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A Clinical Study to Assess Safety, Efficacy and Pharmacodynamic Profile of GNT0004 in Duchenne Muscular Dystrophy

ConditionDuchene Muscular Dystrophy
Trial statusRecruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexMale
Age6-10
SponsorGenethon

About this trial

GNT0004 is a recombinant adeno-associated viral (AAV) vector gene therapy composed of an AAV8 serotype capsid containing a sequence-optimized gene for a human microdystrophin. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by dystrophin gene mutations leading to absence of functional dystrophin, a key protein that prevents muscle cell damage during physiological contractions. To address the underlying cause of the disease, GNT0004 delivers an optimized dystrophin gene that is capable to produce a shortened but functional dystrophin protein in target tissues (heart and skeletal muscles) in DMD subjects. It is expected to significantly delay or slow disease progression. GNT0004 will be given as a one-time intravenous (IV) infusion to help it reach muscles throughout the body.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Ambulant male.

Being included in the GNT-014-MDYF study.

6 to 10 years (inclusive).

For participants enrolled in Part 1: BMI scale ≤ 75th percentile. For participants enrolled in Part 2: Body weight ≤ 95th percentile of the BMI or body weight scale.

Disqualifiers

DMD patients with any mutations affecting: exons 1 through 17, for Part 1 participants; affecting exons 8 and/or 9 for Part 2 participants.

Presence of neutralizing antibodies against AAV8.

Cardiomyopathy based on physical/cardiological examination and echocardiography (or cardiac MRI if available).

Any respiratory assistance needed including non-invasive daytime or nocturnal ventilation.

Trial design

Design model

Crossover

Treatments tested in this trial

  • GNT0004 (1x10e13 vg/kg)

    Genetic

    Single intravenous administration of GNT0004

  • GNT0004 (3x10e13 vg/kg)

    Genetic

    Single intravenous administration of GNT0004

  • Placebo

    Genetic

    Single intravenous administration of GNT0004 placebo (IMP placebo)

Treatment groups

77 Participants
are divided into 4 treatment groups
Group A: Part 1 - Cohort 1Experimental treatment 1 intervention
Group B: Part 1 - Cohort 2Experimental treatment 1 intervention
Group C: GNT0004 in Part 2 followed by placebo in Part 3Experimental treatment 2 interventions
Group D: Placebo in Part 2 followed by GNT0004 in Part 3Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

PART 1 - Safety Outcomes: Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), adverse drug reactions (ADRs) and clinically significant laboratory and clinical examination findings

Time frame
From the Screening Visit through the end of Part 1 (Week 12)
2

PART 1 - Immunogenicity Outcomes: Antibodies to AAV8, antibodies to recombinant dystrophin (hMD1) and of cellular immune biomarkers (ELISPOT tests)

Time frame
From the Screening Visit through the end of Part 1 (Week 12)
3

PART 1: Vector shedding quantification in blood, urine, saliva, feces (DNA level)

Time frame
Once a week through Week 12
4

PART 1: Percentage change from baseline on Creatine kinase (CK) in blood over time

Time frame
From the Screening Visit through the end of Part 1 (Week 12)

Secondary outcomes

1

PART 2 - Safety Outcomes: Incidence of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest (AESIs), adverse drug reactions (ADRs) and clinically significant laboratory and clinical examination findings

Time frame
From the Screening Visit through the end of Part 2 (Month 18/Week 78)
2

PART 2: Percentage change from baseline on Creatine kinase (CK) in blood over time

Time frame
From the Screening Visit through the end of Part 2 (Month 18/Week 78)
3

PART 2: Quantification of Microdystrophin positive myofibers level from muscle biopsy at Week 8

Time frame
Week 8
4

PART 2: Quantification of Microdystrophin protein expression from muscle biopsy at Week 8

Time frame
Week 8

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Genethon

Lead sponsor

Source ClinicalTrials.gov
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