GNT0006 Gene Therapy Trial in Patients With LGMDR9

LGMDR9 Clinical Trial

Official title:

A Phase 1-2 Multicenter Study (2-stages) to Evaluate the Safety and Efficacy of Intravenous GNT0006, Adeno-associated Viral Vector Carrying the FKRP Gene, in Patients With FKRP-related Limb-girdle Muscular Dystrophy (LGMDR9, Formerly LGMD2I)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05224505
• Other study ID #: ATA-001-FKRP
• Secondary ID: 2021-004276-33
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: August 10, 2022
• Est. completion date: October 2030

Study information

• Verified date: April 2023
• Source: Atamyo Therapeutics
• Contact: John Vissing, Pr
• Phone: +4535452562
• Email: john.vissing[@]regionh.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase 1-2 study including a dose escalation safety and proof of concept phase (Stage 1, open label), followed by a double-blind, randomized, placebo-controlled confirmatory phase (Stage 2)

Description:

Multicenter, Phase 1-2 study evaluating safety, pharmacodynamic, efficacy, and immunogenicity of GNT0006, an Adeno-Associated Virus (AAV) vector carrying the human FKRP transgene.

This study will consist of 2 phases: an open-label dose escalation phase (Stage 1) and a double-blind placebo controlled, randomized phase (Stage 2), both with long-term follow-up (LTFU) period.

Stage 1 Two dose cohorts will be enrolled sequentially and enrollment. An initial cohort of three (3) patients will receive a potentially effective dose, followed by a 2nd higher dose cohort of 3 patients.

Stage 2 After selection of the effective dose in Stage 1, thirty-three (33) ambulant patients will be randomized at the optimal selected dose and followed up to the primary efficacy timepoint, i.e., one year after investigational medicinal product (IMP) (or placebo) administration.

At one-year post-IMP administration (timepoint of primary interest for efficacy), patients enrolled in placebo group will receive active IMP while patients randomized in the active IMP group will receive a placebo infusion.

All subjects will be followed for up to 5 years after active IMP (GNT0006) administration.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 39
• Est. completion date: October 2030
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 99 Years

Eligibility

Inclusion Criteria:

• 1. Female and male ambulant patients

• 2. Patients = 16 years old

• 3. Documented LGMDR9 diagnosis based on clinical presentation and genotyping confirming the FKRP gene mutations

• 4. Moderate diaphragmatic muscle impairment

Exclusion Criteria:

• 1. Detectable serum neutralizing antibodies against AAV9

• 2. Cardiomyopathy

Related Conditions & MeSH terms

• LGMDR9

Intervention

Other:
• GNT0006
Single intravenous infusion
• Day 0: Placebo
Single intravenous infusion
• Day 0: GNT0006
Single intravenous infusion
• Day 365 (year 1): Placebo
Single intravenous infusion
• Day 365 (year 1): GNT0006
Single intravenous infusion

Locations

Country	Name	City	State
Denmark	Rigshospitalet, University of Copenhagen Blegdamsvej 9	Copenhagen
France	Institute of Myology Pitié-Salpêtrière Hospital 47 Bd de l'Hôpital	Paris
United Kingdom	Royal Victoria Infirmary Queen Victoria Road Level 6 Leazes Wing	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Atamyo Therapeutics

Countries where clinical trial is conducted

Denmark,  France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change from baseline in Forced Vital Capacity at one year	Primary endpoint	Baseline through 12 months
Secondary	10-Meter Walk test (10MWT)	Secondary endpoint	Baseline through 12 months
Secondary	Timed Up and Go (TUG) test	Secondary endpoint	Baseline through 12 months
Secondary	Change from baseline in North Star Assessment for Neuromuscular Disorders (NSAD) scale (with a range from 0 to 54, the higher the score the better the ability)	Scale to assess patient's abilities necessary to remain functionally ambulant	Baseline through 12 months
Secondary	2-minute walk distance test	Secondary endpoint	Baseline through 12 months
Secondary	Cardiac MRI	To measure cardiac function (left ejection fraction)	Baseline through 12 months
Secondary	Muscle MRI	To measure change from baseline in fat repartition fraction in thigh and leg skeletal muscles	Baseline through 12 months
Secondary	Muscle Biopsy	Quantification of FKRP positive muscle fibers	Baseline through 12 months
Secondary	Muscle Biopsy	Percentage of glycosylation	Baseline through 12 months
Secondary	Patient reported outcome and quality of life assessment	Quality of Life in genetic Neuromuscular Disease (QoL-gNMD), with a range from 0 to 78, the higher the score the worse the quality of life	Baseline through 12 months
Secondary	Patient reported outcome and quality of life assessment	ACTIVLIM, scale measuring level of limitation in performing daily activities (total score ranging from 0 to 44, with the lower score the highest limitation)	Baseline through 12 months