GNT0006 Gene Therapy Trial in Patients With LGMDR9

• ClinicalTrials.gov Identifier: NCT05224505
• Recruitment Status: Recruiting
• First Posted: February 4, 2022
• Sponsor: Atamyo Therapeutics
• Information provided by (Responsible Party): Atamyo Therapeutics

Study Description

Brief 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)

Condition or disease	Intervention/treatment	Phase
LGMDR9	Other: GNT0006; Other: Day 0: Placebo; Other: Day 0: GNT0006; Other: Day 365 (year 1): Placebo; Other: Day 365 (year 1): GNT0006	Phase 1; Phase 2

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Stage 1: single administration of GNT0006, open label Stage 2: randomized, placebo-controlled, double blind. One cohort will receive single administration of GNT0006 followed by a single administration of placebo one year after. The second cohort will receive single administration of placebo followed by a single administration of GNT0006 one year after
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Blinding for Stage 2 will be ensured until the last subject has received all treatments
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: August 10, 2022
• Estimated Primary Completion Date: October 2025
• Estimated Study Completion Date: October 2030

Arms and Interventions

Arm	Intervention/treatment
Experimental: GNT0006 - Stage 1; 6 patients treated with GNT0006 in Stage 1 (open label) 2 dose cohorts : Cohort 1: single intravenous injection 9.0E+12 vg/Kg Cohort 2: single intravenous injection 2.7E+13 vg/Kg	Other: GNT0006; Single intravenous infusion
Experimental: GNT0006 - Stage 2; 22 patients randomized in single intravenous GNT0006 arm at selected dose in Stage 2 (double blind). The patients will receive placebo one year after to maintain the blind	Other: Day 0: GNT0006; Single intravenous infusion; Other: Day 365 (year 1): Placebo; Single intravenous infusion
Placebo Comparator: Placebo - Stage 2; 11 patients randomized in placebo arm in Stage 2 (double blind). The patients will receive single intravenous GNT0006 at selected dose one year after to maintain the blind	Other: Day 0: Placebo; Single intravenous infusion; Other: Day 365 (year 1): GNT0006; Single intravenous infusion

Outcome Measures

Primary Outcome Measures :

1. Percent change from baseline in Forced Vital Capacity at one year [ Time Frame: Baseline through 12 months ]
   Primary endpoint

Secondary Outcome Measures :

1. 10-Meter Walk test (10MWT) [ Time Frame: Baseline through 12 months ]
   Secondary endpoint
2. Timed Up and Go (TUG) test [ Time Frame: Baseline through 12 months ]
   Secondary endpoint
3. 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) [ Time Frame: Baseline through 12 months ]
   Scale to assess patient's abilities necessary to remain functionally ambulant
4. 2-minute walk distance test [ Time Frame: Baseline through 12 months ]
   Secondary endpoint
5. Cardiac MRI [ Time Frame: Baseline through 12 months ]
   To measure cardiac function (left ejection fraction)
6. Muscle MRI [ Time Frame: Baseline through 12 months ]
   To measure change from baseline in fat repartition fraction in thigh and leg skeletal muscles
7. Muscle Biopsy [ Time Frame: Baseline through 12 months ]
   Quantification of FKRP positive muscle fibers
8. Muscle Biopsy [ Time Frame: Baseline through 12 months ]
   Percentage of glycosylation
9. Patient reported outcome and quality of life assessment [ Time Frame: Baseline through 12 months ]
   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
10. Patient reported outcome and quality of life assessment [ Time Frame: Baseline through 12 months ]
    ACTIVLIM, scale measuring level of limitation in performing daily activities (total score ranging from 0 to 44, with the lower score the highest limitation)

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: John Vissing, Pr; +4535452562; john.vissing@regionh.dk

Locations

Denmark

Rigshospitalet, University of Copenhagen Blegdamsvej 9; Recruiting

Copenhagen, Denmark, 2100

Contact: John Vissing, Pr +45 35452562 john.vissing@regionh.dk

France

Institute of Myology Pitié-Salpêtrière Hospital 47 Bd de l'Hôpital; Recruiting

Paris, France, 75013

Contact: Tanya Stojkovic, Dr +33 (0) 1 42 16 58 63 essais-adultes@institut-myologie.org

United Kingdom

Royal Victoria Infirmary Queen Victoria Road Level 6 Leazes Wing; Recruiting

Newcastle Upon Tyne, United Kingdom, NE1 4LP

Contact: Volker Straub, Pr +44 (0) 191 241 8762 volker.straub@newcastle.ac.uk

Sponsors and Collaborators

Atamyo Therapeutics

More Information

• Responsible Party: Atamyo Therapeutics
• ClinicalTrials.gov Identifier: NCT05224505
• Other Study ID Numbers: ATA-001-FKRP; 2021-004276-33 ( EudraCT Number )
• First Posted: February 4, 2022
• Last Update Posted: April 6, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Muscular Dystrophies, Limb-Girdle; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, Inborn