CompletedNCT01749514Updated Jul 29, 2024Results posted

Study of Luspatercept for the Treatment of Anemia in Patients With Myelodysplastic Syndrome (MDS) (MK-6143-001)

A Phase 2 interventional study of Luspatercept in Anemia, sponsored by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA. Completed at 1 site in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-29.

Sponsored by Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 116
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

The purpose of this study is to evaluate the effects of luspatercept (MK-6143, formerly called ACE-536) on anemia in patients with low or intermediate-1 risk myelodysplastic syndrome (MDS). There is no primary hypothesis in this study.

Conditions studied

Anemia

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Keywords

Myelodysplastic Syndrome

In context

Preleukemia

1,317 studies on the registry are indexed under Preleukemia; 57 are open to participants now.

This study's enrollment of 116 is above the median of 36 across 1,060 interventional studies indexed under Preleukemia.

Browse Preleukemia studies →

Lead sponsor

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA is the lead sponsor of 25 studies on the registry; none are open to participants now.

Of its 8 completed or terminated interventional studies of FDA-regulated products, 7 (88%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Key Inclusion Criteria:

Documented diagnosis of idiopathic/de novo myelodysplastic syndrome (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML), according to WHO criteria (white blood count, 13,000/uL), that meets International Prognostic Scoring System (IPSS) classification of low or intermediate-1 risk disease as determined by microscopic and standard cytogenetic analyses of the bone marrow and peripheral complete blood count (CBC) obtained during screening
Anemia defined as:
- 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 7-28 days prior to Cycle 1 Day 1, not influenced by red blood cell (RBC) transfusion within 7 days of measurement for non-transfusion dependent patients (defined as having received \<4 units of RBCs within 8 weeks prior to Cycle 1 Day 1), or Transfusion dependent, defined as having received ≥4 units of RBCs within 8 weeks prior to Cycle 1 Day 1
Serum erythropoietin levels and prior erythropoiesis-stimulating agent (ESA) treatment:
Dose escalation cohorts and expansion cohort 1 patients: Serum erythropoietin level >500 U/L, OR, if ≤500 U/L, patient is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents (ESAs), or ESAs are contraindicated or unavailable
Expansion cohort 2 patients: If patient is RS+ (defined as having ≥15% ring sideroblasts in the bone marrow), no prior ESA treatment and serum erythropoietin level ≤ 200 U/L. If a patient is RS- (defined as having \<15% ring sideroblasts in the bone marrow), prior ESA treatment and any serum erythropoietin level is allowed
No alternative treatment options, per applicable MDS guidelines, are available and/or appropriate for the patient, at the discretion of the investigator
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia).
Adequate renal (creatinine ≤2 x upper limit of normal [ULN]) and hepatic (total bilirubin \<2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<3 x ULN) function
Adequate transferrin saturation (≥15%), ferritin (≥ 50 µg/L), folate (≥4.5 nmol/L [≥2.0 µg/L]) and vitamin B12 (≥148 pmol/L [≥ 200 pg/mL]) during screening (supplementation and retest during screening is acceptable)
Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of luspatercept. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential while participating in the study and for 12 weeks following the last dose of luspatercept, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of luspatercept
Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements
Patients understand and are able to provide written informed consent

Key Exclusion Criteria:

Prior treatment with azacitidine or decitabine
Treatment within 28 days prior to Cycle 1 Day 1 with:
- Erythropoiesis stimulating agent (ESA)
- Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)
- Lenalidomide
Iron chelation therapy if initiated within 56 days prior to 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 product is known, within 5 times the half-life prior to Cycle 1 Day 1, whichever is longer
Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1
Platelet count \<30 x 109/L.
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
History of stroke, deep venous thrombosis (DVT) or arterial embolism within 6 months prior to Cycle 1 Day 1
Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
Any malignancy other than MDS which has not been in remission and/or has required systemic therapy including radiation, chemotherapy, hormonal therapy or surgery, within the last year prior to Cycle 1 Day 1
Uncontrolled hypertension, defined as systolic blood pressure (BP) ≥ 150 mm Hg or diastolic BP ≥ 100 mm Hg
Pregnant or lactating females
History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug
Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study
Transfusion event within 7 days prior to Cycle 1 Day 1
Prior treatment with sotatercept (MK-7962, formerly called ACE-011) or luspatercept.
Secondary MDS

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 116 participants (actual)

Study arms

Experimental
Luspatercept 0.125mg/kg (Cohort 1)
Participants receive luspatercept 0.125mg/kg as a subcutaneous (SC) injection every 3 weeks (Q3W) on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Luspatercept 0.25mg/kg (Cohort 2)
Participants receive luspatercept titrated up to 0.25mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Luspatercept 0.50mg/kg (Cohort 3)
Participants receive luspatercept titrated up to 0.50mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Luspatercept 0.75mg/kg (Cohort 4)
Participants receive luspatercept titrated up to 0.75mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Luspatercept 1.00mg/kg (Cohort 5)
Participants receive luspatercept titrated up to 1.00mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Luspatercept 1.33mg/kg (Cohort 6)
Participants receive luspatercept titrated up to 1.33mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Luspatercept 1.75mg/kg (Cohort 7)
Participants receive luspatercept titrated up to 1.75mg/kg via Fibonacci scheme, SC injection Q3W on Day 1 of each cycle for up to 5 cycles (each cycle length = 21 days).
Drug: Luspatercept
Experimental
Expansion Cohort
Participants receive an initial dose of luspatercept 1.0mg/kg SC on Day 1 of the Cycle 1 (Cycle length = 21 days). For each subsequent cycle (up to 5 cycles), the dose was titrated via Fibonacci scheme up to a maximum dose of 1.75mg/kg based on the safety review team (SRT) recommendations
Drug: Luspatercept

