Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
173
Countries
6
Sites
9
Spinal Muscular Atrophy
The primary objective of this study is to assess long-term safety in terms of treatment-emergent serious adverse events (SAEs) and treatment-emergent adverse events of special interest (AESIs) throughout the duration of the study. The primary clinical question of interest is: What is the long term effect on safety of O…
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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Trial duration
- 5 Jan 2023 → ongoing
- Decision date (initial)
- 2024-08-08
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- Yes
- Funding sources
- Novartis Pharma AG
External identifiers
- EU CT number
- 2024-511707-42-00
- EudraCT number
- 2021-006781-21
- ClinicalTrials.gov
- NCT05335876
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others, Safety, Efficacy
The primary objective of this study is to assess long-term safety in terms of treatment-emergent serious adverse events (SAEs) and treatment-emergent adverse events of special interest (AESIs) throughout the duration of the study. The primary clinical question of interest is: What is the long term effect on safety of OAV101 for patients with SMA who were treated with OAV101 by IV or IT administration?
Secondary objectives 1
- The secondary objectives of this study are to assess long-term 1) safety for measures other than adverse events and for clinically significant vital sign and laboratory values and 2) efficacy as measured using the Developmental Milestone Checklist, Hammersmith Functional Motor Scale – Expanded (HFMSE) and Revised Upper Limb Module (RULM)
Conditions and MedDRA coding
Spinal Muscular Atrophy
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | PT | 10041582 | Spinal muscular atrophy | 100000004850 |
Regulatory references
- Plan to share IPD
- Yes
| EU CT number | Title | Sponsor |
|---|---|---|
| 2021-003474-31 | 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 ≥ 2 to < 18 years of age, treatment naive, sitting, and never ambulatory, Μία τυχαιοποιημένη, διπλά τυφλή μελέτη με ομάδα εικονικής παρέμβασης με σκοπό την αξιολόγηση της αποτελεσματικότητας και της ασφάλειας του ενδορραχιαία (ΕΡ) χορηγούμενου OAV101 σε ασθενείς με όψιμη έναρξη νωτιαίας μυικής ατροφίας τύπου 2, ηλικίας ≥ 2 έως < 18 ετών, οι οποίοι δεν έχουν λάβει θεραπεία, είναι ικανοί να παραμείνουν σε καθιστή θέση και δεν υπήρξαν ποτέ περιπατητικοί | |
| 2020-005995-37 | A Phase lllb, open-label, single-arm, single-dose, multicenter study to evaluate the safety, tolerability and efficacy of gene replacement therapy with intravenous OAV101 (AVXS-101) in pediatric patients with spinal muscular atrophy (SMA), Estudio de fase IIIb, multicéntrico, abierto, con una única dosis y un único grupo para evaluar la seguridad, la tolerabilidad y la eficacia de la terapia de sustitución génica con OAV101 (AVXS-101) por vía intravenosa en pacientes pediátricos con atrofia muscular espinal (AME)., Etude de phase IIIb, multicentrique, en ouvert, à un seul bras, évaluant la sécurité d’emploi, la tolérance, et l’efficacité d’une dose unique de thérapie génique par OAV101 (AVXS-101), administrée par voie intraveineuse, chez des patients pédiatriques atteints d’amyotrophie spinale, Studio di fase IIIB, in aperto, a braccio singolo, a dose singola, multicentrico per valutare la sicurezza, tollerabilità ed efficacia della terapia di sostituzione genica con OAV 101 (AVXS-101) per via endovenosa in pazienti pediatrici con atrofia muscolare spinale (SMA) | |
| 2021-006709-31 | Phase IIIb, open-label, single-arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101 administered intrathecally (1.2 x 1014 vector genomes) to participants 2 to 12 years of age with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®), Estudio de fase IIIb, multicéntrico, abierto y de un único grupo en el que se evalúan la seguridad, la tolerabilidad y la eficacia de OAV101 administrado intratecalmente (1,2 x 1014 genomas vectoriales) a participantes de 2 a 12 años de edad con atrofia muscular espinal (AME) que hayan discontinuado el tratamiento con nusinersen (Spinraza®) o risdiplam (Evrysdi®)., Etude de phase IIIb, multicentrique, en ouvert, à un seul bras, évaluant la sécurité d'emploi, la tolérance et l'efficacité d’une dose unique de thérapie génique par OAV101 administré par voie intrathécale (1,2 x 1014 génomes du vecteur) à des patients âgés de 2 à 12 ans atteints d'amyotrophie spinale (SMA) ayant arrêté le traitement par nusinersen (Spinraza®) ou risdiplam (Evrysdi®), Studio di Fase IIIb, in aperto, a braccio singolo, multicentrico per valutare la sicurezza, la tollerabilità e l’efficacia di OAV101, somministrato per via intratecale (1,2 x 1014 genomi vettoriali) a partecipanti di età compresa tra 2 e 12 anni con atrofia muscolare spinale (SMA) che hanno sospeso il trattamento con nusinersen (Spinraza®) o risdiplam (Evrysdi®) |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Participated in an OAV101 clinical trial.
