ClinicalTrials.gg
Sign In
CompletedNCT02268383Updated Jul 29, 2024Results posted

Extension Study to Evaluate Long-Term Effects of Luspatercept in Patients With Myelodysplastic Syndromes (MDS) (A536-05/MK-6143-003)

A Phase 2 interventional study of Luspatercept in Myelodysplastic Syndromes, 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 (part of Merck & Co., Inc) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
75
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This study is an open-label extension study for participants previously enrolled in study MK-6143-001 (formerly called A536-03, ClinicalTrials.gov Identifier NCT01749514), to evaluate the long-term safety and tolerability of luspatercept (MK-6143) in participants with low or intermediate-1 risk MDS.

Read the detailed description

This study is an open-label extension study to evaluate the safety, tolerability, and pharmacodynamic effects of up to 24 months of luspatercept treatment in participants with low or intermediate-1 risk myelodysplastic syndromes previously treated with luspatercept for up to 3 months in MK-6143-001 study (NCT01749514). The starting dose level in this study will be 1.0 mg/kg by subcutaneous (SC) injection every 3 weeks. Dose titration/modification rules will be followed for individual participants and will be based upon safety and efficacy data collected during the course of treatment.

02

Conditions studied

  • Myelodysplastic Syndromes
03

In context

Myelodysplastic Syndromes

2,165 studies on the registry are indexed under Myelodysplastic Syndromes; 322 are open to participants now.

This study's enrollment of 75 is above the median of 39 across 1,771 interventional studies indexed under Myelodysplastic Syndromes.

Browse Myelodysplastic Syndromes studies →

Lead sponsor

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA is the lead sponsor of 26 studies on the registry; none are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 8 (89%) have results posted.

First submitted before Acceleron Pharma, Inc. became part of Merck & Co., Inc.

Browse Acceleron Pharma, Inc. studies →All Merck & Co., Inc studies →

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

04

Who can participate

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Completion of the treatment period in the base study MK-6143-001 (ClinicalTrials.gov Identifier: NCT01749514)
  • Adequate birth control measures
  • Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements
  • Patient understands and is able to provide written informed consent

  • In addition, patients with treatment interruption (defined as patients who complete their end-of-study visit in MK-6143-001 and cannot directly roll over to MK-6143-003) must also meet the following criteria:

    • Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) criteria 16 (white blood count (WBC) \< 13,000/μL) 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), for non-transfusion dependent (NTD) patients (defined as having received ˂ 4 units of red blood cells (RBCs) within 8 weeks prior to Cycle 1 Day 1), OR
    • Transfusion Dependent (TD), defined as having received ≥ 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1
  • Platelet count ≥ 30 x 109/L
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia)
  • Adequate renal (creatinine ≤ 2.0 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

Exclusion criteria

Exclusion Criteria:

  • Discontinuation/withdrawal from the base study A536-03 (due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication [e.g. azacitidine], medical reason or adverse event (AE), hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up) prior to completion of the treatment period
  • Prior treatment with azacitidine or decitabine

  • Treatment within 28 days prior to Cycle 1 Day 1 with:

    • An 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 (including sotatercept [ACE-011]) 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
  • 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
  • Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV)
  • Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or diastolic blood pressure (DBP) ≥ 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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
75 participants (actual)

Study arms

  • Experimental
    Luspatercept Extension population

    Luspatercept 1.0 mg/kg once every 3 weeks by subcutaneous injection.

    Drug: Luspatercept

Interventions

  • DrugLuspatercept

    Luspatercept 1.0 mg/kg once every 3 weeks by subcutaneous injection.

    Also known as: MK-6143, ACE-536

06

What researchers measure

Primary outcomes

  1. 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 was reported.

    Time frame: Up to approximately 5 years

  2. 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 luspatercept due to an AE was reported.

