ATA-100 gene therapy trial in patients with limb-girdle muscular dystrophy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Atamyo Therapeutics

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

18 Jul 2022 → ongoing

Decision date (initial)

2023-11-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Atamyo Therapeutics

External identifiers

EU CT number

2023-506677-36-00

EudraCT number

2021-004276-33

ClinicalTrials.gov

NCT05224505

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacodynamic, Therapy, Safety

To assess the safety and tolerability of intravenous administration of ATA-100 in ambulant patients with LGMDR9 at two different dosage levels and to select the recommended dose for future studies

Secondary objectives 1

1. To collect preliminary efficacy data

Conditions and MedDRA coding

FKRP-related limb-girdle muscular dystrophy (LGMD R9)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Ambulant male or female patients at least 16 years old
2. Documented LGMDR9 diagnosis based on clinical presentation and genotyping confirming the FKRP gene mutations
3. Able to: i) Perform the 10-meter walk test (10MWT) within 30 sec with unilateral help, such as cane, or bilateral help, such as elbow crutches or orthotic devices below the knees ii) Rise from a standard-height chair with or without arm support
4. Diaphragmatic muscle impairment defined as forced vital capacity (FVC) between 40 and 80% (inclusive) of the expected value
5. Effective contraception
6. Signed written informed consent before any study related procedure is performed
7. Patient medical status sufficiently stable and ability of patient and parents/legal guardian, in the opinion of the Investigator, to adhere to the study visit schedule and other protocol requirements.

Exclusion criteria 16

1. Detectable serum neutralizing antibodies against AAV9
2. Known hypersensitivity to IMP excipients, to eculizumab, murine proteins, or any excipients in eculizumab formulation
3. Cardiomyopathy based on physical and cardiological examination and echocardiography with Left Ventricular Ejection Fraction (LVEF) below 50%
4. Any respiratory assistance, including non-invasive daytime or nocturnal ventilation
5. Inability to cooperate with muscle testing or to perform respiratory function tests
6. Presence or history of concomitant muscular or other medical condition that might interfere with LGMDR9 evolution or that would confound scientific rigor or interpretation of results, e.g., current infectious episode (pulmonary, ENT,...), abnormal laboratory test if clinically significant
7. Acute illness within 4 weeks of the anticipated IMP administration which may interfere with study assessments
8. Recent immunosuppressive treatment within 3 months prior to screening
9. Current or history of significant heart, lung, hepato-biliary or renal disease or impairment that jeopardize the safety of the subject according to the investigator
10. Current participation in a clinical trial of another investigational medicinal product
11. Previous participation in gene and cell therapy trials
12. Any condition that would contraindicate treatment with immunosuppressant therapy
13. Presence of any permanent items (e.g., metal braces) precluding undergoing MRI
14. Any vaccination 1 month prior to the planned IMP administration
15. Serology consistent with HIV exposure or active hepatitis B or C infection
16. Grade 2 or higher lab abnormalities for LFT, bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT, and a PTT, according to current version of CTCAE.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability of ATA-100, as measured by incidence of treatment emergent adverse events, incidence of serious adverse events, and incidence of clinically significant laboratory changes.

Secondary endpoints 6

1. Change from baseline in muscular function tests (NSAD score, 10MWT, etc.) and pulmonary function test (FVC) at one year post-IMP administration
2. Change from baseline in muscle MRI parameters (fat fraction, T2 water content) at one year post-IMP administration
3. Change from baseline in other respiratory assessments (IC, MIP/MEP, SNIP) at one year post-IMP administration
4. Change from baseline in muscle biomarkers (histological features, biodistribution, transgene expression) at one year post-IMP administration
5. Change from baseline in patient reported outcome and quality-of-life assessment (gNMD, Activlim) at one year post-IMP administration
6. Change from baseline in biomarkers (creatine kinase, myomesin-3, circulating microRNA) at one year post-IMP administration

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Atamyo Therapeutics

Sponsor organisation

Atamyo Therapeutics

Address

1 B Rue De L Internationale

City

Evry

Postcode

91000

Country

France

Scientific contact point

Organisation

Atamyo Therapeutics

Contact name

Genethon Clinical Development Department

Public contact point

Organisation

Atamyo Therapeutics

Contact name

Genethon Clinical Development Department

Third parties 9

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 24 files

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

Application history

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