- Written informed consent must be obtained before any assessment is performed.
- Patient/Parent/legal guardian willing and able to comply with study procedures.
Exclusion criteria 1
- There are no specific exclusion criteria for this study.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Number and proportion of patients reporting treatment-emergent serious adverse events (SAEs) by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) and Preferred Term (PT) for the entire duration of the study (i.e., up to 5 years)
- Number and proportion of patients reporting treatment-emergent adverse events of special interest (AESIs) by AESI category and MedDRA SOC and PT within each AESI category for the entire duration of the study (i.e., up to 5 years)
Secondary endpoints 6
- The number and proportion of participants demonstrating each developmental milestone according to the Developmental Milestone Checklist
- The number and proportion of participants demonstrating maintenance of each developmental milestone
- Change from Baseline in the Hammersmith Functional Motor Scale – Expanded (HFMSE) total score
- Change from Baseline in the Revised Upper Limb Module (RULM) total score
- Number and proportion of patients with potentially clinically significant vital sign findings, summarized individually for each vital sign parameter
- Number and proportion of patients with potentially clinically significant laboratory values, summarized individually for each laboratory parameter
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PRD11525179 · Product
- Active substance
- Onasemnogene Abeparvovec
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRATHECAL USE
- Max daily dose
- 0.0 Other
- Max total dose
- 0.0 Other
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- NOVARTIS PHARMA AG
- Paediatric formulation
- Yes
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/028/15
Zolgensma 2 × 10^13 vector genomes/mL solution for infusion
PRD8079948 · Product
- Active substance
- Onasemnogene Abeparvovec
- Substance synonyms
- AVXS-101, 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
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 0.0 Other
- Max total dose
- 0.0 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
- Yes
- Orphan designation
- Yes
- Orphan designation number
- EMA/OD/028/15
- 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
- Novartis Pharma Arzneimittel GmbH
Public contact point
- Organisation
- Novartis Pharma AG
- Contact name
- Novartis Pharma Arzneimittel GmbH
Third parties 11
| Organisation | City, country | Duties |
|---|---|---|
| ProtaGene CGT GmbH ORG-100041450
|
Heidelberg, Germany | Laboratory analysis |
| Q Squared Solutions Holdings LLC ORG-100043288
|
Valencia, United States | Laboratory analysis |
| Transperfect Translations International Inc. ORG-100043494
|
New York, United States | Other |
| Labcorp Early Development Laboratories Inc. ORG-100012865
|
Indianapolis, United States | Laboratory analysis |
| Greenphire LLC ORG-100041621
|
King Of Prussia, United States | Other |
| Q Squared Solutions Limited ORG-100042527
|
Livingston, United Kingdom | Laboratory analysis |
| Bioagilytix Labs LLC ORG-100013030
|
Durham, United States | Laboratory analysis |
| Ancillare LP ORG-100044089
|
Horsham, United States | Other |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | On site monitoring, Code 10, Code 11, Code 12, Other, Code 5, Data management, E-data capture, Code 8 |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | Other |
| SGS France ORG-100011566
|
St Benoit, France | Laboratory analysis |
Locations
6 EU/EEA countries · 9 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruitment ended | 4 | 1 |
| Denmark | Ongoing, recruitment ended | 3 | 1 |
| France | Ongoing, recruitment ended | 7 | 4 |
| Italy | Ongoing, recruitment ended | 3 | 1 |
| Netherlands | Ongoing, recruitment ended | 6 | 1 |
| Spain | Ongoing, recruitment ended | 3 | 1 |
| Rest of world
Thailand, South Africa, China, Japan, Canada, Malaysia, Saudi Arabia, Vietnam, India, Australia, Brazil, Singapore, United Kingdom, Taiwan, United States, Mexico
|
— | 147 | — |
Investigational sites