Interventions

DrugLuspatercept
Participants receive luspatercept up to 1.75mg/kg subcutaneously (SC) every 3 weeks for up to 5 cycles (each cycle length = 21 days).
Also known as: MK-6143, A536

What researchers measure

Primary outcomes

Percentage of Low Transfusion Burden (LTB) Participants With Modified Erythroid Response (mHI-E)
The mHI-E for LTB participants was defined as a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days or rolling 2 weeks (in the absence of red blood cell \[RBC\] transfusions). Hemoglobin measurements within 7 days following RBC transfusion were excluded from analysis. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Rolling 2 weeks was defined as any consecutive 2 weeks during the study. The percentage of LTB participants with mHI-E were reported.
Time frame: Any consecutive 2 weeks during the study (up to approximately 75 weeks)
Percentage of High Transfusion Burden (HTB) Participants With mHI-E
The mHI-E for HTB participants was defined as a ≥4 units or ≥50% reduction in RBC transfusion burden during any rolling 8-week window compared to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. The percentage of HTB participants with mHI-E were reported.
Time frame: Any consecutive 8 weeks during the study (up to approximately 75 weeks)

Secondary outcomes

Number of Participants Who Experienced an Adverse Event (AE)
An adverse event (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 can 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 were reported.
Time frame: Up to approximately 24 weeks
Number of Participants Who Discontinued Study Treatment Due To an AE
An adverse event (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 can 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 were reported.
Time frame: Up to approximately 12 weeks
Rate of Erythroid Response (HI-E) Per International Working Group (IWG) 2006 Response Criteria
Per IWG 2006 response criteria, rate of HI-E is defined as the percentage of participants for whom the mean of all hemoglobin value from baseline during any rolling 8-week increased ≥1.5 g/dL in the absence of transfusion for LTB participants, or a reduction by ≥4 units of RBCs transfusion over any rolling 8-week window for HTB patients. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study.
Time frame: Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)
Rate of Platelet Response (HI-P) Per IWG 2006 Criteria
Per IWG 2006 response criteria, HI-P was defined for participants with baseline value ≥20 x 10\^9/L as the platelet increase in any rolling 8 weeks ≥30 x 10\^9 and for participants with baseline value \<20 x 10\^9/L as the platelet increase in any rolling 8 weeks \>20 x 10\^9/L with increase of at least 100%. The rolling 8-week was defined as any consecutive 8 weeks during the study. The percentage of participants with HI-P were reported.
Time frame: Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)
Rate of Neutrophil Response (HI-N) Per IWG 2006 Criteria
Per IWG 2006 response criteria, HI-N was defined as the neutrophil increase in any rolling 8 weeks is at last 100% and an absolute increase \> 0.5 x 10\^9/L. The rolling 8-week was defined as any consecutive 8 weeks during the study. The percentage of participants with HI-N response were reported.
Time frame: Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)
Duration of HI-E Per IWG 2006 Response Criteria
Per IWG 2006 response criteria, duration of HI-E response was defined as the time from the first day of the first rolling 8-week interval of showing response to the last day of the last consecutive rolling 8-week interval of showing response. HI-E response for LTB participants was defined as hemoglobin increase ≥ 1.5 g/dL during any rolling 8-week window and for HTB HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study.
Time frame: up to approximately 75 weeks
Time to HI-E Per IWG 2006 Response Criteria
Per IWG 2006 response criteria, the time to HI-E response was defined as the first date of the rolling 8-week interval of showing response minus first dose date plus 1. HI-E response for LTB participants was defined as hemoglobin increase ≥ 1.5 g/dL during any rolling 8 weeks window and for HTB HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study.
Time frame: Any consecutive 8 weeks during the study (up to approximately 75 weeks)
Mean Change From Baseline to Day 113 in Frequency of RBC Transfusions
Frequency of RBC transfusion was defined as the total number of RBC transfusions received. Per protocol, the mean change from baseline to Day 113 in frequency of RBC transfusion was reported in the HTB participants (those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline).
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Rate of RBC Transfusion Independence (RBC-TI)
Rate of RBC-TI was defined as percentage of participants with ≥2 units of RBC transfusions at baseline who experienced transfusion independence which was defined as ≥8 weeks without a transfusion while on treatment. Per protocol, rate of RBC-TI was reported in HTB participants (those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline).
Time frame: Up to approximately 16 weeks
Time to Maximum Concentration (Tmax) of Luspatercept
Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as time to the maximum concentration of luspatercept reached. Tmax was based on non-compartmental analysis and a mean Tmax value was presented.
Time frame: Cycle 1 Day 1: Predose, Cycle 1: Days 8, 11, 15: Postdose; Cycle 2 Day 1, Cycle 2 Day 8, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 5 Days 8, 15: Postdose (each cycle length = 21 days)
Terminal Half-Life (t ½) of Luspatercept
