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

study id #: NCT03362502

condition: Duchenne Muscular Dystrophy

status: active, not recruiting

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 30 subjects will receive PF-06939926, and these will include both ambulatory and non-ambulatory subjects. 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.

intervention: PF-06939926

mechanism of action: Gene therapy to introduce a version of dystrophin

results: https://clinicaltrials.gov/ct2/show/results/NCT03362502

last updated: October 21, 2020

start date: January 23, 2018

estimated completion: June 30, 2022

phase of development: Phase 1

size / enrollment: 30

primary outcomes:

• Incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events [ Time Frame: through 1 year post-treatment ]

secondary outcomes:

• Evidence of mini-dystrophin expression and distribution assessed by immunohistochemistry, western blot, and/or LC-MS using muscle biopsies [ Time Frame: at baseline, 2 months and 1 year post-treatment ]
  
• Incidence, severity and causal relationship of treatment-emergent adverse events [ Time Frame: through 5 years post-treatment ]
  
• Incidence and magnitude of abnormal laboratory findings [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes in physical and neurological examinations [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes in body weight [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes in vital signs [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes on electrocardiogram (ECG) [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes in body weight and vital signs [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes in cardiac MRI-measured left ventricular ejection fraction (LVEF) [ Time Frame: through 5 years post-treatment ]
  
• Incidence and severity of abnormal and clinical relevant changes in Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: through 5 years post-treatment ]

inclusion criteria:

exclusion criteria:
• Receipt of live attenuated vaccination within 3 months prior or exposure to a 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 and missense 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) or pre-existing anti-dystrophin T-cell response
• Compromised cardiac function as indicated by a left ventricular ejection fraction of less than 55% on cardiac MRI
• Inadequate hepatic or renal function or risk factors for autoimmune disease on screening laboratory assessments.

sponsor: Pfizer

• United States, California
  David Geffen School of Medicine at UCLA
  
  
• United States, California
  MRI Research Center
  
  
• United States, California
  Reed Neurological Research Center
  
  
• United States, California
  Ronald Reagan UCLA Medical Center Drug Information Center
  
  
• United States, California
  UCLA Mattel Children’s Hospital
  
  
• United States, California
  UCLA Medical Center
  
  
• United States, California
  UCLA Outpatient Surgery Center
  
  
• United States, North Carolina
  Biospecimen Repository & Processing Core
  
  
• United States, North Carolina
  Duke Cardiovascular Magnetic Resonance Center
  
  
• United States, North Carolina
  Duke Children’s Hospital
  
  
• United States, North Carolina
  Duke Early Phase Clinical Research Unit
  
  
• United States, North Carolina
  Duke Neurology
  
  
• United States, North Carolina
  Duke University Investigational Drug Services
  
  
• United States, North Carolina
  Lenox Baker Children’s Hospital at Duke University Medical Center
  
  
• United States, Utah
  CCTS Clinical Research Center
  
  
• United States, Utah
  Primary Children’s Hospital
  
  
• United States, Utah
  University of Utah Clinical Neurosciences Center
  
  
• United States, Utah
  University of Utah Hospital
  
  
• United States, Utah
  University of Utah Hospital & Clinics Investigational Drug Services
  
  
• United States, Utah
  University of Utah Imaging and Neurosciences Center