FORDADISTROGENE MOVAPARVOVEC for Duchenne muscular dystrophy

Inclusion criteria

• {"criterion_text":"- Male participants who are ≥4 and <8 years of age at Screening (Visit 1).\n- Confirmed diagnosis of DMD by prior genetic testing demonstrating the presence of a mutation in the dystrophin gene consistent with DMD at Screening (Visit 1). If the Investigator determines that the results are inconclusive, a repeat genetic testing will be allowed through the central laboratory at Screening (Visit 1).\n- Receipt of a stable daily dose of glucocorticoids (≥0.5 mg/kg/day prednisone, prednisolone, or ≥0.75 mg/kg/day deflazacort) for at least 3 months prior to Screening (Visit 1) and during the period between Screening (Visit 1) and Day 1 (Visit 3). In order to comply with protocol procedures, there should also be a reasonable expectation that this daily dose of glucocorticoids will remain stable for the first 2 years of the study. A stable dose is defined as one in which any change is ≤0.2 mg/kg.\n- A NSAA total score >16 and <30 at Screening (Visit 1).\n- Ambulatory, defined as being able to walk 10 meters unassisted, at Screening (Visit 1).\n- Participants/legally acceptable representatives who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures including, potentially, open muscle biopsies under general anesthesia and cardiac MRI under general anesthesia.\n- Participants/legally acceptable representatives who are capable of giving assent/signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the assent/informed consent document (ICD) and in this protocol.\n- Participants/legally acceptable representatives who are willing to protect the integrity of the study data by not actively seeking sensitive clinical data (eg, CK, ALT, AST, NAb to AAV9) through independent laboratory tests and by not sharing trial experiences with other participants or publicly (eg, through social media)."}

Exclusion criteria

• {"criterion_text":"- Prior treatment with gene therapy, defined as any therapy introducing exogenous DNA or intended to permanently alter the endogenous DNA. Gene therapy (other than IP) will be prohibited for the duration of the study.\n- Acute infection at Screening (Visit 1) or Baseline (Visit 2) that, in the judgement of the Investigator is not expected to be fully resolved at least 2 weeks before Day 1 (Visit 3). At Day 1 (Visit 3), participants must have been infection-free for at least 2 weeks prior to IP administration. Delay of IP administration for up to 14 days is permitted to enable infections to become fully resolved.\n- Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.\n- Known hypersensitivity to any of the components of the IP or solution for infusion, such as hypersensitivity to albumin or a diagnosis of HFI. Symptoms suggestive of HFI include nausea, vomiting, bloating, stomach cramps, or diarrhea following the ingestion of sweet foods or drinks, or a pattern of avoiding sweet foods or drinks.\n- Contraindication to the use of eculizumab, as per the local prescribing information.\n- LVEF <50% on echocardiogram performed at the Screening Visit (Visit 1), as evaluated by the central reader.\n- Participants with the following genetic abnormalities in the dystrophin gene as confirmed by the investigator based on the review of DMD genetic testing: 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.\n- Cardiac pathologies, as evaluated by a pediatric cardiologist at the Screening Visit (Visit 1): a. Diagnosis of myocarditis (eg, viral): either based on prior medical history or based on findings in cardiac imaging tests; b. Any other cardiac history, and/or condition and/or abnormalities in cardiac imaging, that determine that the participant should not be included in the study, as per the cardiologist.\n- Not a candidate for mechanical cardiac or respiratory support, or any other invasive intervention, if indicated for management of an acute event as determined by the cardiologist in consultation with the investigator at the Screening Visit (Visit 1).\n- Exposure within 6 months prior to Screening (Visit 1) to any treatment designed to increase dystrophin expression (including, but not limited to exon-skipping and nonsense read-through). These treatments will also be prohibited during the period between Screening (Visit 1) and Day 1 (Visit 3) and for the first 52 weeks of the study. Please note that for participants who are eligible for these treatments: Participants may be enrolled who have previously experienced lack of efficacy, or intolerance, as long as they received their last dose more than 6 months before screening (Visit 1), or who have refused these treatments. Participants receiving these treatments from which there is believed to be benefit should not discontinue them in order to meet this exclusion criterion and enroll in the study.\n- Previous administration with an investigational drug or investigational vaccine within 30 days (or as determined by the local requirement) or 5 half-lives (whichever is longer) at Screening (Visit 1). These treatments will also be prohibited during the period between Screening (Visit 1) and Day 1 (Visit 3) and for the first 2 years of the study.\n- Known cognitive impairment or behavioral issues that would impede the ability to follow instructions, in the judgment of the Investigator, at Screening (Visit 1).\n- Any nonhealed injury at Screening (Visit 1) which, in the opinion of the Investigator, may impact functional testing; additionally, lower limb fractures must have been healed for at least 3 months prior to Screening (Visit 1).\n- Positive test for NAb to AAV9, based on the threshold determined by the Central Laboratory, from a sample taken at Screening (Visit 1)\n- Receipt of a live attenuated vaccination within 30 days prior to Screening (Visit 1). Receipt of a live attenuated vaccination will also be prohibited for 90 days before Day 1 (Visit 3), for 90 days prior to Year 2 IP administration, and for the first 2 months after each IP administration.\n- Abnormality in hematology or chemistry profiles at Screening (Visit 1). A single repeat for value(s) outside allowable limits is permitted to re-assess eligibility: a. Absolute neutrophil count <1000 cells/mm3; b. Platelets <150 x 103/μl; c. Cystatin C >1.2 x ULN; d. Positive hepatitis A virus (anti-HAV) immunoglobulin M, hepatitis B surface antigen (HbsAg), and/or hepatitis C antibody (HCVAb); e. Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following: 1. Prothrombin time (PT) > upper limit of normal (ULN); prolonged international normalized ratio (INR) >ULN; 2. GLDH >2 x ULN; 3. Total bilirubin >1.5 x ULN (unless the participant has a history of Gilbert disease) and direct bilirubin >0.5 mg/dL; 4. Gamma-glutamyl transferase (GGT) >1.5 x ULN.\n- Other acute or chronic medical or psychiatric condition at Screening (Visit 1), including recent (within the past year) or active suicidal ideation or behavior (using screening by the Child Behavior Check List (CBCL) and determined by the Investigator, as described in Section 8.2.13) or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the participant inappropriate for entry into this study."}

