Myelodysplastic Syndromes
Conditions
Keywords
Luspatercept, BMS-986346, ACE-536, Myelodysplastic Syndrome, Epoetin alfa, Erythropoietin stimulating agent (ESA), Myelodysplastic Syndromes (MDS), Anaemia
Brief summary
The purpose of the study is to compare the efficacy and safety of Luspatercept vs epoetin alfa in the treatment of anemia in adults due to IPSS-R very low, low, intermediate-risk MDS in ESA-naïve participants who are non-transfusion dependent (NTD).
Interventions
BIOLOGICALLuspatercept
Specified dose on specified days
BIOLOGICALEpoetin Alfa
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has documented diagnosis of MDS according to World Health Organization (WHO) 2016 that meet IPSS-R classification of very low, low, or intermediate-risk disease, (intermediate-risk of ≤ 3.5 IPSS-R score) confirmed via bone marrow aspirate and:. i) \< 5% blasts in bone marrow and \< 1% blasts in peripheral blood. * Participant is not transfusion dependent (NTD) based on IWG2018 criteria. * Participant is erythropoiesis-stimulating agent naive. Participants may be randomized at the investigator's discretion if the participant received no more than 2 prior doses of epoetin alfa, epoetin alfa biosimilar, or darbepoetin alfa, with the last dose at least 8 weeks prior to randomization. * Participant has a baseline endogenous serum erythropoietin (sEPO) level of ≤ 500 U/L. * Participant has symptoms of anemia:. i) Participant records a severity score of "moderate" or greater on at least 1 PGI-S item of fatigue, weakness, shortness of breath, or dizziness performed during the screening period. * Participant has a baseline Hb concentration prior to randomization of ≤ 9.5 g/dL. The baseline Hb will be calculated using the mean of the two lowest available Hb measurements within 16 weeks prior to randomization and must include at least one central lab Hb reading done within the screening period (no more than 35 days before randomization). The two Hb measurements must have been performed at least seven days apart. Hb levels less than 21 days following RBC transfusion should not be used. Split samples for local assessments are not required.
Exclusion criteria
* Participant with secondary MDS (that is, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases). * Participant with known history of diagnosis of AML. * Participant with history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (including proximal and distal), pulmonary or arterial embolism, arterial thrombosis, or other venous thrombosis within 6 months prior to randomization. * Participant with a history of pure red cell aplasia and/or antibody against erythropoietin. * Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with lower-risk non-transfusion dependent myelodysplastic syndromes (NTD-MDS) who converted to Transfusion Dependence (TD) during any continuous 16-week interval within the 96-week treatment period | Up to Week 96 | TD is defined as ≥ 3 red blood cells (RBC) units/16 weeks assessed by International Working Group (IWG) 2018. |
| Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 grams/deciliter (g/dL) in any continuous 16-week interval within the 48 week Treatment Period in the absence of transfusion | Up to Week 48 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion | Up to Week 96 | — |
| Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion | Up to Week 96 | — |
| Mean Hb change over fixed 24-week periods compared to the baseline Hb | Week 24, Week 48, Week 72, Week 96 | — |
| Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 96-week treatment period in the absence of transfusion | Up to Week 96 | — |
| Number of participants with TD by week 48 | Up to Week 48 | — |
| Time to TD (IWG 2018 defined as ≥ 3 RBC units/16 weeks) during any continuous 16-week interval until the end of study | Up to 5 years | — |
| Time from first Luspatercept dose to first RBC transfusion | Up to 5 years | — |
| Duration of mHI-E in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within the 48-week and 96-week treatment period in absence of transfusion | Up to Week 96 | mHI-E: median hematologic improvement in erythroid response |
| Time from first dose to first day of response (increase in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 48-week and 96-week Treatment Period in the absence of transfusion) | Up to Week 96 | — |
| Number of participants with RBC transfusion independence over at least a consecutive 24-week period | Up to 5 years | — |
| Number of transfusions | Up to 5 years | — |
| Number of transfusions visits/units | Up to 5 years | — |
| Change from baseline in subscales of self-reported health-related quality-of-life (HRQoL) assessed by the Functional Assessment of Cancer Therapy - Anemia (FACT-An) | Up to 5 years | — |
| Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L) | Up to 5 years | — |
| Number of participants with adverse events (AEs) | Up to 42 days post last dose | — |
| Number of participants with antidrug antibody (ADA) (positive or negative) | Up to Week 96 | — |
| Pharmacokinetics (PK): Serum concentration | Up to Week 96 | — |
| PK: Area under the plasma concentration time curve (AUC) | Up to Week 96 | — |
| Number of participants with a platelet response at Week 24, Week 48 and Week 96 | Up to Week 96 | Platelet response is defined as an increase from baseline in number of platelets to ≥ 30 × 10\^9/L at Week 24, Week 48 and Week 96. |
| Number of participants with a neutrophil response at Week 24, Week 48 and Week 96 | Up to Week 96 | Neutrophil response is defined as an absolute increase from baseline of \> 0.5 × 10\^9/L neutrophils at Week 24, Week 48 and Week 96. |
| Number of participants with acute myeloid leukemia (AML) progression | Up to 5 years | — |
| Time to AML progression | Up to 5 years | — |
| Number of participants with high risk myelodysplastic syndromes (MDS) progression | Up to 5 years | — |
| Time to high-risk MDS progression | Up to 5 years | — |
| Time from date of randomization up to death due to any cause | Up to 5 years | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Czechia, France, Germany, Greece, Hungary, India, Italy, Mexico, Poland, Puerto Rico, Spain, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed