CTRI Number	CTRI/2021/11/037956 [Registered on: 11/11/2021] Trial Registered Prospectively
Last Modified On:	16/01/2024
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Biological
Study Design	Randomized, Parallel Group, Placebo Controlled Trial
Public Title of Study Modification(s)	Randomized, placebo-controlled, double-blind trial of intrathecal (IT) OAV101 administration in patients with later onset Type 2 spinal muscular atrophy (SMA), to evaluate the efficacy and safety.
Scientific Title of Study	A randomized, sham-controlled, double-blind study to evaluate the efficacy and safety of intrathecal (IT) OAV101 in patients with later onset Type 2 spinal muscular atrophy (SMA) who are greater than or equal to 2 years to less than 18 years of age, treatment naive, sitting, and never ambulatory
Secondary IDs if Any	Secondary ID  Registry  2021-003474-31  EudraCT  COAV101B12301; Version 0.0; Date 23 Jul 2021  Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)	Name  Murugananthan K  Address  Novartis Healthcare Private Limited 6 and 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai MAHARASHTRA 400051 India  Phone  912250243544   Fax     Email  murugananthan.k@novartis.com
Details Contact Person Scientific Query	Name  Murugananthan K  Address  Novartis Healthcare Private Limited 6 and 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai MAHARASHTRA 400051 India  Phone  912250243544   Fax     Email  murugananthan.k@novartis.com
Details Contact Person Public Query	Name  Murugananthan K  Address  Novartis Healthcare Private Limited 6 and 7 floor Inspire BKC G Block BKC Main Road Bandra Kurla Complex Bandra (East) Mumbai Mumbai MAHARASHTRA 400051 India  Phone  912250243544   Fax     Email  murugananthan.k@novartis.com
Source of Monetary or Material Support	Novartis Pharma AG, Novartis Campus 4056 – Basel, Switzerland
Primary Sponsor	Name  Novartis Healthcare Pvt Ltd  Address  6 & 7 floor, Inspire BKC, G Block, BKC Main Road, Bandra Kurla Complex, Bandra (East), Mumbai – 400051,India  Type of Sponsor  Pharmaceutical industry-Global
Details of Secondary Sponsor	Name  Address  NIL  NIL
Countries of Recruitment	Brazil China Colombia Denmark India Malaysia Mexico Russian Federation Saudi Arabia Singapore South Africa Taiwan Thailand United States of America Viet Nam Egypt
Sites of Study Modification(s)	No of Sites = 7   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Dr Ramesh Konanki  "Rainbow Children’s Hospital Medicare Ltd,  H. No: 3-7-222/223, Sy No 51-54, Polica Station Main Road, Karkhana, Secunderabad, Telangana-500009" Hyderabad   9355400361 drkonankiramesh@rainbowhospitals.in  Dr Sheffali Gulati  All India Institute of Medical Sciences  Department of Pediatrics, Ansari Nagar, New Delhi- 110029 New Delhi   91-11-26588641 sheffaligulati@gmail.com  DrSmilu Mohanlal  Aster MIMS Hospital  Kommeri Bypass Rd, Govindapuram, Kozhikode, Kerala 673016 Kozhikode   9633889777 smilu.mohanlal@asterhospital.com  Dr Ann Agnes Mathew  Aster RV Hospital  4th floor, Department of Pediatrics, Aster RV Hospital, CA 37 24th Main Road, ITI layout, 1st Phase, JP Nagar Bengaluru, Karnataka 560078 India. Bangalore   8066040400 annagnesmathew@yahoo.co.in  Dr Neelu Desai  P. D Hinduja Hospital and Medical Research Centre  8-12, SVS Rd, Mahim West, Mahim, Mumbai, Maharashtra 400016 Mumbai   9920614333 neelushahdesai@gmail.com  Dr Sanjukta De  Peerless Hospitex Hospital and Research Center Limited,  360, Panchsayar, Kolkatta-700094, West Bengal, India. Kolkata   03340111222 dey.sanjukta@gmail.com  Dr Ratna Dua Puri  Sir Gangaram Hospital  Institute of Medical Genetics and Genomics, Sir Gangaram Hospital Marg, Rajinder Nagar, New Delhi-110060 New Delhi   9811869192 ratnadpuri@yahoo.com
Details of Ethics Committee Modification(s)	No of Ethics Committees= 7   Name of Committee  Approval Status  IEC- DR Ramesh Konanki  Approved  IEC- Dr Sanjukta DE  Approved  IEC- DR. Ann Mathew  Approved  IEC-Dr Smilu  Approved  Institute Ethics Committee AIIMS, Dr. Sheffali Gulati  Approved  Institution ethics committee- Dr Neelu Desai   Approved  Sir Gangaram hospital Ethics Commitee, Dr. Ratna Dua Puri  Approved
Regulatory Clearance Status from DCGI Modification(s)	Status  Approved/Obtained
Health Condition / Problems Studied	Health Type  Condition  Patients  Other inherited spinal muscular atrophy
Intervention / Comparator Agent	Type  Name  Details  Intervention  OAV101  Single intrathecal dose of 1.2 x 1014 vector genomes   Comparator Agent  Sham Procedure  It consists of a small needle prick on the lower back at the location where the lumbar puncture injection is normally made. The needle will break the skin but no needle insertion for lumbar puncture will occur.
