ADENO-ASSOCIATED VIRUS SEROTYPE 8 EXPRESSING THE HUMAN GAMMA-SARCOGLYCAN GENE for Limb-girdle muscular dystrophy type R5 (LGMDR5) (formerly LGMD2C)

Inclusion criteria

• {"criterion_text":"- Ambulant male or female patients at least 6 and less than 12 years of age at screening\n- Confirmed LGMDR5 diagnosis before age of 10, based on clinical presentation and genotyping identifying the SGCG gene mutations\n- 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\n- Signed written informed consent before any study related procedure is performed\n- 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.\n- Seronegative patients for neutralizing antibodies against AAV8"}

Exclusion criteria

• {"criterion_text":"- Previous participation in gene and cell therapy trials\n- Inability to cooperate with muscle testing or to perform respiratory function tests\n- 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\n- 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\n- Acute illness within 4 weeks of the anticipated IMP administration which may interfere with study assessments\n- Current participation in a clinical trial of another investigational medicinal product\n- Any condition that would contraindicate treatment with immunosuppressant therapy\n- Presence of any permanent items (e.g., metal braces) precluding undergoing MRI\n- Any vaccination 1 month prior to the planned IMP administration\n- Serology consistent with HIV exposure or active hepatitis B or C infection\n- 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.\n- Known hypersensitivity to IMP excipients, to eculizumab, murine proteins, or any excipients in eculizumab formulation, and to contrast media\n- Cardiomyopathy based on physical and cardiological examination and echocardiography with Left Ventricular Ejection Fraction (LVEF) below 50%\n- Any respiratory assistance, including non-invasive daytime or nocturnal ventilation"}

Primary endpoints

• {"endpoint_text":"- incidence of AEs recording throughout the study\n- incidence of clinically relevant abnormalities detection in vital signs\n- physical examination findings\n- vital signs\n- myalgia assessment\n- cardiac assessment\n- laboratory determinations","definition_or_measurement_approach":"- incidence of AEs: recording of adverse events throughout study duration\n- incidence of clinically relevant abnormalities in vital signs: monitoring and detection of clinically relevant changes in recorded vital signs\n- physical examination findings: periodic physical examinations recorded per protocol\n- vital signs: routine measurement of vital signs at scheduled visits\n- myalgia assessment: assessment of muscle pain as recorded per study assessments\n- cardiac assessment: cardiological examinations and assessments (e.g., ECG/echocardiography as applicable)\n- laboratory determinations: routine laboratory tests per protocol"}

Secondary endpoints

• {"endpoint_text":"- Efficacy: muscle Function Tests: North Star Assessment for Neuromuscular Disorders (NSAD) and Performance of the Upper Limb (PUL)\n- Efficacy: timed Function Tests: 10-meter walk test (10MWT); 100-Meter Walk Test (100MWT); Time to Rise From Floor (RFF); 4-Stair climb test\n- Efficacy: muscle Strength Tests: Myotools and Hand Held Dynamometry (HHD)\n- 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\n- Efficacy: Respiratory assessments: Pulmonary function tests, including forced vital capacity (FVC), minimal inspiratory/expiratory pressure (MIP/MEP), sniff nasal inspiratory pressure (SNIP) test\n- Efficacy: Respiratory assessments: Respiratory questionnaire\n- Efficacy: Muscle Biopsy: Histological assessment, including centronucleation index and fibrosis assessment\n- Efficacy: Muscle Biopsy: VCN: quantification of vector copy number per diploid cell\n- Efficacy: Muscle Biopsy: SGCG transgene expression (at protein and mRNA levels)\n- Efficacy: Muscle Biopsy: Quantification of human sarcolemmal SGCG-positive fibers by immunohistochemistry\n- Efficacy: Muscle Biopsy: Quantification of human alpha-sarcoglycan positive fibers by immunohistochemistry\n- Efficacy: Muscle Biopsy: Exploratory biomarkers, e.g., TMEM8 for regeneration, FN1 for fibrosis, and CD11b for inflammation, microRNA\n- Efficacy: Patient reported outcome and QoL: Fatigue Visual Analog Scale (VAS)\n- Efficacy: Patient reported outcome and QoL: EQ-5D-Y and EQ-5D-Y proxy 1 questionnaires (based on patient age)\n- Efficacy: Patient reported outcome and QoL: Daily activity living (ACTIVLIM neuromuscular scale)\n- Efficacy: Patient reported outcome and QoL: Change in video outcomes capturing disease hallmarks\n- Efficacy: Biomarkers: Creatine kinase (CK), myomesin-3, circulating microRNA\n- Efficacy: Biomarkers: Blood and urine biobanking","definition_or_measurement_approach":"- NSAD and PUL: standardized functional scales as listed (North Star Assessment for Neuromuscular Disorders; Performance of the Upper Limb)\n- Timed function tests: timed walking and functional tests (10MWT, 100MWT, RFF, 4SC) per protocol timing and procedures\n- Muscle strength: Myotools (Myo-grip, Myo-pinch) and HHD (MicroFET2) measurements\n- Imaging: quantitative muscle MRI and MR spectroscopy including fat-water separation in lower limbs\n- Respiratory tests: spirometry and measurements including FVC, MIP/MEP, SNIP; plus respiratory questionnaires\n- Muscle biopsy histology: assessment of centronucleation index and fibrosis per histological methods\n- VCN: quantification of vector copy number per diploid cell from biopsy samples\n- SGCG transgene expression: measurement at protein and mRNA levels from biopsy samples\n- Immunohistochemistry quantification of SGCG and alpha-sarcoglycan positive fibers per protocol\n- Exploratory biomarkers: tissue and molecular biomarkers as listed (TMEM8, FN1, CD11b, microRNA)\n- PROs and QoL: Fatigue VAS, EQ-5D-Y (and proxy) and ACTIVLIM per validated questionnaires and age-appropriate versions\n- Video outcomes: standardized video capture and blinded change assessment per protocol\n- Biomarkers CK, myomesin-3, circulating microRNA: blood assays per protocol\n- Biobanking: collection and storage of blood and urine samples"}

Italy

Earliest CTIS Part Ii Submission Date

02-08-2023

Latest Decision Or Authorization Date

20-02-2024

Processing Time Days

202

Number Of Sites

1

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

23-02-2024

Latest Decision Or Authorization Date

10-12-2025

Processing Time Days

656

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Atamyo Therapeutics

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Third parties

• {"country":"Belgium","full_name":"RLM Consulting","duties_or_roles":"Codes: 12; 15 (CT Admin in CTIS)","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Code: 14","organisation_type":"Pharmaceutical company"}