    Time frame: Up to approximately 5 years

Secondary outcomes

  1. Percentage of Participants With Modified Erythroid Response (mHI-E) Per International Working Group (IWG) 2006 Response Criteria

    The mHI-E was defined as a mean hemoglobin (Hgb) increase ≥1.5 g/dL over an 8-week period as compared to baseline, not influenced by red blood cell (RBC) transfusion in low transfusion burden (LTB) participants and a decrease of ≥4 units or ≥50% of units of RBCs transfused over a period of 8 weeks, relative to the number of units of RBCs transfused in the 8 weeks immediately prior to baseline in high transfusion burden (HTB) participants. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 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 (up to approximately 5 years)

  2. Rate of Erythroid Response (HI-E) Per IWG 2006 Response Criteria

    Per IWG 2006 response criteria, the rate of HI-E was defined as the percentage of participants with an HI-E response by an Hgb increase of ≥1.5 g/dL for participants not transfused or as defined by having received less than 4 units of RBCs within 8 weeks of baseline or reduction by ≥4 units of RBCs transfused (for a Hgb≤9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study day 1.

    Time frame: Any consecutive 8 weeks during the study (up to approximately 5 years)

  3. Rate of Neutrophil Response (HI-N) Per IWG 2006 Response Criteria

    Per IWG 2006 response criteria, HI-N response was defined for participants with baseline absolute neutrophil count (ANC) \<1.0×10\^9/L as the percentage increase ≥100% and an absolute mean increase \>0.5 ×10\^9/L during any rolling 8-week window on treatment compared with baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study. Percentage of participants with HI-N response were reported.

    Time frame: Any consecutive 8 Weeks during the study (up to approximately 5 years)

  4. Rate of Platelet Response (HI-P) Per IWG 2006 Response Criteria

    Per IWG 2006 response criteria, HI-P response was defined for participants with baseline platelet count \<100×10\^9/L as the following: 1) For participants with baseline ≥20×10\^9/L, an absolute increase of ≥30×10\^9/L during any rolling 8-week window on treatment and 2) For participants with baseline \<20×10\^9/L, mean value of \>20×10\^9/L and percentage increase ≥100% during any rolling 8-week window on treatment. The rolling 8-week was defined as any consecutive 8 weeks during the study. Percentage of participants with HI-P response were reported.

    Time frame: Any consecutive 8 Weeks during the study (up to approximately 5 years)

  5. Duration of HI-E in LTB Participants Per IWG 2006 Response Criteria

    For LTB participants, HI-E was defined as all Hgb increase ≥1.5 g/dL during any rolling 8 weeks window. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Per IWG 2006 response criteria, duration of HI-E was defined as the time from the first day of the first rolling 8 weeks interval of showing response to the last day of the last consecutive rolling 8 weeks interval of showing response. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

    Time frame: up to approximately 5 years

  6. Duration of HI-E in HTB Participants Per IWG 2006 Response Criteria

    For HTB participants, HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Per IWG 2006 response criteria, duration of HI-E was defined as the time from the first day of the first rolling 8 weeks interval of showing response to the last day of the last consecutive rolling 8 weeks interval of showing response. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

    Time frame: up to approximately 5 years

  7. Time to HI-E in LTB Participants Per IWG 2006 Response Criteria

    For LTB participants, HI-E was defined as all Hgb increase ≥1.5 g/dL during any rolling 8 weeks window. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Per IWG 2006 response criteria, time to HI-E was defined as the first date of the rolling 8 weeks interval of showing response minus first dose date plus 1. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

    Time frame: up to approximately 5 years

  8. Time to HI-E in HTB Participants Per IWG 2006 Response Criteria

    For HTB participants, HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Per IWG 2006 response criteria, time to HI-E was defined as the first date of the rolling 8 weeks interval of showing response minus first dose date plus 1. Rolling 8 weeks was defined as any consecutive 8 weeks during the study.

    Time frame: Any consecutive 8 weeks during the study (up to approximately 5 years)

  9. Rate of RBC Transfusion Independence (RBC-TI)

    Per protocol, RBC-TI response was defined as not requiring RBC transfusion for 8 or more weeks while on treatment among participants with ≥2 units of RBC transfusions at baseline. The rate of RBC-TI was defined as the percentage of participants with ≥2 units of RBC transfusions at baseline with RBC-TI.

