A Phase 3, Randomized, Double-Blind,Placebo-Controlled Study of PF-06939926 in Dmd

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

24 Mar 2025 → ongoing

Decision date (initial)

2024-07-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-508510-42-00

EudraCT number

2019-002921-31

ClinicalTrials.gov

NCT04281485

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To demonstrate superior efficacy of treatment with fordadistrogene movaparvovec as compared to placebo based on change from Baseline in the North Star Ambulatory Assessment (NSAA).

Secondary objectives 8

1. To quantify the mini-dystrophin expression level in the muscle of participants treated with fordadistrogene movaparvovec
2. To characterize the distribution of mini-dystrophin expression in the muscle of participants treated with fordadistrogene movaparvovec
3. To characterize the change in serum creatine kinase (CK) concentration in participants treated with fordadistrogene movaparvovec as compared to placebo.
4. To characterize the skills gained, based on the individual items of the NSAA, in participants treated with PF-06939926 as compared to placebo.
5. To characterize the skills either improved or maintained, based on the individual items of the NSAA, in participants treated with fordadistrogene movaparvovec as compared to placebo.
6. To characterize the 10-meter run/walk velocity in participants treated with PF-06939926 as compared to placebo.
7. To characterize the rise from floor velocity in participants treated with fordadistrogene movaparvovec as compared to placebo.
8. To characterize the functional health status in participants treated with fordadistrogene movaparvovec as compared to placebo.

Conditions and MedDRA coding

DUCHENNE MUSCULAR DYSTROPHY (DMD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Male participants who are ≥4 and <8 years of age at Screening (Visit 1).
2. 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).
3. 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.
4. A NSAA total score >16 and <30 at Screening (Visit 1).
5. Ambulatory, defined as being able to walk 10 meters unassisted, at Screening (Visit 1).
6. 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.
7. 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.
8. 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 17

1. 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.
2. 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.
3. 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.
4. Known cognitive impairment or behavioral issues that would impede the ability to follow instructions, in the judgment of the Investigator, at Screening (Visit 1).
5. 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).
6. Positive test for NAb to AAV9, based on the threshold determined by the Central Laboratory, from a sample taken at Screening (Visit 1)
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. Contraindication to the use of eculizumab, as per the local prescribing information.
14. LVEF <50% on echocardiogram performed at the Screening Visit (Visit 1), as evaluated by the central reader.
15. 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.
16. 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.
17. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline at Week 52 in the NSAA total score.

Secondary endpoints 9

1. 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.
2. Change from Baseline in percent of muscle fibers expressing mini-dystrophin in biceps brachii muscle biopsies at Day 360 as assessed by immunofluorescence.
3. Change from Baseline at Week 52 in serum CK concentration.
4. Number of skills gained at Week 52 based on the individual items of the NSAA.
5. Number of skills either improved or maintained at Week 52 based on the individual items of the NSAA.
6. Change from Baseline at Week 52 in the 10 meter run/walk velocity.
7. Change from Baseline at Week 52 in the rise from floor velocity.
8. Change from Baseline at Week 52 in the Modified Pediatric Outcomes Data Collection Instrument (PODCI): Transfer and Basic Mobility Core Scale (Pediatric Parent).
9. Change from Baseline at Week 52 in the Modified PODCI: Sports and Physical Functioning Core Scale (Pediatric Parent).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 8

Locations

5 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 5 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 89 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications