Percent change | Standard Deviation 27.8 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Ferritin | -23.2 Percent change | Standard Deviation 19.4 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Ferritin | -25.2 Percent change | Standard Deviation 22.7 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Ferritin | -23.7 Percent change | Standard Deviation 24.7 |
Secondary
Percent Change From Baseline to End of Treatment in Gamma Globin Gene
Blood samples were collected at pre-specified time intervals to determine gamma globin gene. The percent change from baseline in gamma globin gene was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for gamma globin gene analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | 81.70 Percent change | Standard Deviation 97.1 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | -44.57 Percent change | Standard Deviation 54.656 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | -3.32 Percent change | Standard Deviation 109.612 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | 468.05 Percent change | Standard Deviation 967.579 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | 229.46 Percent change | Standard Deviation 118.097 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | -45.40 Percent change | Standard Deviation 32.267 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Gamma Globin Gene | 1054.42 Percent change | Standard Deviation 1869.511 |
Secondary
Percent Change From Baseline to End of Treatment in Haptoglobin
Blood samples were collected at pre-specified time intervals to determine haptoglobin. The percent change from baseline in haptoglobin was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for haptoglobin analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Haptoglobin | 21.8 Percent change | Standard Deviation 147.4 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Haptoglobin | 281.0 Percent change | Standard Deviation 434.8 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Haptoglobin | -16.2 Percent change | Standard Deviation 51.8 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Haptoglobin | -31.2 Percent change | Standard Deviation 24.9 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Haptoglobin | 30.3 Percent change | Standard Deviation 181.8 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Haptoglobin | -55.1 Percent change | Standard Deviation 28.8 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Haptoglobin | -32.3 Percent change | Standard Deviation 44.3 |
Secondary
Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2)
Blood samples were collected at pre-specified time intervals to determine Hb A2. The percent change from baseline in Hb A2 was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for Hb A2 analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | 1.14 Percent change | Standard Deviation 21.859 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | -14.97 Percent change | Standard Deviation 50.202 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | 6.72 Percent change | Standard Deviation 28.515 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | -11.49 Percent change | Standard Deviation 50.714 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | 26.34 Percent change | Standard Deviation 33.776 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | 38.04 Percent change | Standard Deviation 52.758 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hemoglobin A2 (Hb A2) | 6.15 Percent change | Standard Deviation 18.011 |
Secondary
Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A)
Blood samples were collected at pre-specified time intervals to determine Hb A. The percent change from baseline in Hb A was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for Hb A analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | -1.96 Percent change | Standard Deviation 7.207 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | 308.31 Percent change | Standard Deviation 621.15 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | -5.41 Percent change | Standard Deviation 28.623 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | -5.00 Percent change | Standard Deviation 16.058 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | -22.70 Percent change | Standard Deviation 35 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | -32.91 Percent change | Standard Deviation 45.256 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hemoglobin A (Hb A) | -8.46 Percent change | Standard Deviation 20.11 |
Secondary
Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C)
Blood samples were collected at pre-specified time intervals to determine Hb C. The percent change from baseline in Hb C was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for Hb C analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hemoglobin C (Hb C) | 0.00 Percent change | Standard Deviation 0 |
Secondary
Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D)
Blood samples were collected at pre-specified time intervals to determine Hb D. The percent change from baseline in Hb D was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for Hb D analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hemoglobin D (Hb D) | 0.00 Percent change | Standard Deviation 0 |
Secondary
Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F)
Blood samples were collected at pre-specified time intervals to determine Hb F. The percent change from baseline in Hb F was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for Hb F analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | 14.45 Percent change | Standard Deviation 7.734 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | -1.96 Percent change | Standard Deviation 13.245 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | 37.52 Percent change | Standard Deviation 98.772 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | 20.94 Percent change | Standard Deviation 40.153 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | 70.89 Percent change | Standard Deviation 57.386 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | 308.66 Percent change | Standard Deviation 295.486 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hemoglobin F (Hb F) | 77.85 Percent change | Standard Deviation 91.56 |