Inclusion Criteria	Age From  2.00 Year(s) Age To  18.00 Year(s) Gender  Both  Details  - Diagnostic confirmation during screening period of SMA caused by biallelic SMN1 pathogenic variants affecting SMN1 and 2-4 copies of SMN2 - The patient must be treatment naive for all SMN dependent therapies (e.g., risdiplam (Evrysdi) and nusinersen (Spinraza)). - ≥ 2 years and < 18 years of age at time of screening - Onset of clinical signs and symptoms at ≥ 6 months of age - Patient must have a complete HFMSE assessment, with available total score as administered by qualified clinical evaluator during the screening period for trial eligibility - Able to sit independently at screening, but has never had the ability to walk independently. --Definition of sitting independently: Child sits up straight with the head erect for at least 10 seconds without using arms or hands to balance body or support position (Wijnhoven et al 2004). --Definition of walking independently: The child is able to balance the body and control forward stepping movements without assistance (Wijnhoven et al 2004).
ExclusionCriteria	Details  - Anti-adeno-associated virus serotype 9 (AAV9) antibody titers > 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) binding immunoassay. NOTE: A negative anti-AAV9 antibody titer is defined as ≤ 1:50. - Presence of the following: . An active infectious process requiring systemic antiviral or antimicrobial therapy at any time between onset of screening and dosing of OAV101 or the sham procedure · An active but untreated viral or bacterial infectious process at any time between onset of screening and dosing of OAV101 or the sham procedure · Any febrile illness within two weeks prior to start of screening, during screening period or during baseline period up to OAV101 treatment or sham procedure · Hepatic dysfunction (i.e., aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH), > upper limit of normal (ULN) (Common Terminology Criteria for Adverse Events (CTCAE) grade1 or greater) at Screening Visit 1. NOTE: In the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary · Requiring invasive or awake noninvasive ventilation for > 6 hours during a 24-hour period, invasive or noninvasive ventilation for > 12 hours during a 24-hour period, or requiring tracheostomy during the 4 weeks prior to screening or baseline. · Complications at screening, as determined by theInvestigator, that would interfere with motor efficacy assessments . Body mass index (BMI) < 3rd percentile
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Centralized
Blinding/Masking	Participant, Investigator and Outcome Assessor Blinded
Primary Outcome	Outcome  TimePoints  Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to 18 years age group  Week 52
Secondary Outcome	Outcome  TimePoints  . Change from baseline in HFMSE total score at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to 5 years age group • Change from baseline in RULM at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to 18 years age group • Change from baseline in the RULM at the end of Follow-up Period 1 in treated patients compared to sham controls in the ≥ 2 to 5 years age group  Week 52
Target Sample Size Modification(s)	Total Sample Size="125" Sample Size from India="30"
Phase of Trial	Phase 3
Date of First Enrollment (India)	21/02/2022
Date of First Enrollment (Global)	21/12/2021
Estimated Duration of Trial	Years="3" Months="0" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Closed to Recruitment of Participants
Recruitment Status of Trial (India)	Closed to Recruitment of Participants
Publication Details Modification(s)	NIL
Brief Summary	The purpose of this phase III multi-center, single dose (1.2 x 1014 vector genomes), randomized, sham-controlled, double-blind trial is to investigate the safety, tolerability, and efficacy of intrathecal (IT) OAV101 in treatment naive, sitting and never ambulatory Type 2 SMA patients ≥ 2 to < 18 years who harbor biallelic SMN1 pathogenic variants in SMN1 and 2 to 4 copies of SMN2. This is a randomized, double-blind, sham-controlled study to evaluate the clinical efficacy, safety, and tolerability over 52 weeks of a single, nominal dose (1.2 x 1014 vector genomes) of intrathecal OAV101 in patients with Type 2 SMA who are ≥ 2 to < 18 years of age, able to sit, but have never walked. The 5q SMA study population harbors biallelic SMN1 pathogenic variants and 2 to 4 SMN2 copies. Approximately 125 patients aged ≥2 to <18 years will be recruited consisting of ∼65 patients between the ages of ≥ 2 to < 5 years and ∼60 patients between the ages of ≥ 5 to < 18 years. Participants will be randomized in a 3:2 ratio to receive OAV101 (1.2 x 1014 vector genomes) by lumbar intrathecal injection (n=~75) or to receive a sham procedure (n=~50).