    Time frame: Any consecutive 8 Weeks during the study (up to approximately 5 years)

  10. Mean Change From Baseline to Week 8 in RBC Transfusion Burden (TB) in HTB Participants

    RBC TB was defined as ≥4 units or 50% reduction during rolling 8 weeks among HTB participants. The rolling 8-week was defined as any consecutive 8 weeks during the study. HTB participants are those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Mean change from baseline to Week 8 in reduction in RBC TD in HTB participants was reported.

    Time frame: Baseline and up to 5 years

  11. Mean Change From Baseline to Week 8 in Hemoglobin Levels ≥1.5 Grams/dL in LTB Participants

    Baseline hemoglobin levels were the documented pre-transfusion hemoglobin values during the 12 weeks prior to treatment. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Mean change from baseline to Week 8 in hemoglobin levels ≥1.5 grams/dL in LTB participants were reported.

    Time frame: Baseline and Week 8

  12. Serum Concentration of Luspatercept

    Blood samples were collected at pre-determined time points to determine the serum concentration of luspatercept. Serum concentrations that were below the limit of quantitation (LOQ) of the assay prior to the first dose were assigned a numerical value of zero. Post-treatment serum concentrations that were below the LOQ of the assay were treated as missing. Serum concentrations assigned a value of missing were omitted from the analysis. The LOQ of the assay was 50 ng/mL.

    Time frame: Day 1: Cycles 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 (each cycle length = 21 days); End of treatment (EOT) Day 1853

  13. Percent Change From Baseline to Day 1853 in Concentration of Serum Iron

    Blood samples were collected at pre-specified time intervals to determine serum iron concentration. The percentage change from baseline to Day 1853 in concentration of serum iron was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  14. Percent Change From Baseline to Day 1853 in Total Iron Binding Capacity (TIBC)

    Blood samples were collected at pre-specified time intervals to determine TIBC. The percentage change from baseline to Day 1853 in TIBC was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  15. Percent Change From Baseline to Day 1853 in Concentration of Transferrin

    Blood samples were collected at pre-specified time intervals to determine serum transferrin concentration. The percentage change from baseline to Day 1853 in concentration of transferrin was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  16. Percent Change From Baseline to Day 1853 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 to Day 1853 in concentration of soluble transferrin receptor was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  17. Percent Change From Baseline to Day 1853 in Concentration of Serum Ferritin

    Blood samples were collected at pre-specified time intervals to determine serum ferritin concentration. The percentage change from baseline to Day 1853 in concentration of serum ferritin was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  18. Percent Change From Baseline to Day 1853 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 1853

  19. Percent Change From Baseline to Day 1853 in Concentration of Serum Hepcidin

    Blood samples were to be collected at pre-specified time intervals to determine concentration of serum hepcidin. 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 1853

  20. Percent Change From Baseline to Day 1853 in Concentration of Serum Erythropoietin

    Blood samples were collected at pre-specified time intervals to determine serum erythropoietin concentration. The percentage change from baseline to Day 1853 in concentration of serum erythropoietin was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  21. Percent Change From Baseline to Day 1853 in Reticulocyte Count

    Blood samples were collected at pre-specified time intervals to determine reticulocyte count. The percentage change from baseline to Day 1853 in reticulocyte count was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  22. Percent Change From Baseline to Day 1853 in Nucleated RBC (nRBC) Count

    Blood samples were to be collected at pre-specified time intervals to determine 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 1853

  23. Percent Change From Baseline to Day 1853 in Direct Bilirubin Level

    Blood samples were collected at pre-specified time intervals to determine serum direct bilirubin concentration. The percentage change from baseline to Day 1853 in concentration of direct bilirubin was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  24. Percent Change From Baseline to Day 1853 in Total Bilirubin Level

    Blood samples were collected at pre-specified time intervals to determine total bilirubin concentration. The percentage change from baseline to Day 1853 in concentration of total bilirubin was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  25. Percent Change From Baseline to Day 1853 in Lactate Dehydrogenase Level

    Blood samples were collected at pre-specified time intervals to determine serum lactate dehydrogenase level. The percentage change from baseline to Day 1853 in concentration of lactate dehydrogenase level was reported.

