A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes
Summary
The study will be conducted in compliance with the International Council on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good Clinical Practice (GCP) and applicable regulatory requirements. This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) versus placebo in participants with anemia due to the Revised International Prognostic Scoring System (IPSS-R) very low, low, or intermediate MDS with ring sideroblasts who require red blood cell (RBC) transfusions.
Timeline
- Start
- 2016-02-09
- Primary completion
- 2019-06-18
- Completion
- 2020-11-26
Outcome
Met primary endpoint
registry analysis (superiority test); Luspatercept vs Placebo; p <0.0001; Common Risk Difference on Response Rate 24.56 (95% CI 14.48 to 34.64); Cochran-Mantel-Haenszel NCT02631070 ↗
paper 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). PMID 31914241 ↗
release “MEDALIST achieved a statistically significant improvement in the primary endpoint of red blood cell transfusion independence” bms.com ↗
Publications
- Background Porter J. Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):361-370. doi: 10.1182/asheducation-2018.1.361.
- Background Piga A, Perrotta S, Gamberini MR, Voskaridou E, Melpignano A, Filosa A, Caruso V, Pietrangelo A, Longo F, Tartaglione I, Borgna-Pignatti C, Zhang X, Laadem A, Sherman ML, Attie KM. Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with beta-thalassemia. Blood. 2019 Mar 21;133(12):1279-1289. doi: 10.1182/blood-2018-10-879247. Epub 2019 Jan 7.
- Results Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, Diez-Campelo M, Finelli C, Cazzola M, Ilhan O, Sekeres MA, Falantes JF, Arrizabalaga B, Salvi F, Giai V, Vyas P, Bowen D, Selleslag D, DeZern AE, Jurcic JG, Germing U, Gotze KS, Quesnel B, Beyne-Rauzy O, Cluzeau T, Voso MT, Mazure D, Vellenga E, Greenberg PL, Hellstrom-Lindberg E, Zeidan AM, Ades L, Verma A, Savona MR, Laadem A, Benzohra A, Zhang J, Rampersad A, Dunshee DR, Linde PG, Sherman ML, Komrokji RS, List AF. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. N Engl J Med. 2020 Jan 9;382(2):140-151. doi: 10.1056/NEJMoa1908892.
- Results Komrokji RS. Luspatercept in Myelodysplastic Syndromes: Who and When? Hematol Oncol Clin North Am. 2020 Apr;34(2):393-400. doi: 10.1016/j.hoc.2019.10.004. Epub 2020 Jan 21.
- Results Fenaux P, Kiladjian JJ, Platzbecker U. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood. 2019 Feb 21;133(8):790-794. doi: 10.1182/blood-2018-11-876888. Epub 2019 Jan 2.
- Germing U, Fenaux P, Platzbecker U, Buckstein R, Santini V, Diez-Campelo M, Yucel A, Tang D, Fabre S, Zhang G, Zoffoli R, Ha X, Miteva D, Hughes C, Komrokji RS, Zeidan AM, Garcia-Manero G. Improved benefit of continuing luspatercept therapy: sub-analysis of patients with lower-risk MDS in the MEDALIST study. Ann Hematol. 2023 Feb;102(2):311-321. doi: 10.1007/s00277-022-05071-8. Epub 2023 Jan 13.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Luspatercept | Protein / enzyme biologic | 1 mg/kg | Subcutaneous |
| Subject | Luspatercept | Protein / enzyme biologic | 1.75 mg/kg | Subcutaneous |