Clinical Trials List
Protocol NumberCOAV101B12301
NCT Number(ClinicalTrials.gov Identfier)NCT05089656
Completed
2021-11-01 - 2026-02-09
Phase III
Not yet recruiting1
Study ended1
ICD-10G12.9
Spinal muscular atrophy, unspecified
ICD-9335.10
Spinal muscular atrophy, unspecified
A Randomized, Sham-controlled, Double-blind Study to Evaluate the Efficacy and Safety of Intrathecal OAV101 in Type 2 Spinal Muscular Atrophy (SMA) Patients Who Are ≥ 2 to < 18 Years of Age, Treatment Naive, Sitting, and Never Ambulatory
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
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Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- WUH-LIANG HWU 無
- NI-CHUNG LEE 無
- WEN-CHIN WENG 無
- 周書緯 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Principal Investigator
Yuh-Jyh Jong
Kaohsiung Medical Univeristy Chung-Ho Memorial Hospital
Taiwan National PI
鐘育志
The Actual Total Number of Participants Enrolled
0 Study ended
Condition/Disease
Patients aged 2 to under 18 years with treatment-naïve, late-onset type 2 spinal muscular atrophy (SMA) who are able to sit but have never walked.
Objectives
Primary Objective
The primary objective of this study is to compare the efficacy of OAV101 IT versus sham control, as assessed by the change from baseline in the Hammersmith Functional Motor Scale–Expanded (HFMSE) total score. The primary research question is: among patients aged 2 to under 18 years with type 2 spinal muscular atrophy (SMA) who are able to sit but have never walked, carry biallelic pathogenic variants in the SMN1 gene, and have 2 to 4 copies of the SMN2 gene, what is the effect of OAV101 IT compared with a sham injection procedure on the change from baseline in the HFMSE total score, regardless of trial discontinuation or use of prohibited medications after treatment?
Secondary Objectives
The secondary objectives are to compare the efficacy of OAV101 IT versus sham control in two age groups:
Patients aged 2 to under 5 years: evaluated using HFMSE and the Revised Upper Limb Module (RULM);
Patients aged 2 to under 18 years: evaluated using RULM.
In addition, the study aims to assess the safety and tolerability of OAV101 IT compared with sham control in patients aged 2 to under 18 years.
Test Drug
OAV101
Active Ingredient
Onasemnogene abeparvovec
Dosage Form
N/A
Dosage
MG/ML
Endpoints
Efficacy Assessments:
Hammersmith Functional Motor Scale – Expanded (HFMSE)
Revised Upper Limb Module (RULM)
Primary Safety Assessments:
Monitoring of adverse events (AEs)
Vital signs
Age-appropriate neurological examinations
Columbia–Suicide Severity Rating Scale (C-SSRS)
Clinical chemistry, including troponin I and liver enzymes
Hematology (e.g., hemoglobin, hematocrit, white blood cell count, platelet count, red blood cell count)
Coagulation tests
Urinalysis
Pregnancy test
Anthropometric measurements
Electrocardiogram (ECG)
Echocardiography
Neurophysiological monitoring for sensory neuropathy and dorsal root ganglia (DRG) toxicity: sensory nerve action potential (SNAP)
Other Assessments:
The study will include patient-reported outcomes using the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) questionnaire.
Clinical Global Impression – Severity (CGI-S) and Clinical Global Impression – Improvement (CGI-I)
Biomarkers
Humoral immunogenicity
Vector shedding
Hammersmith Functional Motor Scale – Expanded (HFMSE)
Revised Upper Limb Module (RULM)
Primary Safety Assessments:
Monitoring of adverse events (AEs)
Vital signs
Age-appropriate neurological examinations
Columbia–Suicide Severity Rating Scale (C-SSRS)
Clinical chemistry, including troponin I and liver enzymes
Hematology (e.g., hemoglobin, hematocrit, white blood cell count, platelet count, red blood cell count)
Coagulation tests
Urinalysis
Pregnancy test
Anthropometric measurements
Electrocardiogram (ECG)
Echocardiography
Neurophysiological monitoring for sensory neuropathy and dorsal root ganglia (DRG) toxicity: sensory nerve action potential (SNAP)
Other Assessments:
The study will include patient-reported outcomes using the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) questionnaire.
Clinical Global Impression – Severity (CGI-S) and Clinical Global Impression – Improvement (CGI-I)
Biomarkers
Humoral immunogenicity
Vector shedding
Inclution Criteria
Key Inclusion Criteria:
Diagnosis of spinal muscular atrophy (SMA) during the screening period, confirmed by biallelic pathogenic variants in the SMN1 gene and the presence of 2 to 4 copies of the SMN2 gene.