Blood samples were collected at specified intervals for the determination of t½. t½ was defined as the time required to divide the luspatercept plasma concentration by two after reaching pseudo-equilibrium, following a single dose of luspatercept. t½ was based on non-compartmental analysis and a mean t1/2 value was presented.
Time frame: Cycle 1 Day 1: Predose, Cycle 1: Days 8, 11, 15: Postdose; Cycle 2 Day 1, Cycle 2 Day 8, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 5 Days 8, 15: Postdose (each cycle length = 21 days)
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 reached. Cmax was based on non-compartmental analysis and a mean Cmax value was presented.
Time frame: Cycle 1 Day 1: Predose, Cycle 1: Days 8, 11, 15: Postdose; Cycle 2 Day 1, Cycle 2 Day 8, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 5 Days 8, 15: Postdose (each cycle length = 21 days)
Area Under the Concentration-Time Curve of Luspatercept From Time 0 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 Study Day 21. AUC0-21 was based on non-compartmental analysis and a mean AUC0-21 value was presented.
Time frame: Cycle 1 Day 1: Predose, Cycle 1 Days 8, 11, 15 and Cycle 2 Day 1: Postdose (each cycle length = 21 days)
Percent Change From Baseline to Day 113 in Concentration of Serum Iron
Blood samples were to be collected at pre-specified time intervals to determine serum iron concentration. Baseline was prespecified to be the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Total Iron Binding Capacity (TIBC)
Blood samples were collected at pre-specified time intervals to determine TIBC. The percentage change from baseline in TIBC was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Transferrin
Blood samples were to be collected at pre-specified time intervals to determine concentration of transferrin. Baseline was prespecified to be the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Soluble Transferrin Receptor
Blood samples were collected at pre-specified time intervals to determine soluble transferrin receptor concentration. The percentage change from baseline in concentration of soluble transferrin receptor was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Serum Ferritin
Blood samples were collected at pre-specified time intervals to determine serum ferritin concentration. The percentage change from baseline in concentration of serum ferritin was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Non-Transferrin Bound Iron (NTBI)
Blood samples were to be collected at pre-specified time intervals to determine concentration of NTBI. Baseline was prespecified to be the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Serum Hepcidin
Blood samples were collected at pre-specified time intervals to determine soluble hepcidin concentration. The percentage change from baseline in concentration of soluble hepcidin was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Serum Erythropoietin
Blood samples were collected at pre-specified time intervals to determine serum erythropoietin concentration. The percentage change from baseline in concentration of serum erythropoietin was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Reticulocyte Count
Blood samples were collected at pre-specified time intervals to determine reticulocyte count. The percentage change from baseline in mean reticulocyte count was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Direct Bilirubin Level
Blood samples were collected at pre-specified time intervals to determine serum direct bilirubin concentration. The percentage change from baseline in mean concentration direct bilirubin was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Total Bilirubin Level
Blood samples were collected at pre-specified time intervals to determine total bilirubin concentration. The percentage change from baseline in mean concentration total bilirubin was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Lactate Dehydrogenase Level
Blood samples were collected at pre-specified time intervals to determine serum lactate dehydrogenase level. The percentage change from baseline in mean concentration lactate dehydrogenase level was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Nucleated RBC (nRBC)
Blood samples were to be collected at pre-specified time intervals to determine concentration of nRBC. Baseline was prespecified to be the last measurement prior to the first dose of study drug.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP)
Blood samples were collected at pre-specified time intervals to determine serum BSAP concentration. The percentage change from baseline in concentration BSAP was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113
Percent Change From Baseline to Day 113 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX)
Blood samples were collected at pre-specified time intervals to determine serum CTX. The percentage change from baseline in concentration of CTX was reported.
Time frame: Baseline (prior to first dose of luspatercept) and Day 113

Results

Posted Jul 29, 2024

Participant flow

Participant flow — Overall Study
Milestone	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Started	3	3	3	6	3	6	3	89
Completed	3	3	3	6	3	5	3	82
Not completed	0	0	0	0	0	1	0	7
Withdrew: Lost to follow-up	0	0	0	0	0	0	0	1
Withdrew: Withdrawal by subject	0	0	0	0	0	1	0	1
Withdrew: Not reported	0	0	0	0	0	0	0	5

Outcome measures

PrimaryPercentage of Low Transfusion Burden (LTB) Participants With Modified Erythroid Response (mHI-E)

The mHI-E for LTB participants was defined as a hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 days or rolling 2 weeks (in the absence of red blood cell \[RBC\] transfusions). Hemoglobin measurements within 7 days following RBC transfusion were excluded from analysis. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Rolling 2 weeks was defined as any consecutive 2 weeks during the study. The percentage of LTB participants with mHI-E were reported.

