Back to resultsA Study to Evaluate the Safety and Tolerability of PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy
Primary Purpose
Duchenne Muscular Dystrophy
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-06939926
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy focused on measuring gene therapy, mini-dystrophin, AAV, fordadistrogene movaparvovec
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.
The following genetic abnormalities in the dystrophin gene as confirmed by the investigator based on the review of the DMD genetic testing:
- Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR
- 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
Sites / Locations
- MRI Research Center
- Reed Neurological Research Center
- Ronald Reagan UCLA Medical Center (Investigational Drug Section)
- Ronald Reagan UCLA Medical Center Drug Information Center
- UCLA (David Geffen School of Medicine)
- UCLA Mattel Children's Hospital
- UCLA Medical Center
- UCLA Outpatient Surgery Center
- Duke Neurology
- Duke University Medical Center, Lenox Baker Children's Hospital
- Biospecimen Repository & Processing Core - BPRC
- Duke Cardiovascular Magnetic Resonance Center
- Duke Children's Hospital & Health Center
- Duke University Hospital Investigational Drug Services (IDS) Pharmacy
- CCTS Clinical Research Center
- University of Utah Imaging and Neurosciences Center
- University of Utah Hospital & Clinics Investigational Drug Services
- University of Utah Hospital
- Primary Children's Hospital
- University of Utah Clinical Neurosciences Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-06939926
Arm Description
Outcomes
Primary Outcome Measures
Incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events
Secondary Outcome Measures
Evidence of mini-dystrophin expression and distribution assessed by immunohistochemistry, western blot, and/or LC-MS using muscle biopsies
Incidence, severity and causal relationship of treatment-emergent adverse events
Incidence and magnitude of abnormal laboratory findings
Incidence and severity of abnormal and clinical relevant changes in physical and neurological examinations
Incidence and severity of abnormal and clinical relevant changes in body weight
Incidence and severity of abnormal and clinical relevant changes in vital signs
Incidence and severity of abnormal and clinical relevant changes on electrocardiogram (ECG)
Incidence and severity of abnormal and clinical relevant changes in body weight and vital signs
Incidence and severity of abnormal and clinical relevant changes in cardiac MRI-measured left ventricular ejection fraction (LVEF)
Incidence and severity of abnormal and clinical relevant changes in Columbia Suicide Severity Rating Scale (C-SSRS)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03362502
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 23, 2018 (Actual)
Primary Completion Date
March 28, 2022 (Actual)
Study Completion Date
March 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
Keywords
gene therapy, mini-dystrophin, AAV, fordadistrogene movaparvovec
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-06939926
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
PF-06939926
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of dose-limiting safety or intolerability, as measured by treatment-related adverse events
Time Frame
through 1 year post-treatment
Secondary Outcome Measure Information:
Title
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
Title
Incidence, severity and causal relationship of treatment-emergent adverse events
Time Frame
through 5 years post-treatment
Title
Incidence and magnitude of abnormal laboratory findings
Time Frame
through 5 years post-treatment
Title
Incidence and severity of abnormal and clinical relevant changes in physical and neurological examinations
Time Frame
through 5 years post-treatment
Title
Incidence and severity of abnormal and clinical relevant changes in body weight
Time Frame
through 5 years post-treatment
Title
Incidence and severity of abnormal and clinical relevant changes in vital signs
Time Frame
through 5 years post-treatment
Title
Incidence and severity of abnormal and clinical relevant changes on electrocardiogram (ECG)
Time Frame
through 5 years post-treatment
Title
Incidence and severity of abnormal and clinical relevant changes in body weight and vital signs
Time Frame
through 5 years post-treatment
Title
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
Title
Incidence and severity of abnormal and clinical relevant changes in Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame
through 5 years post-treatment
Other Pre-specified Outcome Measures:
Title
Percent change from baseline of nadir in C4 levels
Time Frame
through day 30 post-treatment
Title
Percent change from baseline of nadir in platelet levels
Time Frame
through day 30 post-treatment
Title
Percent change from baseline of NAb antibody titers
Time Frame
through day 30 post-treatment
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
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.
The following genetic abnormalities in the dystrophin gene as confirmed by the investigator based on the review of the DMD genetic testing:
Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
MRI Research Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Reed Neurological Research Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center (Investigational Drug Section)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center Drug Information Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA (David Geffen School of Medicine)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA Mattel Children's Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA Outpatient Surgery Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Duke Neurology
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Duke University Medical Center, Lenox Baker Children's Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Biospecimen Repository & Processing Core - BPRC
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke Cardiovascular Magnetic Resonance Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke Children's Hospital & Health Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke University Hospital Investigational Drug Services (IDS) Pharmacy
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
CCTS Clinical Research Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
University of Utah Imaging and Neurosciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
University of Utah Hospital & Clinics Investigational Drug Services
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
University of Utah Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Facility Name
University of Utah Clinical Neurosciences Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C3391001
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
A Study to Evaluate the Safety and Tolerability of PF-06939926 Gene Therapy in Duchenne Muscular Dystrophy
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