Treatment-naïve for SMN-dependent therapies (e.g., risdiplam [Evrysdi] or nusinersen [Spinraza]).
Age between 2 and <18 years at the time of screening.
Onset of clinical signs and symptoms at ≥6 months of age.
Must have a complete HFMSE assessment performed by a qualified clinical evaluator during screening to confirm eligibility.
Able to sit independently but have never achieved the ability to walk independently at screening.
Independent sitting is defined as the ability to sit with the head upright for at least 10 seconds without using arms or hands to balance or support the body.
Independent walking is defined as the ability to balance the body and take steps forward without assistance.
Diagnosis of spinal muscular atrophy (SMA) during the screening period, confirmed by biallelic pathogenic variants in the SMN1 gene and the presence of 2 to 4 copies of the SMN2 gene.
Treatment-naïve for SMN-dependent therapies (e.g., risdiplam [Evrysdi] or nusinersen [Spinraza]).
Age between 2 and <18 years at the time of screening.
Onset of clinical signs and symptoms at ≥6 months of age.
Must have a complete HFMSE assessment performed by a qualified clinical evaluator during screening to confirm eligibility.
Able to sit independently but have never achieved the ability to walk independently at screening.
Independent sitting is defined as the ability to sit with the head upright for at least 10 seconds without using arms or hands to balance or support the body.
Independent walking is defined as the ability to balance the body and take steps forward without assistance.
Exclusion Criteria
Key Exclusion Criteria:
Anti–AAV9 antibody titer >1:50, as determined by an enzyme-linked immunosorbent assay (ELISA) binding antibody test.
Note: Anti-AAV9 seronegativity is defined as an antibody titer ≤1:50.
Presence of any of the following conditions:
Any active infection requiring systemic antiviral or antimicrobial treatment occurring from the start of screening through the time of OAV101 administration or sham injection.
Any active but untreated viral or bacterial infection occurring from screening through the time of OAV101 administration or sham injection.
Febrile illness occurring within 2 weeks prior to screening, during screening, or up to the baseline visit before OAV101 treatment or sham injection.
Abnormal liver function at the first screening visit, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), or glutamate dehydrogenase (GLDH) > upper limit of normal (ULN) (≥ CTCAE Grade 1).
Note: Isolated elevation of AST without accompanying laboratory abnormalities is not an exclusion criterion.
Requirement for invasive or awake non-invasive ventilatory support for >6 hours within a 24-hour period, or invasive/non-invasive ventilatory support >12 hours total per day, or tracheostomy within 4 weeks prior to screening or baseline.
Presence at screening of any medical condition that, in the investigator’s judgment, could interfere with motor function assessments, including but not limited to:
Severe contractures limiting performance of evaluation tasks (e.g., hip flexion contracture preventing prone testing),
Cobb angle >40° scoliosis, or
Presence of spinal rods.
Body mass index (BMI) below the 3rd percentile for age.
Anti–AAV9 antibody titer >1:50, as determined by an enzyme-linked immunosorbent assay (ELISA) binding antibody test.
Note: Anti-AAV9 seronegativity is defined as an antibody titer ≤1:50.
Presence of any of the following conditions:
Any active infection requiring systemic antiviral or antimicrobial treatment occurring from the start of screening through the time of OAV101 administration or sham injection.
Any active but untreated viral or bacterial infection occurring from screening through the time of OAV101 administration or sham injection.
Febrile illness occurring within 2 weeks prior to screening, during screening, or up to the baseline visit before OAV101 treatment or sham injection.
Abnormal liver function at the first screening visit, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (GGT), or glutamate dehydrogenase (GLDH) > upper limit of normal (ULN) (≥ CTCAE Grade 1).
Note: Isolated elevation of AST without accompanying laboratory abnormalities is not an exclusion criterion.
Requirement for invasive or awake non-invasive ventilatory support for >6 hours within a 24-hour period, or invasive/non-invasive ventilatory support >12 hours total per day, or tracheostomy within 4 weeks prior to screening or baseline.
Presence at screening of any medical condition that, in the investigator’s judgment, could interfere with motor function assessments, including but not limited to:
Severe contractures limiting performance of evaluation tasks (e.g., hip flexion contracture preventing prone testing),
Cobb angle >40° scoliosis, or
Presence of spinal rods.
Body mass index (BMI) below the 3rd percentile for age.
The Estimated Number of Participants
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Taiwan
5 participants
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Global
125 participants
