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).
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/Exclusion criteria apply.
Primary outcome:
1. 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 (Time Frame - Up to Week 96):
TD is defined as ≥ 3 red blood cells (RBC) units/16 weeks assessed by International
Working Group (IWG) 2018.
Secondary outcome:
1. 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 (Time Frame - Up to Week 48)
2. 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 (Time Frame - Up to Week 48)
3. 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 (Time Frame - From Week 49 to Week 96)
4. 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 (Time Frame - Up to Week 96)
5. 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 (Time Frame - Up to Week 48)
6. 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 (Time Frame - From Week 49 to Week 96)
7. 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 (Time Frame - Up to Week 96)
8. Mean Hb change over fixed 24-week periods compared to the baseline Hb (Time Frame - Baseline, Week 24, Week 48, Week 72, Week 96)
9. 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 (Time Frame - Up to Week 96)
10. Number of participants with TD by week 48 (Time Frame - Up to Week 48)
11. Time to TD (IWG 2018 defined as ≥ 3 RBC units/16 weeks) during any continuous 16-week interval until the end of study (Time Frame - Up to 5 years)
12. Time from first Luspatercept dose to first RBC transfusion (Time Frame - Up to 5 years)
13. Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within 48-week treatment period in absence of transfusion (Time Frame - Up to Week 48)
14. Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within 96-week treatment period in absence of transfusion (Time Frame - Up to Week 96)
15. 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 Treatment Period in the absence of transfusion) (Time Frame - Up to Week 48)
16. 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 96-week Treatment Period in the absence of transfusion) (Time Frame - Up to Week 96)
17. Number of participants with RBC transfusion independence over at least a consecutive 24-week period (Time Frame - Up to 5 years)
18. Number of transfusions (Time Frame - Up to 5 years)
19. Number of transfusions visits/units (Time Frame - Up to 5 years)
20. 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) (Time Frame - Baseline, Up to 5 years)
21. Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L) (Time Frame - Baseline, Up to 5 years)
22. Number of participants with adverse events (AEs) (Time Frame - Up to Week 102)
23. Number of participants with antidrug antibody (ADA) (positive or negative) (Time Frame - Up to Week 102)
24. Pharmacokinetics (PK): Serum concentration (Time Frame - Up to Week 96)
25. PK: Area under the plasma concentration time curve (AUC) (Time Frame - Up to Week 96)
26. Number of participants with a platelet response at Week 24, Week 48 and Week 96 (Time Frame - 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.
27. Number of participants with a neutrophil response at Week 24, Week 48 and Week 96 (Time Frame - 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.
28. Number of participants with acute myeloid leukemia (AML) progression (Time Frame - Up to 5 years)
29. Time to AML progression (Time Frame - Up to 5 years)
30. Number of participants with high risk myelodysplastic syndromes (MDS) progression (Time Frame - Up to 5 years)
31. Time to high-risk MDS progression (Time Frame - Up to 5 years)
32. Time from date of randomization up to death due to any cause (Time Frame - Up to 5 years)
- Experimental: Luspatercept
- Active Comparator: Epoetin Alfa
- Luspatercept (BMS-986346 / ACE-536 / Reblozyl® / ):
Specified dose on specified days - Epoetin Alfa (Epogen® / PROCRIT® / BINOCRIT / ):
Specified dose on specified days
Quelle: ClinicalTrials.gov
