Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
131
Countries
3
Sites
6
Spinal Muscular Atrophy
To collect long-term follow-up safety and efficacy data in patients with spinal muscular atrophy (SMA) who were treated with AVXS-101 (also known as OAV101) in a Novartis Pharma AG -sponsored clinical trial, including but not limited to AVXS-101-CL-102 (Phase 1), AVXS-101-CL302 (Phase 3), AVXS-101-CL-303 (Phase 3), AVX…
Key facts
- Sponsor
- Novartis Pharma AG
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 16 Jun 2020 → ongoing
- Decision date (initial)
- 2024-06-26
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Novartis Pharma AG
External identifiers
- EU CT number
- 2024-513086-39-00
- EudraCT number
- 2019-002611-26
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Safety
To collect long-term follow-up safety and efficacy data in patients with spinal muscular atrophy (SMA) who were treated with AVXS-101 (also known as OAV101) in a Novartis Pharma AG -sponsored clinical trial, including but not limited to AVXS-101-CL-102 (Phase 1), AVXS-101-CL302 (Phase 3), AVXS-101-CL-303 (Phase 3), AVXS-101-CL-304 (Phase
3) or AVXS-101-CL-306 (Phase 3)
Conditions and MedDRA coding
Spinal Muscular Atrophy
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10079415 | Spinal muscular atrophy type III | 10010331 |
| 20.0 | LLT | 10079413 | Spinal muscular atrophy type I | 10010331 |
| 20.0 | LLT | 10079416 | Spinal muscular atrophy type II | 10010331 |
Study design 2 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Long-term Follow-up Study without IMP - initial follow up phase For the initial follow-up phase of the study which will last 5 years, patients will return to an investigative site. For the first two years, the patient will be seen every
6 months. Thereafter, annual follow-up will be conducted on Years 3 to 5 visits.
|
Not Applicable | None | ||
| 2 | Long-term Follow-up Study without IMP - observational phase Upon completion of the initial 5-year follow-up phase, patients will enter the observational phase where patients/caregivers will be contacted via telephone annually for remote assessments for up to 10 years
|
Not Applicable | None |
Regulatory references
- Scientific advice from competent authorities
- European Medicines Agency
- Plan to share IPD
- Yes
- IPD plan description
- Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 2
- Any patient with SMA who received AVXS-101 gene replacement therapy in a Novartis Pharma AG -sponsored clinical study
- Patient/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule
Exclusion criteria 1
- Patient/parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 20
- Number of participants who reach developmental milestones
- Change from baseline in Hammersmith Functional Motor Scale - Expanded (HFMSE) score
- Change from baseline in Revised Upper Limb Module (RULM)
- Change from baseline in Bayley Scales of Infant and Toddler Development (Bayley-III)
- Change from baseline in Cogstate Computerized Cognitive Battery
- Change from baseline in Clinical Evaluation of Language Fundamentals (CELF-5)
- Change from baseline in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND)
- Number of participants who experience a clinically significant change from baseline in pulmonary assessment results and require ventilatory support
- Number of participants who experience swallowing dysfunction and require nutritional support
- Number of participants who experience a clinically significant change from baseline in physical examination findings
- Number of participants who experience a clinically significant change from baseline in vital signs measurements
- Change from baseline in height measurements
- Change from baseline in weight measurements
- Number of participants who experience a clinically significant change from baseline in clinical laboratory assessments
- Number of participants who experience a clinically significant change from baseline in cardiac assessments
- Number of participants who experience a clinically significant change from baseline in observational phase questionnaire results
- Concomitant Medications
- Any other treatment for SMA for the observational phase
- Number of participants who experience at least one serious adverse event (SAE)
- Number of participants who experience at least one adverse event of special interest (AESI)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Zolgensma 2 × 10^13 vector genomes/mL solution for infusion
PRD8079948 · Product
- Active substance
- Onasemnogene Abeparvovec
- Substance synonyms
- DNA (synthetic adeno-associated virus 9 vector scAAV9.CB.hSMN human survivor motor neuron protein-specifying), Non-replicating recombinant self-complementary adeno-associated viral serotype 9 vector containing the cDNA of the survival of motor neuron 2 gene under the control of the hybrid cytomegalovirus enhancer/chicken beta-actin promoter, Non-replicating recombinant scAAV9 vector containing the cDNA of the SMN2 gene under the control of the hybrid CMV enhancer/CBA promoter, AVXS-101
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0.00 Other
- Max total dose
- 0.00 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- M09AX09 — -
- Marketing authorisation
- EU/1/20/1443/001
- MA holder
- NOVARTIS EUROPHARM LIMITED
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- Yes
- Orphan designation number
- EU/3/15/1509
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Novartis Pharma AG
- Sponsor organisation
- Novartis Pharma AG
- Address
- Lichtstrasse 35
- City
- Basel
- Postcode
- 4056
- Country
- Switzerland
Scientific contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Katharina Boehm
Public contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Nicholas Rozelle
Third parties 8
| Organisation | City, country | Duties |
|---|---|---|
| EPL Pathology Archives LLC ORG-100042096
|
Leesburg, United States | Other |
| Chillibean Limited ORG-100042592
|
London, United Kingdom | Other |
| SGS France ORG-100011566
|
St Benoit, France | Other |
| Icon Clinical Research Limited ORG-100008322
|
Dublin 18, Ireland | On site monitoring, Code 12, Other, Code 2, Code 8 |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | Data management, E-data capture |
| Eresearchtechnology Inc. ORG-100013039
|
Maryland Heights, United States | Other |
| Labconnect LLC ORG-100042800
|
Johnson City, United States | Other |
| Scout Clinical ORG-100042228
|
Dallas, United States | Other |
Locations
3 EU/EEA countries · 6 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruitment ended | 4 | 2 |
| France | Ongoing, recruitment ended | 3 | 1 |
| Italy | Ongoing, recruitment ended | 15 | 3 |
| Rest of world
United Kingdom, Australia, Canada, Japan, Taiwan, United States
|
— | 109 | — |
Investigational sites
Centre Hospitalier Regional De La Citadelle
University Department of Neuropediatrics, Boulevard Du Douzieme De Ligne 1, 4000, Liege
Universitair Ziekenhuis Gent
Pediatric Neurology department, Corneel Heymanslaan 10, 9000, Gent
Association Institut De Myologie
Research center for pediatric neuromuscular diseases, Porte 20 2eme Etage, 26 Avenue Du Docteur Arnold Netter, Paris
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Paediatric Neurology and Psychiatry Unit, Largo Francesco Vito 1, 00168, Rome
IRCCS Foundation Istituto Neurologico Carlo Besta
Developmental Neurology Unit, Via Giovanni Celoria 11, 20133, Milan
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Neural Stem Cell Laboratory, DEPT Neuroscience Section, Via Francesco Sforza 35, 20122, Milan
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2020-06-16 | 2020-06-22 | 2021-06-02 | ||
| France | 2020-11-17 | 2020-12-17 | 2021-09-16 | ||
| Italy | 2020-07-06 | 2020-07-10 | 2021-12-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 10 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2024-513086-39-00_redacted | 8.0 |
| Protocol (for publication) | D1_Protocol_2024-513086-39-00_redacted_ | 7.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513086-39-00 | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513086-39-00_Dutch | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513086-39-00_French | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513086-39-00_German | 2.0 |
| Synopsis of the protocol (for publication) | D1_Lay Protocol Summary_2024-513086-39-00_Italian | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-513086-39-00_French_redacted | 8.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-513086-39-00_Italian_redacted | 8.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_2024-513086-39-00_redacted | 8.0 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-24 | Italy | Acceptable 2024-06-26
|
2024-06-26 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-14 | Italy | Acceptable 2024-06-26
|
2025-02-14 |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-09-05 | Italy | Acceptable 2025-12-15
|
2025-12-18 |