Clinical trial NCT05429372: Study of Fordadistrogene Movaparvovec in Early Stage Duchenne Muscular Dystrophy
Official title: A PHASE 2, MULTICENTER, SINGLE-ARM STUDY TO EVALUATE THE SAFETY AND DYSTROPHIN EXPRESSION AFTER FORDADISTROGENE MOVAPARVOVEC (PF-06939926) ADMINISTRATION IN MALE PARTICIPANTS WITH EARLY STAGE DUCHENNE MUSCULAR DYSTROPHY
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Muscular Dystrophy, Duchenne
Keywords: Early Stage Duchenne Muscular Dystrophy
DMD
gene therapy
fordadistrogene movaparvovec
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-06-23
Enrollment: 10
Sex: MALE
Minimum age (years): 2
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study will evaluate the safety and dystrophin expression following gene therapy in boys with Duchenne Muscular Dystrophy (DMD). It is a single-arm, non-randomized, open-label study

Detailed description: The study will assess the safety and tolerability of fordadistrogene movaparvovec gene therapy. Approximately 10 participants will be enrolled in the study and receive a single IV infusion of PF-06939926; there is no placebo arm. The study includes boys who are at least 2 years old and less than 4 years old (including 3 year olds up until their 4th birthday). All boys will need to be negative for neutralizing antibodies against AAV9, as measured by the test done for the study as part of screening.

The primary analysis will occur when all participants have completed visits through Week 52 (or withdrawn from the study prior to Week 52). All participants will be followed in the study for 5 years after treatment with gene therapy.

Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of DMD by prior genetic testing.

Exclusion Criteria:

* Any of the following genetic abnormalities in the dystrophin gene: a. Any mutation (exon deletion, exon duplication, insertion, or point mutation) affecting any exon between exon 9 and exon 13, inclusive; OR b. A deletion that affects both exon 29 and exon 30; OR c. A deletion that affects any exons between 56-71, inclusive.
* Positive test performed by Pfizer for neutralizing antibodies to AAV9.
* Any prior treatment with gene therapy.
* Any treatment designed to increase dystrophin expression within 6 months prior to screening (including, but not limited to, exon-skipping and nonsense read through).
* Previous or current treatment with oral glucocorticoids or other immunosuppressive agents for the indication of DMD.
* Abnormality in specified laboratory tests, including blood counts, liver and kidney function.

Primary outcomes:
measure: Incidence and severity of Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: Through Week 52
measure: Number of participants with abnormal hematology test results
timeFrame: Through Week 52
measure: Number of participants with abnormal biochemistry test results
timeFrame: Through Week 52
measure: Number of participants with abnormal urine analysis
timeFrame: Through Week 52
measure: Number of participants with abnormal and clinically relevant changes in neurological examinations
timeFrame: Through Week 52
measure: Number of participants with abnormal and clinically relevant changes in body weight
timeFrame: Through Week 52
measure: Number of participants with abnormal and clinically relevant changes in vital signs
timeFrame: Through Week 52
measure: Number of participants with abnormal and clinically relevant changes on cardiac troponin I
timeFrame: Through Week 52
measure: Number of participants with abnormal and clinically relevant changes on electrocardiogram (ECG)
timeFrame: Through Week 52
measure: Number of participants with abnormal and clinically relevant changes on echocardiogram
timeFrame: Through Week 52
Secondary outcomes:
measure: Distribution of mini-dystrophin expression in muscle
timeFrame: At Week 9, Week 52 and Year 5 (if available)
measure: Level of mini-dystrophin expression in muscle
timeFrame: At Week 9, Week 52 and Year 5 (if available)
measure: Incidence and severity of Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: Through 5 years
measure: Number of participants with abnormal hematology test results
timeFrame: Through 5 years
measure: Number of participants with abnormal biochemistry test results
timeFrame: Through 5 years
measure: Number of participants with abnormal urine analysis
timeFrame: Through 5 years
measure: Number of participants with abnormal and clinically relevant changes in neurological examinations
timeFrame: Through 5 years
measure: Number of participants with abnormal and clinically relevant changes in body weight
timeFrame: Through 5 years
measure: Number of participants with abnormal and clinically relevant changes in vital signs
timeFrame: Through 5 years
measure: Number of participants with abnormal and clinically relevant changes on cardiac troponin I
timeFrame: Through 5 years
measure: Number of participants with abnormal and clinically relevant changes on electrocardiogram (ECG)
timeFrame: Through 5 years
measure: Number of participants with abnormal and clinically relevant changes on echocardiogram
timeFrame: Through 5 years
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: CTSI Clinical Research Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Imaging and Neurosciences Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital & Clinics Investigational Drug Services
state: Utah
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neurosciences Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Children's Hospital Melbourne
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: