ATA-200 gene therapy trial in patients with LGMDR5

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Atamyo Therapeutics

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2024-03-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

ATAMYO THERAPEUTICS

External identifiers

EU CT number

2023-506440-16-00

ClinicalTrials.gov

NCT05973630

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

to assess the safety and tolerability of intravenous administration ATA-200 in pediatric ambulant patients with LGMDR5 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

limb-girdle muscular dystrophy type R5 (previously named LGMD2C)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ambulant male or female patients at least 6 and less than 12 years of age at screening
2. Confirmed LGMDR5 diagnosis before age of 10, based on clinical presentation and genotyping identifying the SGCG gene mutations
3. Able to Perform the 10-meter walk test (10MWT) within 15 sec without help, such as cane, or bilateral help, such as elbow crutches or orthotic devices below the knees and to rise from a standard-height chair with or without arm support
4. Signed written informed consent before any study related procedure is performed
5. Patient medical status sufficiently stable and ability of patient and parents/legal guardian, in the opinion of the investigator, to adhere to the study visits schedule and other protocol requirements.
6. Seronegative patients for neutralizing antibodies against AAV8

Exclusion criteria 14

1. Previous participation in gene and cell therapy trials
2. Any condition that would contraindicate treatment with immunosuppressant therapy
3. Presence of any permanent items (e.g., metal braces) precluding undergoing MRI
4. Any vaccination 1 month prior to the planned IMP administration
5. Serology consistent with HIV exposure or active hepatitis B or C infection
6. Grade 2 or higher lab abnormalities for LFT (except isolated AST increase), bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT, and a PTT, according to current version of CTCAE. Isolated AST increase associated with CK levels > 800 U/L, ALT < 2 x ULN, and GLDH within normal range, is not exclusionary.
7. Known hypersensitivity to IMP excipients, to eculizumab, murine proteins, or any excipients in eculizumab formulation, and to contrast media
8. Cardiomyopathy based on physical and cardiological examination and echocardiography with Left Ventricular Ejection Fraction (LVEF) below 50%
9. Any respiratory assistance, including non-invasive daytime or nocturnal ventilation
10. Inability to cooperate with muscle testing or to perform respiratory function tests
11. Presence or history of concomitant muscular or other medical condition that might interfere with LGMDR5 evolution or that would confound scientific rigor or interpretation of results, e.g., current infectious episode (pulmonary, ENT, etc.), abnormal laboratory test if clinically significant
12. 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
13. Acute illness within 4 weeks of the anticipated IMP administration which may interfere with study assessments
14. Current participation in a clinical trial of another investigational medicinal product

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. incidence of AEs recording throughout the study
2. incidence of clinically relevant abnormalities detection in vital signs
3. physical examination findings
4. vital signs
5. myalgia assessment
6. cardiac assessment
7. laboratory determinations

Secondary endpoints 18

1. Efficacy: muscle Function Tests: North Star Assessment for Neuromuscular Disorders (NSAD) and Performance of the Upper Limb (PUL)
2. Efficacy: timed Function Tests: 10-meter walk test (10MWT); 100-Meter Walk Test (100MWT); Time to Rise From Floor (RFF); 4-Stair climb test
3. Efficacy: muscle Strength Tests: Myotools and Hand Held Dynamometry (HHD)
4. Efficacy: Imaging Assessments: Muscle Nuclear Magnetic Resonance Imaging (NMRI) and spectroscopy: quantitative NMRI (including fat-water separation, based MRI and NMRS) in the lower limbs
5. Efficacy: Respiratory assessments: Pulmonary function tests, including forced vital capacity (FVC), minimal inspiratory/expiratory pressure (MIP/MEP), sniff nasal inspiratory pressure (SNIP) test
6. Efficacy: Respiratory assessments: Respiratory questionnaire
7. Efficacy: Muscle Biopsy: Histological assessment, including centronucleation index and fibrosis assessment
8. Efficacy: Muscle Biopsy: VCN: quantification of vector copy number per diploid cell
9. Efficacy: Muscle Biopsy: SGCG transgene expression (at protein and mRNA levels)
10. Efficacy: Muscle Biopsy: Quantification of human sarcolemmal SGCG-positive fibers by immunohistochemistry
11. Efficacy: Muscle Biopsy: Quantification of human alpha-sarcoglycan positive fibers by immunohistochemistry
12. Efficacy: Muscle Biopsy: Exploratory biomarkers, e.g., TMEM8 for regeneration, FN1 for fibrosis, and CD11b for inflammation, microRNA
13. Efficacy: Patient reported outcome and QoL: Fatigue Visual Analog Scale (VAS)
14. Efficacy: Patient reported outcome and QoL: EQ-5D-Y and EQ-5D-Y proxy 1 questionnaires (based on patient age)
15. Efficacy: Patient reported outcome and QoL: Daily activity living (ACTIVLIM neuromuscular scale)
16. Efficacy: Patient reported outcome and QoL: Change in video outcomes capturing disease hallmarks
17. Efficacy: Biomarkers: Creatine kinase (CK), myomesin-3, circulating microRNA
18. Efficacy: Biomarkers: Blood and urine biobanking

Investigational products

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

Test 1

Auxiliary 3

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

Chief Medical officer

Public contact point

Organisation

Atamyo Therapeutics

Contact name

Chief Medical officer

Third parties 2

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 7 files

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

Application history

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