Rigshospitalet
1701: Hematology, Blegdamsvej 9, 2100, Copenhagen Oe
Raymond-Poincare Hospital
1901: Unité Neuromusculaire, Département de Neurologie pédiatrique et Unité de Soins Intensifs, 104 Boulevard Raymond Poincare, 92380, Garches
Hopital Des Enfants
1904: Neurologie pédiatrique, 330 Avenue De Grande Bretagne, 31059, Toulouse Cedex 9
Les Hopitaux Universitaires De Strasbourg
1902: Département de Pédiatrie, 1 Avenue Moliere, Bp 49, Strasbourg Cedex 2
Hospital Femme Mere Enfant
1903: Service MPR pédiatrique L'Escale, 52 Boulevard Pinel, 69500, Bron
Universita Cattolica Del Sacro Cuore
2201: Pediatric neurology, Largo Agostino Gemelli 8, 00168, Rome
Universitair Medisch Centrum Utrecht
2601: Sylvia Toth Centrum, Heidelberglaan 100, 3584 CX, Utrecht
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 | 2023-01-05 | 2023-01-05 | 2024-10-01 | ||
| Denmark | 2024-05-30 | 2024-05-30 | 2024-11-15 | ||
| France | 2023-05-23 | 2023-05-23 | 2025-01-29 | ||
| Italy | 2023-02-09 | 2023-02-09 | 2024-10-03 | ||
| Netherlands | 2024-09-11 | 2024-09-11 | 2025-01-28 | ||
| Spain | 2024-03-11 | 2024-03-11 | 2024-11-11 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 59 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol - Signature Page_2024-511707-42-00_1_English_Red | 4 |
| Protocol (for publication) | D1_Protocol_2024-511707-42-00_1_English_Red | 4 |
| Recruitment arrangements (for publication) | K1_BEL Recruitment Procedure Description English COAV101A12308 Public | 1.0 |
| Recruitment arrangements (for publication) | K1_DNK Recruitment arrangements Filenote COAV101A12308 | NA |
| Recruitment arrangements (for publication) | K1_ESP Recruitment Procedure Description English COAV101A12308 Public | 1.0 |
| Recruitment arrangements (for publication) | K1_FRA Recruitment Procedure Description French COAV101A12308 Public | V 1.0 |
| Recruitment arrangements (for publication) | K1_ITA Recruitment arrangement Filenote COAV101A12308 | NA |
| Recruitment arrangements (for publication) | K1_NLD Recruitment Procedure Description English COAV101A12308 Public | 1.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Assent Child 12-17 Dutch COAV101A12308 Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Assent Child 12-17 French COAV101A12308 Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Assent Child 7-11 Dutch COAV101A12308 Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Assent Child 7-11 French COAV101A12308 Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Caregiver Child Dutch COAV101A12308 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Caregiver Child French COAV101A12308 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main Dutch COAV101A12308 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Main French COAV101A12308 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Other Female partner Dutch COAV101A12308 Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Other Female partner French COAV101A12308 Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Other Preg participant Dutch COAV101A12308 Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Other Preg participant French COAV101A12308 Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Other Pregnant partner Dutch COAV101A12308 Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_BEL Country ICF Other Pregnant partner French COAV101A12308 Public | 3.0 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Assent Child 12-14 years Danish COAV101A12308 Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Assent Child 15-17 Years Danish COAV101A12308 Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Caregiver Adult Danish COAV101A12308 Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Main Adult Danish COAV101A12308 Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Other Adult Female Partner Info Danish COAV101A12308 Public | 2.1 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Other Adult Pregnant Subject Danish COAV101A12308 Public | v2.0 |
| Subject information and informed consent form (for publication) | L1_DNK Country ICF Other Pregnant Partner Danish COAV101A12308 Public | v2.0 |