Time frame:: Any consecutive 2 weeks during the study (up to approximately 75 weeks)
Reported as:: Number · Percentage of participants

Percentage of Low Transfusion Burden (LTB) Participants With Modified Erythroid Response (mHI-E)
Percentage of participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percentage of Low Transfusion Burden (LTB) Participants With Modified Erythroid Response (mHI-E)	0 (0 to 97.5)	0 (0 to 97.5)	—	66.7 (9.4 to 99.2)	—	—	100 (15.8 to 100)	69.0 (55.5 to 80.5)

PrimaryPercentage of High Transfusion Burden (HTB) Participants With mHI-E

The mHI-E for HTB participants was defined as a ≥4 units or ≥50% reduction in RBC transfusion burden during any rolling 8-week window compared to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. The percentage of HTB participants with mHI-E were reported.

Time frame:: Any consecutive 8 weeks during the study (up to approximately 75 weeks)
Reported as:: Number · Percentage of Participants

Percentage of High Transfusion Burden (HTB) Participants With mHI-E
Percentage of Participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percentage of High Transfusion Burden (HTB) Participants With mHI-E	50.0 (1.26 to 98.7)	50.0 (1.26 to 98.7)	33.3 (0.84 to 90.6)	33.3 (0.84 to 90.6)	33.3 (0.84 to 90.6)	50.0 (11.8 to 88.2)	100 (2.5 to 100)	54.8 (36.0 to 72.7)

SecondaryNumber of Participants Who Experienced an Adverse Event (AE)

An adverse event (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 can 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 were reported.

Time frame:: Up to approximately 24 weeks
Reported as:: Count of participants · Participants

Number of Participants Who Experienced an Adverse Event (AE)
Participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Number of Participants Who Experienced an Adverse Event (AE)	1	2	3	5	3	4	2	75

SecondaryNumber of Participants Who Discontinued Study Treatment Due To an AE

Time frame:: Up to approximately 12 weeks
Reported as:: Count of participants · Participants

Number of Participants Who Discontinued Study Treatment Due To an AE
Participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Number of Participants Who Discontinued Study Treatment Due To an AE	0	0	0	0	0	0	0	5

SecondaryRate of Erythroid Response (HI-E) Per International Working Group (IWG) 2006 Response Criteria

Per IWG 2006 response criteria, rate of HI-E is defined as the percentage of participants for whom the mean of all hemoglobin value from baseline during any rolling 8-week increased ≥1.5 g/dL in the absence of transfusion for LTB participants, or a reduction by ≥4 units of RBCs transfusion over any rolling 8-week window for HTB patients. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. Rolling 8 weeks was defined as any consecutive 8 weeks during the study.

Time frame:: Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)
Reported as:: Number · Percentage of participants

Rate of Erythroid Response (HI-E) Per International Working Group (IWG) 2006 Response Criteria
Percentage of participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Rate of Erythroid Response (HI-E) Per International Working Group (IWG) 2006 Response Criteria	33.3 (0.8 to 90.6)	0 (0.0 to 70.8)	33.3 (0.8 to 90.6)	33.3 (4.3 to 77.7)	33.3 (0.8 to 90.6)	50.0 (11.8 to 88.2)	100 (29.2 to 100)	53.9 (43.0 to 64.6)

SecondaryRate of Platelet Response (HI-P) Per IWG 2006 Criteria

Per IWG 2006 response criteria, HI-P was defined for participants with baseline value ≥20 x 10\^9/L as the platelet increase in any rolling 8 weeks ≥30 x 10\^9 and for participants with baseline value \<20 x 10\^9/L as the platelet increase in any rolling 8 weeks \>20 x 10\^9/L with increase of at least 100%. The rolling 8-week was defined as any consecutive 8 weeks during the study. The percentage of participants with HI-P were reported.

Time frame:: Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)
Reported as:: Number · Percentage of participants

Rate of Platelet Response (HI-P) Per IWG 2006 Criteria
Percentage of participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Rate of Platelet Response (HI-P) Per IWG 2006 Criteria	—	—	0 ± 0.0	—	0 ± 0.0	0 ± 0.0	—	23.5 ± 6.8

SecondaryRate of Neutrophil Response (HI-N) Per IWG 2006 Criteria

Per IWG 2006 response criteria, HI-N was defined as the neutrophil increase in any rolling 8 weeks is at last 100% and an absolute increase \> 0.5 x 10\^9/L. The rolling 8-week was defined as any consecutive 8 weeks during the study. The percentage of participants with HI-N response were reported.

Time frame:: Any consecutive 8 Weeks during the study treatment (up to approximately 75 weeks)
Reported as:: Number · Percentage of Participants

Rate of Neutrophil Response (HI-N) Per IWG 2006 Criteria
Percentage of Participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Rate of Neutrophil Response (HI-N) Per IWG 2006 Criteria	0 (0.0 to 97.5)	—	100 (2.5 to 100)	0 (0.0 to 97.5)	—	66.7 (9.4 to 99.2)	100 (2.5 to 100)	25.0 (8.7 to 49.1)

SecondaryDuration of HI-E Per IWG 2006 Response Criteria

Per IWG 2006 response criteria, duration of HI-E response was defined as the time from the first day of the first rolling 8-week interval of showing response to the last day of the last consecutive rolling 8-week interval of showing response. HI-E response for LTB participants was defined as hemoglobin increase ≥ 1.5 g/dL during any rolling 8-week window and for HTB HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study.