    Time frame: Baseline (prior to first dose of luspatercept) and Day 1853

  26. Percent Change From Baseline to Day 1853 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP)

    Blood samples were to be collected at pre-specified time intervals to determine BSAP. 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 1853

  27. Percent Change From Baseline to Day 1853 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX)

    Blood samples were to be collected at pre-specified time intervals to determine CTX. 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 1853

07

Results

Posted Jul 29, 2024

Participant flow

Participant flow — Overall Study
MilestoneLuspatercept Extension Population
Started75
Completed14
Not completed61
Withdrew: Death12
Withdrew: Lost to follow-up2
Withdrew: Withdrawal by subject9
Withdrew: Presence of ≥1% blasts in peripheral blood1
Withdrew: Protocol deviation3
Withdrew: Sponsor decision22
Withdrew: Not reported12

Outcome measures

PrimaryNumber 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 was reported.

Time frame:
Up to approximately 5 years
Reported as:
Count of participants · Participants
Number of Participants Who Experienced an Adverse Event (AE)
ParticipantsLuspatercept Extension Population
Number of Participants Who Experienced an Adverse Event (AE)75
PrimaryNumber 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 luspatercept due to an AE was reported.

Time frame:
Up to approximately 5 years
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Study Treatment Due to an AE
ParticipantsLuspatercept Extension Population
Number of Participants Who Discontinued Study Treatment Due to an AE23
SecondaryPercentage of Participants With Modified Erythroid Response (mHI-E) Per International Working Group (IWG) 2006 Response Criteria

The mHI-E was defined as a mean hemoglobin (Hgb) increase ≥1.5 g/dL over an 8-week period as compared to baseline, not influenced by red blood cell (RBC) transfusion in low transfusion burden (LTB) participants and a decrease of ≥4 units or ≥50% of units of RBCs transfused over a period of 8 weeks, relative to the number of units of RBCs transfused in the 8 weeks immediately prior to baseline in high transfusion burden (HTB) participants. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 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 (up to approximately 5 years)
Reported as:
Number · Percentage of participants
Percentage of Participants With Modified Erythroid Response (mHI-E) Per International Working Group (IWG) 2006 Response Criteria
Percentage of participantsLuspatercept Extension Population
Percentage of Participants With Modified Erythroid Response (mHI-E) Per International Working Group (IWG) 2006 Response Criteria81.3 (70.7 to 89.4)
SecondaryRate of Erythroid Response (HI-E) Per IWG 2006 Response Criteria

Per IWG 2006 response criteria, the rate of HI-E was defined as the percentage of participants with an HI-E response by an Hgb increase of ≥1.5 g/dL for participants not transfused or as defined by having received less than 4 units of RBCs within 8 weeks of baseline or reduction by ≥4 units of RBCs transfused (for a Hgb≤9.0 g/dL) during any 8-week period on study, compared with the 8-week period prior to study day 1.

Time frame:
Any consecutive 8 weeks during the study (up to approximately 5 years)
Reported as:
Number · Percentage of participants
Rate of Erythroid Response (HI-E) Per IWG 2006 Response Criteria
Percentage of participantsLuspatercept Extension Population
Rate of Erythroid Response (HI-E) Per IWG 2006 Response Criteria80.0 (69.2 to 88.4)
SecondaryRate of Neutrophil Response (HI-N) Per IWG 2006 Response Criteria

Per IWG 2006 response criteria, HI-N response was defined for participants with baseline absolute neutrophil count (ANC) \<1.0×10\^9/L as the percentage increase ≥100% and an absolute mean increase \>0.5 ×10\^9/L during any rolling 8-week window on treatment compared with baseline. The rolling 8-week was defined as any consecutive 8 weeks during the study. Percentage of participants with HI-N response were reported.

Time frame:
Any consecutive 8 Weeks during the study (up to approximately 5 years)
Reported as:
Number · Percentage of participants
Rate of Neutrophil Response (HI-N) Per IWG 2006 Response Criteria
Percentage of participantsLuspatercept Extension Population
Rate of Neutrophil Response (HI-N) Per IWG 2006 Response Criteria64.3 (35.1 to 87.2)
SecondaryRate of Platelet Response (HI-P) Per IWG 2006 Response Criteria

Per IWG 2006 response criteria, HI-P response was defined for participants with baseline platelet count \<100×10\^9/L as the following: 1) For participants with baseline ≥20×10\^9/L, an absolute increase of ≥30×10\^9/L during any rolling 8-week window on treatment and 2) For participants with baseline \<20×10\^9/L, mean value of \>20×10\^9/L and percentage increase ≥100% during any rolling 8-week window on treatment. The rolling 8-week was defined as any consecutive 8 weeks during the study. Percentage of participants with HI-P response were reported.

Time frame:
Any consecutive 8 Weeks during the study (up to approximately 5 years)
Reported as:
Number · Percentage of participants
Rate of Platelet Response (HI-P) Per IWG 2006 Response Criteria
Percentage of participantsLuspatercept Extension Population
Rate of Platelet Response (HI-P) Per IWG 2006 Response Criteria36.4 (10.9 to 69.2)
SecondaryDuration of HI-E in LTB Participants Per IWG 2006 Response Criteria

For LTB participants, HI-E was defined as all Hgb increase ≥1.5 g/dL during any rolling 8 weeks window. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Per IWG 2006 response criteria, duration of HI-E was defined as the time from the first day of the first rolling 8 weeks interval of showing response to the last day of the last consecutive rolling 8 weeks interval of showing response. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

Time frame:
up to approximately 5 years
Reported as:
Mean · Days
Duration of HI-E in LTB Participants Per IWG 2006 Response Criteria
DaysLuspatercept Extension Population
Duration of HI-E in LTB Participants Per IWG 2006 Response Criteria299 ± 378.3
SecondaryDuration of HI-E in HTB Participants Per IWG 2006 Response Criteria

For HTB participants, HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Per IWG 2006 response criteria, duration of HI-E was defined as the time from the first day of the first rolling 8 weeks interval of showing response to the last day of the last consecutive rolling 8 weeks interval of showing response. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

Time frame:
up to approximately 5 years
Reported as:
Mean · Days
Duration of HI-E in HTB Participants Per IWG 2006 Response Criteria
DaysLuspatercept Extension Population
Duration of HI-E in HTB Participants Per IWG 2006 Response Criteria328 ± 286.8
SecondaryTime to HI-E in LTB Participants Per IWG 2006 Response Criteria

For LTB participants, HI-E was defined as all Hgb increase ≥1.5 g/dL during any rolling 8 weeks window. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Per IWG 2006 response criteria, time to HI-E was defined as the first date of the rolling 8 weeks interval of showing response minus first dose date plus 1. Rolling 8 weeks was defined as any consecutive 8 weeks during the study. When there were multiple disjointed intervals with response, the longest interval was used.

Time frame:
up to approximately 5 years
Reported as:
Mean · Days
Time to HI-E in LTB Participants Per IWG 2006 Response Criteria
DaysLuspatercept Extension Population
Time to HI-E in LTB Participants Per IWG 2006 Response Criteria83 ± 86.2
SecondaryTime to HI-E in HTB Participants Per IWG 2006 Response Criteria

For HTB participants, HI-E was defined as RBC transfusion reduction ≥4 units during any rolling 8 weeks. HTB participants were those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Per IWG 2006 response criteria, time to HI-E was defined as the first date of the rolling 8 weeks interval of showing response minus first dose date plus 1. Rolling 8 weeks was defined as any consecutive 8 weeks during the study.

Time frame:
Any consecutive 8 weeks during the study (up to approximately 5 years)
Reported as:
Mean · Days
Time to HI-E in HTB Participants Per IWG 2006 Response Criteria
DaysLuspatercept Extension Population
Time to HI-E in HTB Participants Per IWG 2006 Response Criteria13 ± 22.6
SecondaryRate of RBC Transfusion Independence (RBC-TI)

Per protocol, RBC-TI response was defined as not requiring RBC transfusion for 8 or more weeks while on treatment among participants with ≥2 units of RBC transfusions at baseline. The rate of RBC-TI was defined as the percentage of participants with ≥2 units of RBC transfusions at baseline with RBC-TI.