Primary endpoints

• {"endpoint_text":"- Change from Baseline at Week 52 in the NSAA total score.","definition_or_measurement_approach":"Change from baseline measured at Week 52 using the North Star Ambulatory Assessment (NSAA) total score."}

Secondary endpoints

• {"endpoint_text":"- Change from Baseline in percent normal mini-dystrophin expression level in biceps brachii muscle biopsies at Day 360 using a liquid chromatography mass spectrometry (LC-MS) assay.","definition_or_measurement_approach":"Measured in biceps brachii muscle biopsies at Day 360 using an LC-MS assay; reported as percent normal mini-dystrophin expression level change from baseline."}
• {"endpoint_text":"- Change from Baseline in percent of muscle fibers expressing mini-dystrophin in biceps brachii muscle biopsies at Day 360 as assessed by immunofluorescence.","definition_or_measurement_approach":"Assessed by immunofluorescence on biceps brachii biopsies at Day 360; reported as percent of muscle fibers expressing mini-dystrophin change from baseline."}
• {"endpoint_text":"- Change from Baseline at Week 52 in serum CK concentration.","definition_or_measurement_approach":"Serum creatine kinase (CK) concentration change from baseline measured at Week 52."}
• {"endpoint_text":"- Number of skills gained at Week 52 based on the individual items of the NSAA.","definition_or_measurement_approach":"Count of individual NSAA items showing skill gains at Week 52 compared to baseline."}
• {"endpoint_text":"- Number of skills either improved or maintained at Week 52 based on the individual items of the NSAA.","definition_or_measurement_approach":"Count of individual NSAA items that are improved or maintained at Week 52 versus baseline."}
• {"endpoint_text":"- Change from Baseline at Week 52 in the 10 meter run/walk velocity.","definition_or_measurement_approach":"Change in 10-meter run/walk velocity measured at Week 52 compared to baseline."}
• {"endpoint_text":"- Change from Baseline at Week 52 in the rise from floor velocity.","definition_or_measurement_approach":"Change in rise-from-floor velocity measured at Week 52 compared to baseline."}
• {"endpoint_text":"- Change from Baseline at Week 52 in the Modified Pediatric Outcomes Data Collection Instrument (PODCI): Transfer and Basic Mobility Core Scale (Pediatric Parent).","definition_or_measurement_approach":"Change from baseline at Week 52 on the Modified PODCI Transfer and Basic Mobility Core Scale (parent-reported)."}
• {"endpoint_text":"- Change from Baseline at Week 52 in the Modified PODCI: Sports and Physical Functioning Core Scale (Pediatric Parent).","definition_or_measurement_approach":"Change from baseline at Week 52 on the Modified PODCI Sports and Physical Functioning Core Scale (parent-reported)."}

Belgium

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

634

Number Of Sites

2

Number Of Participants

5

France

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

634

Number Of Sites

2

Number Of Participants

5

Germany

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

665

Number Of Sites

1

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

665

Number Of Sites

2

Number Of Participants

13

Spain

Earliest CTIS Part Ii Submission Date

26-04-2024

Latest Decision Or Authorization Date

20-01-2026

Processing Time Days

634

Number Of Sites

3

Number Of Participants

21

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

ICON PLC

Responsibilities

Anti-drug antibodies (ADA) to mini-dystrophin (anti-transgene protein Ab)During Study Storage and An

Name

Medpace Inc.

Responsibilities

Medical image

Name

Ppd Inc.

Name

Fortrea Inc.

Responsibilities

Home health

Name

Labcorp Central Laboratory Services LP

Responsibilities

CENTRAL LAB SERVICES, BIOANALYTICAL SERVICES

Name

Monogram Biosciences Inc.

Responsibilities

Neutralizing Antibody (NAb) to adenoassociated virus, serotype 9 (AAV9)During Study Storage and Ana

Name

Cellular Technology Ltd.

Responsibilities

BIOANALYTICAL SERVICES - Elispot testing

Third parties

• {"country":"United States","full_name":"ICON PLC","duties_or_roles":"Anti-drug antibodies (ADA) to mini-dystrophin (anti-transgene protein Ab)During Study Storage and An","organisation_type":"Industry"}
• {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"Training development and delivery - NSAA Rater training","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Cellular Technology Ltd.","duties_or_roles":"BIOANALYTICAL SERVICES - Elispot testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"CENTRAL LAB SERVICES, BIOANALYTICAL SERVICES","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Monogram Biosciences Inc.","duties_or_roles":"Neutralizing Antibody (NAb) to adenoassociated virus, serotype 9 (AAV9)During Study Storage and Ana","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"Home health","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Inc.","duties_or_roles":"Medical image","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}