Time frame:: up to approximately 75 weeks
Reported as:: Mean · Days

Duration of HI-E Per IWG 2006 Response Criteria
Days	Low Dose Luspatercept 0.125-0.5 mg/kg (Cohorts 1, 2, 3)	High Dose Luspatercept 0.75-1.75mg/kg (Cohorts 4, 5, 6, 7 & Expansion)
Duration of HI-E Per IWG 2006 Response Criteria	78 ± 7.8	88 ± 22.8

SecondaryTime to HI-E Per IWG 2006 Response Criteria

Per IWG 2006 response criteria, the time to HI-E response was defined as the first date of the rolling 8-week interval of showing response minus first dose date plus 1. HI-E response for LTB participants was defined as hemoglobin increase ≥ 1.5 g/dL during any rolling 8 weeks window and for HTB HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study.

Time frame:: Any consecutive 8 weeks during the study (up to approximately 75 weeks)
Reported as:: Mean · Days

Time to HI-E Per IWG 2006 Response Criteria
Days	Low Dose Luspatercept 0.125-0.5 mg/kg (Cohorts 1, 2, 3)	High Dose Luspatercept 0.75-1.75mg/kg (Cohorts 4, 5, 6, 7 & Expansion)
Time to HI-E Per IWG 2006 Response Criteria	35 ± 48.1	17 ± 18.3

SecondaryMean Change From Baseline to Day 113 in Frequency of RBC Transfusions

Frequency of RBC transfusion was defined as the total number of RBC transfusions received. Per protocol, the mean change from baseline to Day 113 in frequency of RBC transfusion was reported in the HTB participants (those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline).

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Number of RBC transfusions

Mean Change From Baseline to Day 113 in Frequency of RBC Transfusions
Number of RBC transfusions	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Baseline	2.50 ± 0.71	2.50 ± 2.12	4.00 ± 0.00	2.00 ± 0.00	4.00 ± 1.00	2.83 ± 0.75	3.00 ± NA	3.06 ± 1.34
Baseline to Day 113	-0.70 ± 0.71	0.11 ± 0.69	0.38 ± 2.08	0.40 ± 2.12	-0.31 ± 1.21	-0.36 ± 1.03	-2.46 ± NA	-0.85 ± 1.14

SecondaryRate of RBC Transfusion Independence (RBC-TI)

Rate of RBC-TI was defined as percentage of participants with ≥2 units of RBC transfusions at baseline who experienced transfusion independence which was defined as ≥8 weeks without a transfusion while on treatment. Per protocol, rate of RBC-TI was reported in HTB participants (those who required ≥4 units of RBC transfusions within 8 weeks prior to baseline).

Time frame:: Up to approximately 16 weeks
Reported as:: Number · Percentage of participants

Rate of RBC Transfusion Independence (RBC-TI)
Percentage of participants	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Rate of RBC Transfusion Independence (RBC-TI)	50.0 (1.3 to 98.7)	0.0 (0.0 to 84.2)	0.0 (0.0 to 70.8)	66.7 (22.3 to 95.7)	0 (0.0 to 70.8)	33.3 (4.3 to 77.7)	100 (2.5 to 100)	43.9 (30.7 to 57.6)

SecondaryTime to Maximum Concentration (Tmax) of Luspatercept

Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as time to the maximum concentration of luspatercept reached. Tmax was based on non-compartmental analysis and a mean Tmax value was presented.

Time frame:: Cycle 1 Day 1: Predose, Cycle 1: Days 8, 11, 15: Postdose; Cycle 2 Day 1, Cycle 2 Day 8, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 5 Days 8, 15: Postdose (each cycle length = 21 days)
Reported as:: Geometric mean · Days

Time to Maximum Concentration (Tmax) of Luspatercept
Days	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Time to Maximum Concentration (Tmax) of Luspatercept	9.93 ± 35.73	7.23 ± 20.68	10.16 ± 39.56	7.16 ± 5.46	7.23 ± 20.68	8.47 ± 31.58	6.65 ± 8.92	7.77 ± 21.76

SecondaryTerminal Half-Life (t ½) of Luspatercept

Blood samples were collected at specified intervals for the determination of t½. t½ was defined as the time required to divide the luspatercept plasma concentration by two after reaching pseudo-equilibrium, following a single dose of luspatercept. t½ was based on non-compartmental analysis and a mean t1/2 value was presented.

Time frame:: Cycle 1 Day 1: Predose, Cycle 1: Days 8, 11, 15: Postdose; Cycle 2 Day 1, Cycle 2 Day 8, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 5 Days 8, 15: Postdose (each cycle length = 21 days)
Reported as:: Geometric mean · Days

Terminal Half-Life (t ½) of Luspatercept
Days	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Terminal Half-Life (t ½) of Luspatercept	23.78 ± 22.29	9.15 ± 44.83	15.14 ± 5.94	14.45 ± 16.02	13.75 ± 7.37	14.76 ± 24.43	26.56 ± 9.19	14.74 ± 44.35

SecondaryMaximum 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 reached. Cmax was based on non-compartmental analysis and a mean Cmax value was presented.

Time frame:: Cycle 1 Day 1: Predose, Cycle 1: Days 8, 11, 15: Postdose; Cycle 2 Day 1, Cycle 2 Day 8, Cycle 4 Day 1, Cycle 5 Day 1, and Cycle 5 Days 8, 15: Postdose (each cycle length = 21 days)
Reported as:: Geometric mean · ug/mL

Maximum Concentration (Cmax) of Luspatercept
ug/mL	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Maximum Concentration (Cmax) of Luspatercept	0.64 ± 34.88	0.96 ± 92.99	2.33 ± 27.16	3.76 ± 42.29	4.35 ± 12.87	7.46 ± 14.55	9.66 ± 7.52	5.73 ± 26.93

SecondaryArea Under the Concentration-Time Curve of Luspatercept From Time 0 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 Study Day 21. AUC0-21 was based on non-compartmental analysis and a mean AUC0-21 value was presented.

Time frame:: Cycle 1 Day 1: Predose, Cycle 1 Days 8, 11, 15 and Cycle 2 Day 1: Postdose (each cycle length = 21 days)
Reported as:: Geometric mean · day*ug/m

Area Under the Concentration-Time Curve of Luspatercept From Time 0 to Day 21 (AUC0-21)
day*ug/m	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Area Under the Concentration-Time Curve of Luspatercept From Time 0 to Day 21 (AUC0-21)	9.29 ± 32.16	12.56 ± 94.99	36.90 ± 4.19	51.82 ± 35.93	62.46 ± 25.20	112.56 ± 17.00	137.56 ± 1.13	80.02 ± 27.77

SecondaryPercent Change From Baseline to Day 113 in Concentration of Serum Iron

Blood samples were to be collected at pre-specified time intervals to determine serum iron concentration. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 113 in Total Iron Binding Capacity (TIBC)

Blood samples were collected at pre-specified time intervals to determine TIBC. The percentage change from baseline in TIBC was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Total Iron Binding Capacity (TIBC)
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Total Iron Binding Capacity (TIBC)	-1.49 ± 8.940	1.61 ± 1.392	-6.70 ± 6.050	10.91 ± 11.806	7.46 ± 11.727	-12.27 ± 22.144	-4.16 ± 2.435	-2.40 ± 9.916

SecondaryPercent Change From Baseline to Day 113 in Concentration of Transferrin

Blood samples were to be collected at pre-specified time intervals to determine concentration of transferrin. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 113 in Concentration of Soluble Transferrin Receptor

Blood samples were collected at pre-specified time intervals to determine soluble transferrin receptor concentration. The percentage change from baseline in concentration of soluble transferrin receptor was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Concentration of Soluble Transferrin Receptor
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Concentration of Soluble Transferrin Receptor	60.88 ± 76.427	-31.46 ± 5.135	-4.62 ± 6.527	36.35 ± 21.718	—	-17.11 ± 32.861	19.25 ± 7.793	35.35 ± 44.228

SecondaryPercent Change From Baseline to Day 113 in Concentration of Serum Ferritin

Blood samples were collected at pre-specified time intervals to determine serum ferritin concentration. The percentage change from baseline in concentration of serum ferritin was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Concentration of Serum Ferritin
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Concentration of Serum Ferritin	-19.55 ± 32.845	58.63 ± 24.342	74.31 ± 160.308	1.16 ± 23.487	19.38 ± 25.666	8.56 ± 41.532	-16.07 ± 27.172	-1.51 ± 46.269

SecondaryPercent Change From Baseline to Day 113 in Concentration of Non-Transferrin Bound Iron (NTBI)

Blood samples were to be collected at pre-specified time intervals to determine concentration of NTBI. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 113 in Concentration of Serum Hepcidin

Blood samples were collected at pre-specified time intervals to determine soluble hepcidin concentration. The percentage change from baseline in concentration of soluble hepcidin was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Concentration of Serum Hepcidin
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Concentration of Serum Hepcidin	-42.40 ± 5.907	6.56 ± 35.740	-14.55 ± 39.855	-15.62 ± 20.814	-5.54 ± 49.144	65.41 ± 179.249	-64.51 ± NA	30.15 ± 143.118

SecondaryPercent Change From Baseline to Day 113 in Concentration of Serum Erythropoietin

Blood samples were collected at pre-specified time intervals to determine serum erythropoietin concentration. The percentage change from baseline in concentration of serum erythropoietin was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Concentration of Serum Erythropoietin
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Concentration of Serum Erythropoietin	144.48 ± 232.336	110.51 ± 85.751	122.85 ± 163.500	1.81 ± 48.208	749.10 ± 902.000	146.49 ± 160.087	29.07 ± 80.426	238.85 ± 974.226

SecondaryPercent Change From Baseline to Day 113 in Reticulocyte Count

Blood samples were collected at pre-specified time intervals to determine reticulocyte count. The percentage change from baseline in mean reticulocyte count was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Reticulocyte Count
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Reticulocyte Count	110.82 ± 127.489	8.10 ± NA	79.77 ± 45.816	28.29 ± 28.434	76.16 ± 54.003	0.45 ± 19.770	84.06 ± 108.298	41.37 ± 73.445

SecondaryPercent Change From Baseline to Day 113 in Direct Bilirubin Level

Blood samples were collected at pre-specified time intervals to determine serum direct bilirubin concentration. The percentage change from baseline in mean concentration direct bilirubin was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Direct Bilirubin Level
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Direct Bilirubin Level	-18.45 ± 6.569	12.38 ± 38.465	2.33 ± NA	7.22 ± 20.592	-5.00 ± NA	-7.41 ± 12.830	6.78 ± NA	-0.50 ± 27.541

