Summary

Eligibility
for males ages 4 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around
Principal Investigator
by Perry Shieh (ucla)

Description

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.

Official Title

A PHASE 1B MULTICENTER, OPEN-LABEL, SINGLE ASCENDING DOSE STUDY TO EVALUATE THE SAFETY AND TOLERABILITY OF PF-06939926 IN AMBULATORY AND NON-AMBULATORY SUBJECTS WITH DUCHENNE MUSCULAR DYSTROPHY

Keywords

Duchenne Muscular Dystrophy, gene therapy, mini-dystrophin, AAV, fordadistrogene movaparvovec, Muscular Dystrophies

Eligibility

You can join if…

Open to males ages 4 years and up

  • Age as follows, based on ambulatory status:
    • FOR AMBULATORY PARTICIPANTS, defined as the ability to walk at least 10 meters unassisted: Between 4 and 12 years, inclusive,
    • FOR NON-AMBULATORY PARTICIPANTS, defined as the inability to walk at least 10 meters unassisted: 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 to these procedures;
  • Ability to tolerate muscle biopsies under anesthesia with no contraindications to these procedures;
  • 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, but which may be managed or adjusted to a lower limit, especially to ensure participant safety;
  • 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.

You CAN'T join if...

  • 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, as follows, 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.
  • The following genetic abnormalities in the dystrophin gene as confirmed by the investigator based on the review of the DMD genetic testing:
    1. Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR
    2. A deletion that affects both exon 29 and exon 30.

      Sirolimus Cohort

      Inclusion Criteria

  • > 8 years of age Exclusion Criteria
  • Hypersensitivity to sirolimus or intolerance to soy, including a history of angioedema
  • Concomitant use with strong CYP3A4/P-gp inducers or inhibitors

Locations

  • MRI Research Center
    Los Angeles California 90095 United States
  • Reed Neurological Research Center
    Los Angeles California 90095 United States
  • Ronald Reagan UCLA Medical Center (Investigational Drug Section)
    Los Angeles California 90095 United States
  • Ronald Reagan UCLA Medical Center Drug Information Center
    Los Angeles California 90095 United States
  • UCLA (David Geffen School of Medicine)
    Los Angeles California 90095 United States
  • UCLA Mattel Children's Hospital
    Los Angeles California 90095 United States
  • UCLA Medical Center
    Los Angeles California 90095 United States
  • UCLA Outpatient Surgery Center
    Los Angeles California 90095 United States

Lead Scientist at University of California Health

  • Perry Shieh (ucla)
    HS Clinical Professor, Neurology, Medicine. Authored (or co-authored) 87 research publications

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Pfizer
Links
To obtain contact information for a study center near you, click here.
ID
NCT03362502
Phase
Phase 1 Duchenne Muscular Dystrophy Research Study
Study Type
Interventional
Participants
About 23 people participating
Last Updated