| Subject information and informed consent form (for publication) | L1_ESP Country ICF Assent Spanish COAV101A12308 Public | 4.0 |
| Subject information and informed consent form (for publication) | L1_ESP Country ICF Information sheet for female partner Spanish COAV101A12308 Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_ESP Country ICF Main Spanish COAV101A12308 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_ESP Country ICF Parent Legal Gardian Spanish COAV101A12308 Public | 5.0 |
| Subject information and informed consent form (for publication) | L1_ESP Country ICF Pregnant Participant COAV101A12308 Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_ESP Country ICF Pregnant Patner COAV101A12308 Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_FRA Country ICF Assent Assent 7-11 y old French COAV101A12308 Public | V 3.0 |
| Subject information and informed consent form (for publication) | L1_FRA Country ICF Assent Assent 12-17 y old French COAV101A12308 Public | V 4.0 |
| Subject information and informed consent form (for publication) | L1_FRA Country ICF Caregiver French COAV101A12308 Public | V 5.0 |
| Subject information and informed consent form (for publication) | L1_FRA Country ICF Main French COAV101A12308 Public | V 5.0 |
| Subject information and informed consent form (for publication) | L1_ITA Country ICF Adolescent Assent Italian COAV101A12308 Public | 4.06 |
| Subject information and informed consent form (for publication) | L1_ITA Country ICF Child Assent Italian COAV101A12308 Public | 4.05 |
| Subject information and informed consent form (for publication) | L1_ITA Country ICF Main Italian COAV101A12308 Public | 4.07 |
| Subject information and informed consent form (for publication) | L1_ITA Country ICF Main Parent Italian COAV101A12308 Public | 4.07 |
| Subject information and informed consent form (for publication) | L1_ITA Country ICF Other Female Partner information Italian COAV101A12308 public | 4.03 |
| Subject information and informed consent form (for publication) | L1_ITA Country IRB-IEC Additional-Amendment Approval Italian COAV101A12308 Public | NA |
| Subject information and informed consent form (for publication) | L1_ITA_Country ICF Other ITA_Pregnancy_FU_Participants Italian COAV101A12308 Public | 4.03 |
| Subject information and informed consent form (for publication) | L1_ITA_Country ICF Other ITA_Pregnancy_FU_Partner Italian COAV101A12308 Public | 4.03 |
| Subject information and informed consent form (for publication) | L1_NLD Country ICF Assent till 12 Dutch COAV101A12308 Public | 3.1 |
| Subject information and informed consent form (for publication) | L1_NLD Country ICF Assent 12-16 Dutch COAV101A12308 Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_NLD Country ICF Caregiver Child Dutch COAV101A12308 Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_NLD Country ICF Main Dutch COAV101A12308 Public | 4.1 |
| Subject information and informed consent form (for publication) | L1_NLD Country ICF Other Pregnant partner Dutch COAV101A12308 Public | 2.0 |
| Subject information and informed consent form (for publication) | L1_NLD Country ICF Other Pregnant subject Dutch COAV101A12308 Public | 2.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2024-511707-42-00_1_Dutch_Red | 0 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2024-511707-42-00_1_English_Red | 0 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2024-511707-42-00_1_French_Red | 0 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2024-511707-42-00_1_German_Red | 0 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2024-511707-42-00_1_Italian_Red | 0 |
| Synopsis of the protocol (for publication) | D1_Protocol Summary in Lay Language_2024-511707-42-00_1_Spanish_Red | 0 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-10 | Denmark | Acceptable 2024-08-07
|
2024-08-08 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-11-22 | Denmark | Acceptable 2025-03-10
|
2025-03-10 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2025-04-17 | Denmark | Acceptable 2025-05-28
|
2025-05-28 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-12-19 | Denmark | Acceptable 2026-03-30
|
2026-03-30 |