Time frame:
Any consecutive 8 Weeks during the study (up to approximately 5 years)
Reported as:
Number · Percentage of participants
Rate of RBC Transfusion Independence (RBC-TI)
Percentage of participantsLuspatercept Extension Population
Rate of RBC Transfusion Independence (RBC-TI)64.3 (48.0 to 78.4)
SecondaryMean Change From Baseline to Week 8 in RBC Transfusion Burden (TB) in HTB Participants

RBC TB was defined as ≥4 units or 50% reduction during rolling 8 weeks among HTB participants. The rolling 8-week was defined as any consecutive 8 weeks during the study. HTB participants are those who required a transfusion of ≥4 units of RBCs in the 8 weeks prior to baseline. Mean change from baseline to Week 8 in reduction in RBC TD in HTB participants was reported.

Time frame:
Baseline and up to 5 years
Reported as:
Mean · Units of blood
Mean Change From Baseline to Week 8 in RBC Transfusion Burden (TB) in HTB Participants
Units of bloodLuspatercept Extension Population
Mean Change From Baseline to Week 8 in RBC Transfusion Burden (TB) in HTB Participants-4.4 ± 2.6
SecondaryMean Change From Baseline to Week 8 in Hemoglobin Levels ≥1.5 Grams/dL in LTB Participants

Baseline hemoglobin levels were the documented pre-transfusion hemoglobin values during the 12 weeks prior to treatment. LTB participants were those who received \<4 units of RBCs within 8 weeks prior to baseline. Mean change from baseline to Week 8 in hemoglobin levels ≥1.5 grams/dL in LTB participants were reported.

Time frame:
Baseline and Week 8
Reported as:
Mean · grams/dl
Mean Change From Baseline to Week 8 in Hemoglobin Levels ≥1.5 Grams/dL in LTB Participants
grams/dlLuspatercept Extension Population
Mean Change From Baseline to Week 8 in Hemoglobin Levels ≥1.5 Grams/dL in LTB Participants2.4 ± 1.0
SecondarySerum Concentration of Luspatercept

Blood samples were collected at pre-determined time points to determine the serum concentration of luspatercept. Serum concentrations that were below the limit of quantitation (LOQ) of the assay prior to the first dose were assigned a numerical value of zero. Post-treatment serum concentrations that were below the LOQ of the assay were treated as missing. Serum concentrations assigned a value of missing were omitted from the analysis. The LOQ of the assay was 50 ng/mL.

Time frame:
Day 1: Cycles 1, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73, 77, and 81 (each cycle length = 21 days); End of treatment (EOT) Day 1853
Reported as:
Mean · µg/mL
Serum Concentration of Luspatercept
µg/mLLuspatercept Extension Population
Cycle 1 Day 10.509 ± 0.738
Cycle 5 Day 16.373 ± 3.527
Cycle 9 Day 16.589 ± 4.32
Cycle 13 Day 17.154 ± 4.423
Cycle 17 Day 18.136 ± 4.476
Cycle 21 Day 18.227 ± 3.811
Cycle 25 Day 17.986 ± 4.061
Cycle 29 Day 18.379 ± 2.884
Cycle 33 Day 18.024 ± 3.035
Cycle 37 Day 18.017 ± 3.724
Cycle 41 Day 17.559 ± 3.582
Cycle 45 Day 18.614 ± 4.015
Cycle 49 Day 19.447 ± 2.967
Cycle 53 Day 17.936 ± 2.982
Cycle 57 Day 18.891 ± 3.053
Cycle 61 Day 18.288 ± 3.753
Cycle 65 Day 18.698 ± 4.729
Cycle 69 Day 17.603 ± 3.144
Cycle 73 Day 18.559 ± 3.68
Cycle 77 Day 17.539 ± 2.555
Cycle 81 Day 19.837 ± NA
EOT (Day 1853)6.732 ± 4.356
SecondaryPercent Change From Baseline to Day 1853 in Concentration of Serum Iron

Blood samples were collected at pre-specified time intervals to determine serum iron concentration. The percentage change from baseline to Day 1853 in concentration of serum iron was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Concentration of Serum Iron
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Concentration of Serum Iron20.38 ± 70.489
SecondaryPercent Change From Baseline to Day 1853 in Total Iron Binding Capacity (TIBC)

Blood samples were collected at pre-specified time intervals to determine TIBC. The percentage change from baseline to Day 1853 in TIBC was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Total Iron Binding Capacity (TIBC)
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Total Iron Binding Capacity (TIBC)-11.37 ± 11.979
SecondaryPercent Change From Baseline to Day 1853 in Concentration of Transferrin

Blood samples were collected at pre-specified time intervals to determine serum transferrin concentration. The percentage change from baseline to Day 1853 in concentration of transferrin was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Concentration of Transferrin
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Concentration of Transferrin-11.34 ± 11.587
SecondaryPercent Change From Baseline to Day 1853 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 to Day 1853 in concentration of soluble transferrin receptor was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Concentration of Soluble Transferrin Receptor
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Concentration of Soluble Transferrin Receptor11.52 ± 48.541
SecondaryPercent Change From Baseline to Day 1853 in Concentration of Serum Ferritin

Blood samples were collected at pre-specified time intervals to determine serum ferritin concentration. The percentage change from baseline to Day 1853 in concentration of serum ferritin was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Concentration of Serum Ferritin
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Concentration of Serum Ferritin71.61 ± 152.948
SecondaryPercent Change From Baseline to Day 1853 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 1853

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 1853 in Concentration of Serum Hepcidin

Blood samples were to be collected at pre-specified time intervals to determine concentration of serum hepcidin. 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 1853

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 1853 in Concentration of Serum Erythropoietin

Blood samples were collected at pre-specified time intervals to determine serum erythropoietin concentration. The percentage change from baseline to Day 1853 in concentration of serum erythropoietin was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Concentration of Serum Erythropoietin
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Concentration of Serum Erythropoietin2252.15 ± 14490.300
SecondaryPercent Change From Baseline to Day 1853 in Reticulocyte Count

Blood samples were collected at pre-specified time intervals to determine reticulocyte count. The percentage change from baseline to Day 1853 in reticulocyte count was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Reticulocyte Count
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Reticulocyte Count78.70 ± 137.168
SecondaryPercent Change From Baseline to Day 1853 in Nucleated RBC (nRBC) Count

Blood samples were to be collected at pre-specified time intervals to determine 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 1853

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 1853 in Direct Bilirubin Level

Blood samples were collected at pre-specified time intervals to determine serum direct bilirubin concentration. The percentage change from baseline to Day 1853 in concentration of direct bilirubin was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Direct Bilirubin Level
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Direct Bilirubin Level110.53 ± 572.494
SecondaryPercent Change From Baseline to Day 1853 in Total Bilirubin Level

Blood samples were collected at pre-specified time intervals to determine total bilirubin concentration. The percentage change from baseline to Day 1853 in concentration of total bilirubin was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Total Bilirubin Level
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Total Bilirubin Level72.17 ± 236.953
SecondaryPercent Change From Baseline to Day 1853 in Lactate Dehydrogenase Level

Blood samples were collected at pre-specified time intervals to determine serum lactate dehydrogenase level. The percentage change from baseline to Day 1853 in concentration of lactate dehydrogenase level was reported.

Time frame:
Baseline (prior to first dose of luspatercept) and Day 1853
Reported as:
Mean · Percent change
Percent Change From Baseline to Day 1853 in Lactate Dehydrogenase Level
Percent changeLuspatercept Extension Population
Percent Change From Baseline to Day 1853 in Lactate Dehydrogenase Level22.98 ± 43.017
SecondaryPercent Change From Baseline to Day 1853 in Concentration of Serum Bone-Specific Alkaline Phosphatase (BSAP)

Blood samples were to be collected at pre-specified time intervals to determine BSAP. 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 1853

No measurements were reported for this outcome.

SecondaryPercent Change From Baseline to Day 1853 in Concentration of Serum Cross-Linked C-Telopeptide of Type I Collagen (CTX)

Blood samples were to be collected at pre-specified time intervals to determine CTX. 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 1853

No measurements were reported for this outcome.

