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

• ClinicalTrials.gov Identifier: NCT03362502
• Recruitment Status: Active, not recruiting
• First Posted: December 5, 2017
• Last Update Posted: February 12, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 29, 2017
• First Posted Date: December 5, 2017
• Last Update Posted Date: February 12, 2021
• Actual Study Start Date: January 23, 2018
• Estimated Primary Completion Date: July 28, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 29, 2017): Incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events [ Time Frame: through 1 year post-treatment ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 5, 2020)

• 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 ]

Original Secondary Outcome Measures (submitted: November 29, 2017)

• Evidence of mini-dystrophin expression and distribution using upper limb muscle biopsies [ Time Frame: at baseline, 2 months and 1 year post-treatment ]
• Incidence, severity and causal relationship of treatment-emergent adverse events and clinically significant safety findings [ Time Frame: through 5 years post-treatment ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Duchenne Muscular Dystrophy

Intervention

Genetic: PF-06939926

Recombinant adeno-associated virus, serotype 9 (AAV9) carrying a truncated human dystrophin gene (mini-dystrophin) under the control of a muscle-specific promoter.

Subjects will receive a single intravenous infusion of one of 2 dose levels.

Study Arms

Experimental: PF-06939926

Intervention: Genetic: PF-06939926

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 5, 2020): 30
• Original Estimated Enrollment (submitted: November 29, 2017): 12
• Estimated Study Completion Date: July 28, 2026
• Estimated Primary Completion Date: July 28, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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.

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, 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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

• Ages: 4 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03362502
• Other Study ID Numbers: C3391001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2020