Secondary
Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S)
Blood samples were collected at pre-specified time intervals to determine Hb S. The percent change from baseline in Hb S was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for Hb S analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hemoglobin S (Hb S) | 0.00 Percent change | Standard Deviation 0 |
Secondary
Percent Change From Baseline to End of Treatment in Hepcidin
Blood samples were collected at pre-specified time intervals to determine hepcidin. The percent change from baseline in hepcidin was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for hepcidin analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Hepcidin | 7.5 Percent change | Standard Deviation 41.1 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Hepcidin | 58.4 Percent change | Standard Deviation 141 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Hepcidin | -4.8 Percent change | Standard Deviation 27.8 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Hepcidin | 0.7 Percent change | Standard Deviation 83.3 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Hepcidin | -41.2 Percent change | Standard Deviation 12.7 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Hepcidin | -13.6 Percent change | — |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Hepcidin | -22.0 Percent change | Standard Deviation 20.9 |
Secondary
Percent Change From Baseline to End of Treatment in Indirect Bilirubin
Blood samples were collected at pre-specified time intervals to determine indirect bilirubin. The percent change from baseline in indirect bilirubin was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for indirect bilirubin analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | 13.9 Percent change | Standard Deviation 23.7 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | -25.2 Percent change | Standard Deviation 18.3 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | 4.8 Percent change | Standard Deviation 8.7 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | 6.3 Percent change | Standard Deviation 20.3 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | 3.7 Percent change | Standard Deviation 21.4 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | 2.8 Percent change | Standard Deviation 53.6 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Indirect Bilirubin | 18.3 Percent change | Standard Deviation 38.7 |
Secondary
Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH)
Blood samples were collected at pre-specified time intervals to determine LDH. The percent change from baseline in LDH was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for LDH analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | 0.4 Percent change | Standard Deviation 17.5 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | -0.9 Percent change | Standard Deviation 10.5 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | 8.7 Percent change | Standard Deviation 25.1 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | 29.2 Percent change | Standard Deviation 25.2 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | 37.4 Percent change | Standard Deviation 64.5 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | 53.8 Percent change | Standard Deviation 68.2 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Lactate Dehydrogenase (LDH) | 45.0 Percent change | Standard Deviation 68.5 |
Secondary
Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP)
Blood samples were collected at pre-specified time intervals to determine BSAP. The percent change from baseline in BSAP was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for BSAP analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | 42.6 Percent change | Standard Deviation 14.5 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | 3.4 Percent change | Standard Deviation 53 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | 8.4 Percent change | Standard Deviation 31.3 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | 23.6 Percent change | Standard Deviation 33.3 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | 12.7 Percent change | Standard Deviation 53.3 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | -20.9 Percent change | Standard Deviation 31.9 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Mean Bone-specific Alkaline Phosphatase (BSAP) | 22.2 Percent change | Standard Deviation 57.7 |
Secondary
Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX)
Blood samples were collected at pre-specified time intervals to determine CTX. The percent change from baseline in CTX was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for CTX analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | -35.1 Percent change | Standard Deviation 10.9 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | 15.5 Percent change | Standard Deviation 56.2 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | 17.7 Percent change | Standard Deviation 9.3 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | 20.1 Percent change | Standard Deviation 20.8 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | 0.7 Percent change | Standard Deviation 10.2 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | -0.2 Percent change | Standard Deviation 17.2 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Mean C-telopeptide of Type I Collagen (CTX) | 22 Percent change | Standard Deviation 38.1 |
Secondary
Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count
Blood samples were collected at pre-specified time intervals to determine nRBC count. The percent change from baseline in nRBC count was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for nRBC count analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | -70.19 Percent change | Standard Deviation 42.019 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | 17.20 Percent change | Standard Deviation 79.244 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | 211.82 Percent change | Standard Deviation 158.143 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | 163.63 Percent change | Standard Deviation 178.379 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | 176.62 Percent change | Standard Deviation 209.327 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | 385.71 Percent change | Standard Deviation 121.218 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Nucleated Red Blood Cell (nRBC) Count | 1062.20 Percent change | Standard Deviation 1890.881 |
