A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of PF-06252616 in Duchenne Muscular Dystrophy
Summary
This is a Phase 2 randomized, 2-period, double-blind, placebo-controlled, multiple ascending dose study to evaluate the safety, efficacy, PK and PD of PF-06252616 administered to ambulatory boys diagnosed with Duchenne Muscular Dystrophy. Three intravenous (IV) dose levels will be investigated in a within subject dose escalating fashion. Subjects will be randomly assigned to 1 of 3 sequence groups for approximately 96 weeks (2 periods of 48 weeks each). In period 1, two of the sequence groups will receive PF-06252616 and one sequence group will receive placebo. In period 2, the placebo group will switch to PF-06252616 and the two remaining sequence groups will either receive placebo or PF-06252616. Efficacy will be based on an observed mean change from baseline on function (4 stair climb) of PF-06252616 as compared to the placebo at the end of period 1. Period 2 provides an opportunity to evaluate PK. Subjects will receive monthly IV infused doses of either PF-06252616 or placebo and will undergo safety evaluations (Laboratory, cardiac monitoring, physical exams, x-ray, MRI), functional evaluations (pulmonary function testing, 4 stair climb, range of motion, strength testing, Northstar Ambulatory Assessment, upper limb functional testing and the six minute walk test), pharmacokinetic testing and pharmacodynamic testing to evaluate changes in muscle volume (MRI).
Timeline
- Start
- 2014-11-24
- Primary completion
- 2018-04-30
- Completion
- 2018-11-23
Outcome
Missed primary endpoint
Stopped: “Termination Date 30AUG2018: Reason for termination: Lack of Efficacy”
registry analysis (superiority test); Placebo vs Domagrozumab; p = 0.2088; Mean Difference (Net) 1.293 (95% CI -0.7343 to 3.3200); NCT02310763 ↗
registry analysis (superiority test); Placebo vs Domagrozumab; p = 0.9423; Mean Difference (Net) 0.2712 (95% CI -7.3799 to 7.9223); NCT02310763 ↗
release “The Phase 2 study (B5161002), did not meet its primary efficacy endpoint” pfizer.com ↗
Publications
- Sherlock SP, McCrady A, Palmer J, Aghamolaey H, Ahlgren A, Widholm P, Dahlqvist Leinhard O, Karlsson M. Relationship Between Quantitative Magnetic Resonance Imaging Measures and Functional Changes in Patients With Duchenne Muscular Dystrophy. Muscle Nerve. 2025 Mar;71(3):343-352. doi: 10.1002/mus.28321. Epub 2024 Dec 23.
- Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Tian C, Mah JK, Muntoni F, Guglieri M, Butterfield RJ, Charnas L, Marraffino S. Dual-energy X-ray absorptiometry measures of lean body mass as a biomarker for progression in boys with Duchenne muscular dystrophy. Sci Rep. 2022 Nov 5;12(1):18762. doi: 10.1038/s41598-022-23072-5.
- Wojciechowski J, Purohit VS, Harnisch LO, Dua P, Tan B, Nicholas T. Population PK and PD Analysis of Domagrozumab in Pediatric Patients with Duchenne Muscular Dystrophy. Clin Pharmacol Ther. 2022 Dec;112(6):1291-1302. doi: 10.1002/cpt.2747. Epub 2022 Oct 4.
- Muntoni F, Guglieri M, Mah JK, Wagner KR, Brandsema JF, Butterfield RJ, McDonald CM, Mayhew AG, Palmer JP, Marraffino S, Charnas L, Mercuri E. Novel approaches to analysis of the North Star Ambulatory Assessment (NSAA) in Duchenne muscular dystrophy (DMD): Observations from a phase 2 trial. PLoS One. 2022 Aug 23;17(8):e0272858. doi: 10.1371/journal.pone.0272858. eCollection 2022.
- Sherlock SP, Palmer J, Wagner KR, Abdel-Hamid HZ, Bertini E, Tian C, Mah JK, Kostera-Pruszczyk A, Muntoni F, Guglieri M, Brandsema JF, Mercuri E, Butterfield RJ, McDonald CM, Charnas L, Marraffino S. Quantitative magnetic resonance imaging measures as biomarkers of disease progression in boys with Duchenne muscular dystrophy: a phase 2 trial of domagrozumab. J Neurol. 2022 Aug;269(8):4421-4435. doi: 10.1007/s00415-022-11084-0. Epub 2022 Apr 8.
- Wagner KR, Guglieri M, Ramaiah SK, Charnas L, Marraffino S, Binks M, Vaidya VS, Palmer J, Goldstein R, Muntoni F. Safety and disease monitoring biomarkers in Duchenne muscular dystrophy: results from a Phase II trial. Biomark Med. 2021 Oct;15(15):1389-1396. doi: 10.2217/bmm-2021-0222. Epub 2021 Sep 17.
- Sherlock SP, Zhang Y, Binks M, Marraffino S. Quantitative muscle MRI biomarkers in Duchenne muscular dystrophy: cross-sectional correlations with age and functional tests. Biomark Med. 2021 Jun;15(10):761-773. doi: 10.2217/bmm-2020-0801. Epub 2021 Jun 22.
- Wagner KR, Abdel-Hamid HZ, Mah JK, Campbell C, Guglieri M, Muntoni F, Takeshima Y, McDonald CM, Kostera-Pruszczyk A, Karachunski P, Butterfield RJ, Mercuri E, Fiorillo C, Bertini ES, Tian C, Statland J, Sadosky AB, Purohit VS, Sherlock SP, Palmer JP, Binks M, Charnas L, Marraffino S, Wong BL. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jun;30(6):492-502. doi: 10.1016/j.nmd.2020.05.002. Epub 2020 May 19.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | domagrozumab | Monoclonal antibody | 5 mg/kg | Intravenous |
| Subject | domagrozumab | Monoclonal antibody | 20 mg/kg | Intravenous |
| Subject | domagrozumab | Monoclonal antibody | 40 mg/kg | Intravenous |