SecondaryPercent Change From Baseline to Day 113 in Total Bilirubin Level

Blood samples were collected at pre-specified time intervals to determine total bilirubin concentration. The percentage change from baseline in mean concentration total bilirubin was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Total Bilirubin Level
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Total Bilirubin Level	-25.41 ± 5.596	4.32 ± 26.094	47.43 ± 51.076	4.02 ± 10.439	-25.08 ± 17.240	-25.84 ± 19.893	10.68 ± 20.258	13.26 ± 37.239

SecondaryPercent Change From Baseline to Day 113 in Lactate Dehydrogenase Level

Blood samples were collected at pre-specified time intervals to determine serum lactate dehydrogenase level. The percentage change from baseline in mean concentration lactate dehydrogenase level was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Lactate Dehydrogenase Level
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Lactate Dehydrogenase Level	13.09 ± 28.850	-10.28 ± 6.589	0.03 ± 32.694	2.76 ± 7.848	-15.20 ± 25.355	-2.52 ± 18.669	-11.91 ± 35.318	20.58 ± 46.589

SecondaryPercent Change From Baseline to Day 113 in Nucleated RBC (nRBC)

Blood samples were to be collected at pre-specified time intervals to determine concentration of nRBC. Baseline was prespecified to be the last measurement prior to the first dose of study drug.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 113 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP)

Blood samples were collected at pre-specified time intervals to determine serum BSAP concentration. The percentage change from baseline in concentration BSAP was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP)
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP)	-6.41 ± 3.698	-36.70 ± 9.430	-24.60 ± 16.413	47.48 ± 42.431	14.15 ± 13.191	-6.43 ± 25.559	15.27 ± NA	8.31 ± 23.800

SecondaryPercent Change From Baseline to Day 113 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX)

Blood samples were collected at pre-specified time intervals to determine serum CTX. The percentage change from baseline in concentration of CTX was reported.

Time frame:: Baseline (prior to first dose of luspatercept) and Day 113
Reported as:: Mean · Percent change

Percent Change From Baseline to Day 113 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX)
Percent change	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort
Percent Change From Baseline to Day 113 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX)	-4.42 ± NA	—	16.26 ± NA	26.37 ± 24.669	15.94 ± 35.018	13.04 ± 62.513	-70.97 ± NA	22.66 ± 51.177

Adverse events

Collected over Up to approximately 75 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Luspatercept 0.125 mg/kg (Cohort 1)	0/3 (0%)	1/3 (33.3%)	1/3 (33.3%)
Luspatercept 0.25 mg/kg (Cohort 2)	0/3 (0%)	0/3 (0%)	2/3 (66.7%)
Luspatercept 0.50 mg/kg (Cohort 3)	0/3 (0%)	0/3 (0%)	3/3 (100%)
Luspatercept 0.75 mg/kg (Cohort 4)	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Luspatercept 1.0 mg/kg (Cohort 5)	0/3 (0%)	1/3 (33.3%)	3/3 (100%)
Luspatercept 1.33 mg/kg (Cohort 6)	0/6 (0%)	3/6 (50%)	3/6 (50%)
Luspatercept 1.75 mg/kg (Cohort 7)	0/3 (0%)	1/3 (33.3%)	2/3 (66.7%)
Expansion Cohort	0/89 (0%)	14/89 (15.7%)	62/89 (69.7%)

Most frequent serious events

Showing 10 of 22

Most frequent serious events
Event	Luspatercept 0.125 mg/kg (Cohort 1)	Luspatercept 0.25 mg/kg (Cohort 2)	Luspatercept 0.50 mg/kg (Cohort 3)	Luspatercept 0.75 mg/kg (Cohort 4)	Luspatercept 1.0 mg/kg (Cohort 5)	Luspatercept 1.33 mg/kg (Cohort 6)	Luspatercept 1.75 mg/kg (Cohort 7)	Expansion Cohort
Cholecystitis acuteHepatobiliary disorders	0/3	0/3	0/3	0/6	1/3	0/6	0/3	0/89
Rib fractureInjury, poisoning and procedural complications	1/3	0/3	0/3	0/6	0/3	0/6	0/3	0/89
HaemarthrosisMusculoskeletal and connective tissue disorders	0/3	0/3	0/3	0/6	0/3	0/6	1/3	0/89
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders	0/3	0/3	0/3	0/6	0/3	0/6	1/3	0/89
AnaemiaBlood and lymphatic system disorders	0/3	0/3	0/3	0/6	0/3	1/6	0/3	1/89
Clostridium difficile colitisInfections and infestations	0/3	0/3	0/3	0/6	0/3	1/6	0/3	0/89
BursitisMusculoskeletal and connective tissue disorders	0/3	0/3	0/3	0/6	0/3	1/6	0/3	0/89
Aortic valve stenosisCardiac disorders	0/3	0/3	0/3	0/6	0/3	0/6	0/3	1/89
ColitisGastrointestinal disorders	0/3	0/3	0/3	0/6	0/3	0/6	0/3	1/89
General physical health deteriorationGeneral disorders	0/3	0/3	0/3	0/6	0/3	0/6	0/3	1/89

Most frequent other events

Showing 10 of 74

Most frequent other events
Event	Luspatercept 0.125 mg/kg (Cohort 1)	Luspatercept 0.25 mg/kg (Cohort 2)	Luspatercept 0.50 mg/kg (Cohort 3)	Luspatercept 0.75 mg/kg (Cohort 4)	Luspatercept 1.0 mg/kg (Cohort 5)	Luspatercept 1.33 mg/kg (Cohort 6)	Luspatercept 1.75 mg/kg (Cohort 7)	Expansion Cohort
Lumbar vertebral fractureInjury, poisoning and procedural complications	0/3	0/3	0/3	0/6	2/3	0/6	0/3	0/89
Bone painMusculoskeletal and connective tissue disorders	0/3	0/3	1/3	0/6	2/3	0/6	0/3	5/89
Muscle spasmsMusculoskeletal and connective tissue disorders	0/3	0/3	2/3	0/6	1/3	0/6	1/3	1/89
FatigueGeneral disorders	0/3	0/3	0/3	0/6	0/3	3/6	0/3	11/89
AnaemiaBlood and lymphatic system disorders	0/3	0/3	0/3	0/6	0/3	0/6	1/3	3/89
LeukopeniaBlood and lymphatic system disorders	0/3	0/3	0/3	0/6	1/3	0/6	0/3	0/89
Red blood cell abnormalityBlood and lymphatic system disorders	0/3	0/3	0/3	0/6	1/3	0/6	0/3	0/89
Atrial fibrillationCardiac disorders	1/3	0/3	0/3	0/6	0/3	0/6	0/3	0/89
Abdominal pain lowerGastrointestinal disorders	0/3	0/3	0/3	0/6	1/3	0/6	0/3	0/89
Abdominal pain upperGastrointestinal disorders	0/3	0/3	1/3	0/6	1/3	0/6	0/3	4/89

Baseline characteristics

All enrolled participants

Age, Continuous
Age, Continuous(years)	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort	Total
Mean	70.0 ± 19.1	59.0 ± 27.8	66.3 ± 5.1	64.8 ± 11.3	73.7 ± 3.8	68.2 ± 7.1	63.7 ± 19.6	71.6 ± 9.6	70.4 ± 10.7

Sex: Female, Male
Sex: Female, Male(Participants)	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort	Total
Female	3	3	2	3	0	1	2	30	44
Male	0	0	1	3	3	5	1	59	72

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort	Total
Hispanic or Latino	0	0	0	0	0	0	0	0	0
Not Hispanic or Latino	3	2	3	6	3	5	3	80	105
Unknown or Not Reported	0	1	0	0	0	1	0	9	11

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort	Total
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0
White	3	3	3	6	3	6	3	89	116
More than one race	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0

Transfusion Status
Transfusion Status(Participants)	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort	Total
HTB	2	2	3	3	3	6	1	31	51
LTB	1	1	0	3	0	0	2	58	65

Hemoglobin level
Hemoglobin level(g/dl)	Luspatercept 0.125mg/kg (Cohort 1)	Luspatercept 0.25mg/kg (Cohort 2)	Luspatercept 0.50mg/kg (Cohort 3)	Luspatercept 0.75mg/kg (Cohort 4)	Luspatercept 1.00mg/kg (Cohort 5)	Luspatercept 1.33mg/kg (Cohort 6)	Luspatercept 1.75mg/kg (Cohort 7)	Expansion Cohort	Total
Mean	10.30 ± 0.98	8.91 ± 0.81	8.83 ± 0.31	8.55 ± 0.75	8.37 ± 1.10	8.42 ± 0.58	9.53 ± 0.06	8.79 ± 1.01	8.81 ± 0.98

Study locations

1 site

Acceleron Investigative Site
Dresden, Germany

References and documents

Publications

Platzbecker U, Gotze KS, Kiewe P, Germing U, Mayer K, Radsak M, Wolff T, Chromik J, Sockel K, Oelschlagel U, Haase D, Illmer T, Al-Ali HK, Silling G, Reynolds JG, Zhang X, Attie KM, Shetty JK, Giagounidis A. Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study. J Clin Oncol. 2022 Nov 20;40(33):3800-3807. doi: 10.1200/JCO.21.02476. Epub 2022 Aug 23. PubMed 35998303 ↗
Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, Radsak M, Wolff T, Zhang X, Laadem A, Sherman ML, Attie KM, Giagounidis A. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017 Oct;18(10):1338-1347. doi: 10.1016/S1470-2045(17)30615-0. Epub 2017 Sep 1. Erratum In: Lancet Oncol. 2017 Oct;18(10):e562. doi: 10.1016/S1470-2045(17)30723-4. PubMed 28870615 ↗

Study documents

Study protocol · Jul 5, 2016
Statistical analysis plan · Feb 19, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 29, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01749514
Lead sponsor: Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Responsible party: Sponsor
First posted: Dec 13, 2012
Start date: Jan 21, 2013
Primary completion: Oct 22, 2018
Completion: Oct 22, 2018
Results posted: Jul 29, 2024
Last update: Jul 29, 2024

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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