PF-06939926 Gene Therapy for Duchenne Muscular Dystrophy

Recruiting in Palo Alto (17 mi)

+24 other locations

Age: Any Age

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Pfizer

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for boys with Duchenne muscular dystrophy (DMD), both walking and non-walking, who can handle MRI scans without sedation. Participants must meet specific genetic criteria, have a certain level of muscle function, and be on stable glucocorticoids. Boys should weigh under 50 kg if walking or under 75 kg if not. Those in the Sirolimus Cohort must be over 8 years old.

Inclusion Criteria

Age as follows, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Between 4 and 12 years, FOR NON-AMBULATORY PARTICIPANTS: No age restrictions so long as loss of ambulation occurs prior to the subject's 17th birthday; Diagnosis of Duchenne muscular dystrophy confirmed by medical history and genetic testing; Receipt of glucocorticoids for 6 months and a stable daily dose for at least 3 months prior to study entry; Ability to tolerate magnetic resonance imaging (MRI) without sedation and with no contraindications; Ability to tolerate muscle biopsies under anesthesia with no contraindications; Body weights as follows, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Between 15 kg and 50 kg, FOR NON-AMBULATORY PARTICIPANTS: Less than 75 kg; Functional performance as follows, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Ability to rise from floor within seven (7) seconds, FOR NON-AMBULATORY PARTICIPANTS: Percent predicted forced vital capacity greater than 40% as part of pulmonary function tests, as well as adequate upper limb function; > 8 years of age for Sirolimus Cohort

Exclusion Criteria

Receipt of live attenuated vaccination within 3 months prior to receiving PF-06939926 or exposure to an influenza (or other inactivated) vaccination or systemic antiviral and/or interferon therapy within 30 days prior to receipt of PF-06939926; Prior exposure to any gene therapy agent, including exon-skipping agents; Exposure to other investigational drugs within 30 days or 5 half-lives, whichever is longer; Neutralizing antibodies (NAb) against adeno-associated virus, serotype 9 (AAV9); Compromised cardiac function as indicated by left ventricular ejection fraction on cardiac MRI, based on ambulatory status: FOR AMBULATORY PARTICIPANTS: Less than 55%, FOR NON-AMBULATORY PARTICIPANTS: Less than 35%; Inadequate hepatic or renal function or risk factors for autoimmune disease on screening laboratory assessments; Hypersensitivity to sirolimus or intolerance to soy, including a history of angioedema; Concomitant use with strong CYP3A4/P-gp inducers or inhibitors.

Treatment Details

Interventions

PF-06939926 (Gene Therapy)

Trial OverviewThe study tests PF-06939926 gene therapy's safety in DMD patients by giving a single IV dose to about 22 participants. It includes staggered enrollment and reviews by an external committee before increasing doses. The trial also measures dystrophin levels, muscle strength, quality, and function.

Participant Groups

1Treatment groups

Experimental Treatment

Group I: PF-06939926Experimental Treatment1 Intervention