Adverse events

Collected over up to approximately 5 years. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Luspatercept 0.5 mg/kg0/1 (0%)1/1 (100%)0/1 (0%)
Luspatercept 0.75 mg/kg0/2 (0%)1/2 (50%)1/2 (50%)
Luspatercept 1 mg/kg4/73 (5.5%)19/73 (26%)44/73 (60.3%)
Luspatercept 1.33 mg/kg3/61 (4.9%)16/61 (26.2%)29/61 (47.5%)
Luspatercept 1.75 mg/kg6/49 (12.2%)34/49 (69.4%)38/49 (77.6%)
Most frequent serious events
Showing 10 of 88
Most frequent serious events
EventLuspatercept 0.5 mg/kgLuspatercept 0.75 mg/kgLuspatercept 1 mg/kgLuspatercept 1.33 mg/kgLuspatercept 1.75 mg/kg
Sudden deathGeneral disorders1/10/20/730/610/49
Myelodysplastic syndromeNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/11/20/730/613/49
ErysipelasInfections and infestations0/10/20/730/614/49
SepsisInfections and infestations0/10/20/730/614/49
PneumoniaInfections and infestations0/10/22/732/613/49
Femur fractureInjury, poisoning and procedural complications0/10/20/730/613/49
Transformation to acute myeloid leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/10/21/733/611/49
SyncopeNervous system disorders0/10/23/731/610/49
Cardiac failureCardiac disorders0/10/22/730/612/49
Cardiac failure chronicCardiac disorders0/10/20/730/612/49
Most frequent other events
Showing 10 of 49
Most frequent other events
EventLuspatercept 0.5 mg/kgLuspatercept 0.75 mg/kgLuspatercept 1 mg/kgLuspatercept 1.33 mg/kgLuspatercept 1.75 mg/kg
ThrombocytopeniaBlood and lymphatic system disorders0/11/21/731/614/49
ToothacheGastrointestinal disorders0/11/21/731/611/49
FatigueGeneral disorders0/11/28/732/616/49
Urinary tract infectionInfections and infestations0/11/24/731/6110/49
ArthralgiaMusculoskeletal and connective tissue disorders0/11/23/733/614/49
DizzinessNervous system disorders0/11/23/732/613/49
EpistaxisRespiratory, thoracic and mediastinal disorders0/11/25/732/613/49
NeutropeniaBlood and lymphatic system disorders0/11/20/730/610/49
Macular degenerationEye disorders0/11/20/730/610/49
Mucosal inflammationGeneral disorders0/11/21/730/610/49

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Luspatercept Extension Population
Mean70.9 ± 11.0
Sex: Female, Male
Sex: Female, Male(Participants)Luspatercept Extension Population
Female25
Male50
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Luspatercept Extension Population
Hispanic or Latino0
Not Hispanic or Latino67
Unknown or Not Reported8
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Luspatercept Extension Population
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White75
More than one race0
Unknown or Not Reported0
Transfusion Status
Transfusion Status(Participants)Luspatercept Extension Population
HTB25
LTB50
Hemoglobin level
Hemoglobin level(grams/dl)Luspatercept Extension Population
Mean8.74 ± 1.01
08

Study locations

1 site
  • Acceleron Investigative Site
    Dresden, Germany
09

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. PubMed 28870615 ↗

Study documents

  • Study protocol · Mar 29, 2019
  • Statistical analysis plan · May 8, 2020

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

Data sharing details ↗ · engagezone.msd.com

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Oct 2014 to primary completion in Mar 2020, 65 months.

Results were first posted in Jul 2024, 4 years 4 months after primary completion.

Of 52 industry-sponsored phase 2 interventional studies under Myelodysplastic Syndromes, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 30 and three quarters within 59. This study's 65 months is above that.

Counting every sponsor, half of 305 studies reached it within 64 months; a quarter within 39 and three quarters within 104.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 6, 2014
First posted
Oct 20, 2014
StartActual
Oct 9, 2014
Primary completionActual
Mar 19, 2020
CompletionActual
Mar 19, 2020
Results first posted
Jul 29, 2024
Last update
Jul 29, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
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 ↗
11

Registry details

Key details

Study ID
NCT02268383
Lead sponsor
Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA
Responsible party
Sponsor
First posted
Oct 20, 2014
Start date
Oct 9, 2014
Primary completion
Mar 19, 2020
Completion
Mar 19, 2020
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 ↗

Not currently enrolling

This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Luspatercept

Other studies in this condition

Myelodysplastic Syndromes →

Other studies from this sponsor

Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA →

Start the discussion