A Study to Evaluate the Safety and Tolerability of PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy

Summary

This is a first-in-human/first-in-patient, multi-center, open-label, non-randomized, ascending dose, safety and tolerability study of a single intravenous infusion of PF-06939926 in ambulatory and non-ambulatory subjects with Duchenne muscular dystrophy (DMD). Other objectives include measurement of dystrophin expression and distribution, and assessments of muscle strength, quality, and function. A total of approximately 22 subjects will receive PF-06939926, and these will include both ambulatory and non-ambulatory subjects. Up to 13 subjects may be included in a cohort that includes the concomitant medication, sirolimus. In order to mitigate unanticipated risks to subject safety, enrollment will be staggered within and between two planned dose-levels and will include a formal review by an external data monitoring committee (E-DMC) prior to dose progression.

Timeline

Start

2018-01-23

Primary completion

2022-03-28

Completion

2025-07-28

Outcome

Outcome not reported

Stopped: “All participants who have received fordadistrogene movaparvovec in any Pfizer study will now be assessed for long-term safety in 1 combined study: C3391003”

Publications

• Walsh J, Palandra J, Duriga N, Beidler D, McIntosh A, Binks M, Neubert H. Dystrophin/mini-dystrophin expression analysis by immunoaffinity liquid chromatography-tandem mass spectrometry after gene therapy for DMD. Gene Ther. 2025 Dec;32(6):573-580. doi: 10.1038/s41434-025-00554-5. Epub 2025 Aug 2.
• Byrne BJ, Butterfield RJ, Shieh PB, Smith EC, Licht C, Binks M, Casinghino S, Delnomdedieu M, Ravindra KC, McDonnell T, Ryan K, Schulz M, Shen Q, Shi H, Sirivelu MP, Vaidya VS, Whiteley L, Levy DI. Complement activation in a phase Ib study of fordadistrogene movaparvovec for Duchenne muscular dystrophy. Mol Ther. 2025 Sep 3;33(9):4226-4238. doi: 10.1016/j.ymthe.2025.06.032. Epub 2025 Jun 28.
• Sherlock SP, Levy DI, McIntosh A, Shieh PB, Smith EC, McDonnell TG, Ryan KA, Delnomdedieu M, Binks M, Lal AK, Butterfield RJ. Cardiac safety of fordadistrogene movaparvovec gene therapy in Duchenne muscular dystrophy: Initial observations from a phase 1b trial. Mol Ther. 2025 Sep 3;33(9):4216-4225. doi: 10.1016/j.ymthe.2025.06.031. Epub 2025 Jun 28.
• Butterfield RJ, Shieh PB, Li H, Binks M, McDonnell TG, Ryan KA, Delnomdedieu M, Belluscio BA, Neelakantan S, Levy DI, Schwartz PF, Smith EC. AAV mini-dystrophin gene therapy for Duchenne muscular dystrophy: a phase 1b trial. Nat Med. 2025 Aug;31(8):2712-2721. doi: 10.1038/s41591-025-03750-3. Epub 2025 Jun 27.

Drugs

Indications