Secondary
Percent Change From Baseline to End of Treatment in Reticulocytes
Blood samples were collected at pre-specified time intervals to determine reticulocytes. The percent change from baseline in reticulocytes was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for reticulocyte analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Reticulocytes | -12.41 Percent change | Standard Deviation 19.386 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Reticulocytes | -2.03 Percent change | Standard Deviation 26.173 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Reticulocytes | -9.91 Percent change | Standard Deviation 54.978 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Reticulocytes | 73.38 Percent change | Standard Deviation 61.328 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Reticulocytes | 25.35 Percent change | Standard Deviation 95.741 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Reticulocytes | 136.03 Percent change | Standard Deviation 112.261 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Reticulocytes | 151.26 Percent change | Standard Deviation 435.508 |
Secondary
Percent Change From Baseline to End of Treatment in Serum Iron
Blood samples were collected at pre-specified time intervals to determine serum iron. The percent change from baseline in serum iron was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for serum iron analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Serum Iron | -15.8 Percent change | Standard Deviation 26.9 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Serum Iron | -9.0 Percent change | Standard Deviation 38 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Serum Iron | 7.8 Percent change | Standard Deviation 15.1 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Serum Iron | -12.9 Percent change | Standard Deviation 31.5 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Serum Iron | -5.4 Percent change | Standard Deviation 35.8 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Serum Iron | -12.4 Percent change | Standard Deviation 18.4 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Serum Iron | 2.1 Percent change | Standard Deviation 38.2 |
Secondary
Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor
Blood samples were collected at pre-specified time intervals to determine soluble transferrin receptor. The percent change from baseline in soluble transferrin receptor was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for soluble transferrin receptor analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | 3.6 Percent change | Standard Deviation 10.9 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | -5.9 Percent change | Standard Deviation 5.2 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | 10.6 Percent change | Standard Deviation 34.5 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | 36.3 Percent change | Standard Deviation 41.3 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | 68.2 Percent change | Standard Deviation 60.4 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | 83.3 Percent change | Standard Deviation 90.4 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Soluble Transferrin Receptor | 49.2 Percent change | Standard Deviation 56.9 |
Secondary
Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC)
Blood samples were collected at pre-specified time intervals to determine TIBC. The percent change from baseline in TIBC was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for TIBC analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | 2.9 Percent change | Standard Deviation 7 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | -1.5 Percent change | Standard Deviation 7.4 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | 3.5 Percent change | Standard Deviation 7.8 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | -4.9 Percent change | Standard Deviation 11.7 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | -2.1 Percent change | Standard Deviation 6.2 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | -0.8 Percent change | Standard Deviation 4.3 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Total Iron Binding Capacity (TIBC) | 1.3 Percent change | Standard Deviation 12.1 |
Secondary
Percent Change From Baseline to End of Treatment in Transferrin
Blood samples were collected at pre-specified time intervals to determine transferrin. The percent change from baseline in transferrin was measured. Baseline was the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of study drug) and End of Treatment (up to Day 113)
Population: All participants who received ≥1 dose of study treatment and had data available for transferrin analyses
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Percent Change From Baseline to End of Treatment in Transferrin | 4.0 Percent change | Standard Deviation 6.7 |
| Luspatercept 0.4 mg/kg | Percent Change From Baseline to End of Treatment in Transferrin | -1.5 Percent change | Standard Deviation 6 |
| Luspatercept 0.6 mg/kg | Percent Change From Baseline to End of Treatment in Transferrin | 3.0 Percent change | Standard Deviation 8.5 |
| Luspatercept 0.8 mg/kg | Percent Change From Baseline to End of Treatment in Transferrin | -4.7 Percent change | Standard Deviation 11.3 |
| Luspatercept 1.0 mg/kg | Percent Change From Baseline to End of Treatment in Transferrin | -1.0 Percent change | Standard Deviation 7.5 |
| Luspatercept 1.25 mg/kg | Percent Change From Baseline to End of Treatment in Transferrin | -1.6 Percent change | Standard Deviation 5.6 |
| Expansion Cohort | Percent Change From Baseline to End of Treatment in Transferrin | 1.0 Percent change | Standard Deviation 11.5 |
Secondary
Terminal Elimination Half Life (t½) of Luspatercept
Blood samples were collected at specified intervals for the determination of t½. t½ was defined as the time required to divide the serum concentration of luspatercept by two after reaching pseudo-equilibrium. t½ was based on non-compartmental analysis.
Time frame: Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Days 1 and 8; Cycles 4 and 5 (21-day cycles): Days 1, 8, and 15; study follow-up on Days 113, 141, and 169
Population: The analysis population consisted of all participants who received ≥1 dose of luspatercept and who had available data for the analysis of t½.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Terminal Elimination Half Life (t½) of Luspatercept | 11.56 Days | Geometric Coefficient of Variation 27.52 |
| Luspatercept 0.4 mg/kg | Terminal Elimination Half Life (t½) of Luspatercept | 10.12 Days | Geometric Coefficient of Variation 34.41 |
| Luspatercept 0.6 mg/kg | Terminal Elimination Half Life (t½) of Luspatercept | 9.65 Days | Geometric Coefficient of Variation 21.48 |
| Luspatercept 0.8 mg/kg | Terminal Elimination Half Life (t½) of Luspatercept | 11.22 Days | Geometric Coefficient of Variation 19.94 |
| Luspatercept 1.0 mg/kg | Terminal Elimination Half Life (t½) of Luspatercept | 9.42 Days | Geometric Coefficient of Variation 25.73 |
| Luspatercept 1.25 mg/kg | Terminal Elimination Half Life (t½) of Luspatercept | 10.37 Days | Geometric Coefficient of Variation 13.34 |
| Expansion Cohort | Terminal Elimination Half Life (t½) of Luspatercept | 10.79 Days | Geometric Coefficient of Variation 24.19 |
Secondary
Time To Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval by Pooled Dose Groups
Time to erythroid response was defined as the time from first dose to the first date of any rolling 12-week window achieving a hemoglobin increase ≥1.0 g/dL. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The time to the first date of any rolling 12-week window achieving a hemoglobin increase ≥1.0 g/dL is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and received \<4 units of red blood cells (RBCs) within 8 weeks prior to the first dose of study drug and had data available for the analyses. As defined in the clinical study report, the participants with response were pooled into low and high dose groups to reduce the variation of the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.2 mg/kg | Time To Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval by Pooled Dose Groups | 8.0 Days | — |
| Luspatercept 0.4 mg/kg | Time To Erythroid Response for Non-transfusion Dependent (NTD) Participants Who Achieved a Hemoglobin Increase ≥1.0 g/dL During a Rolling 12-week Interval by Pooled Dose Groups | 9.9 Days | Standard Deviation 6.29 |
Secondary
Time To Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% During a Rolling 12-week Interval
Time to erythroid response was defined as the time from the first dose to the first date of any rolling 12-week window achieving a red blood cell (RBC) transfusion burden reduction of ≥50% compared to pretreatment. When there were multiple disjointed intervals with response, the longest interval was used. Participants with response ongoing by analysis cutoff were censored. The time to the first date of any rolling 12-week window achieving a red blood cell transfusion burden reduction of ≥50% compared to pretreatment is presented.
Time frame: Any 12-week interval during the study (up to approximately 20 weeks)
Population: All participants who received ≥1 dose of study treatment and have received ≥4 units of RBCs every 8 weeks (confirmed over 6 months prior to the first dose of study drug) and had data available for the analyses. As defined in the clinical study report, the participants with response were pooled into low and high dose groups to reduce the variation of the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Luspatercept 0.4 mg/kg | Time To Erythroid Response for Transfusion Dependent (TD) Participants Who Achieved a Transfusion Burden Reduction of ≥50% During a Rolling 12-week Interval | 4.8 Days | Standard Deviation 8.3 |
Secondary
Time to Maximum Concentration (Tmax) of Luspatercept
Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as the time to maximum concentration of luspatercept observed after administration. Tmax was based on non-compartmental analysis.
Time frame: Cycle 1 (21-day cycle): Days 1, 8, 11, and 15; Cycle 2 (21-day cycle): Day 1
Population: The analysis population consisted of all participants who received ≥1 dose of luspatercept and who had available data for the analysis of Tmax.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Luspatercept 0.2 mg/kg | Time to Maximum Concentration (Tmax) of Luspatercept | 7.00 Days |
| Luspatercept 0.4 mg/kg | Time to Maximum Concentration (Tmax) of Luspatercept | 7.00 Days |
| Luspatercept 0.6 mg/kg | Time to Maximum Concentration (Tmax) of Luspatercept | 7.50 Days |
| Luspatercept 0.8 mg/kg | Time to Maximum Concentration (Tmax) of Luspatercept | 7.00 Days |
| Luspatercept 1.0 mg/kg | Time to Maximum Concentration (Tmax) of Luspatercept | 7.00 Days |
| Luspatercept 1.25 mg/kg | Time to Maximum Concentration (Tmax) of Luspatercept | 7.00 Days |
| Expansion Cohort | Time to Maximum Concentration (Tmax) of Luspatercept | 7.00 Days |