GNT0006 Gene Therapy Trial in Patients With LGMDR9

• Sponsor: Atamyo Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05224505
• Collaborator: (none)
• Enrollment: 39
• Locations: 3
• Arms: 3
• Anticipated Duration (Months): 97.7
• Patients Per Site: 13
• Patients Per Site Per Month: 0.1

Study Details

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
• Anticipated 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 afterStage 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: Aug 10, 2022
• Anticipated Primary Completion Date: Oct 1, 2025
• Anticipated Study Completion Date: Oct 1, 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 [Baseline through 12 months]

   Primary endpoint

Secondary Outcome Measures

1. 10-Meter Walk test (10MWT) [Baseline through 12 months]

   Secondary endpoint

2. Timed Up and Go (TUG) test [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) [Baseline through 12 months]

   Scale to assess patient's abilities necessary to remain functionally ambulant

4. 2-minute walk distance test [Baseline through 12 months]

   Secondary endpoint

5. Cardiac MRI [Baseline through 12 months]

   To measure cardiac function (left ejection fraction)

6. Muscle MRI [Baseline through 12 months]

   To measure change from baseline in fat repartition fraction in thigh and leg skeletal muscles

7. Muscle Biopsy [Baseline through 12 months]

   Quantification of FKRP positive muscle fibers

8. Muscle Biopsy [Baseline through 12 months]

   Percentage of glycosylation

9. Patient reported outcome and quality of life assessment [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 [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

Criteria

• Ages Eligible for Study: 16 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. Female and male ambulant patients
• 1. Patients ≥ 16 years old
• 1. Documented LGMDR9 diagnosis based on clinical presentation and genotyping confirming the FKRP gene mutations
• 1. Moderate diaphragmatic muscle impairment

Exclusion Criteria:

• 1. Detectable serum neutralizing antibodies against AAV9
• 1. Cardiomyopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rigshospitalet, University of Copenhagen Blegdamsvej 9	Copenhagen		Denmark	2100
2	Institute of Myology Pitié-Salpêtrière Hospital 47 Bd de l'Hôpital	Paris		France	75013
3	Royal Victoria Infirmary Queen Victoria Road Level 6 Leazes Wing	Newcastle Upon Tyne		United Kingdom	NE1 4LP

Sponsors and Collaborators

• Atamyo Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Atamyo Therapeutics
• ClinicalTrials.gov Identifier: NCT05224505
• Other Study ID Numbers: ATA-001-FKRP; 2021-004276-33
• First Posted: Feb 4, 2022
• Last Update Posted: Aug 24, 2022
• Last Verified: Aug 1, 2022

• 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

Study Results

No Results Posted as of Aug 24, 2022