A Study to Evaluate the Safety and Tolerability of PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03362502 |
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Recruitment Status :
Active, not recruiting
First Posted : December 5, 2017
Last Update Posted : February 12, 2021
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Duchenne Muscular Dystrophy | Genetic: PF-06939926 | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 30 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | January 23, 2018 |
| Estimated Primary Completion Date : | July 28, 2022 |
| Estimated Study Completion Date : | July 28, 2026 |
| Arm | Intervention/treatment |
|---|---|
| Experimental: PF-06939926 |
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. |
- Incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events [ Time Frame: through 1 year post-treatment ]
- 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 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 4 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Gender Based Eligibility: | Yes |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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;
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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;
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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);
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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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03362502
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| Study Director: | Pfizer CT.gov Call Center | Pfizer |
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT03362502 |
| Other Study ID Numbers: |
C3391001 |
| First Posted: | December 5, 2017 Key Record Dates |
| Last Update Posted: | February 12, 2021 |
| Last Verified: | December 2020 |
| Individual Participant Data (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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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gene therapy, mini-dystrophin, AAV |
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Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases |
Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked |