Phase IIIb, Open-label, Multi-center Study to Evaluate Safety, Tolerability and Efficacy of OAV101 Administered Intrathecally to Participants With SMA Who Discontinued Treatment With Nusinersen or Risdiplam

NCT ID: NCT05386680

Last Updated: 2026-01-13

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

27 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-12

Study Completion Date

2024-11-29

Brief Summary

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This was a Phase IIIb open-label, single arm, multi-center study to evaluate the safety, tolerability and efficacy of OAV101B in participants with SMA aged 2 to \<18 years after the discontinuation of treatment with nusinersen or risdiplam. The study aimed to enroll approximately 28 participants across each of 2 age brackets (2 to \<6 years, and 6 to \<18 years).

Detailed Description

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Eligible participants received a single OAV101B administration of 1.2x1014 vector genomes on Day 1 (Treatment period) and were followed for a period of 52 weeks.

Participants were admitted to the hospital on Day -1 for pre-treatment baseline procedures. After receiving OAV101B on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, based on Investigator judgment.

Conditions

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Spinal Muscular Atrophy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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OAV-101

Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose

Group Type EXPERIMENTAL

OAV101

Intervention Type GENETIC

Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose

Interventions

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OAV101

Intrathecal administration of OAV101 at a dose of 1.2 x 10\^14 vector genomes, one time dose

Intervention Type GENETIC

Other Intervention Names

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AVXS-101 Zolgensma

Eligibility Criteria

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Inclusion Criteria

* SMA diagnosis
* Aged 2 to \< 18 years
* Have had at least four loading doses of nusinersen (Spinraza®) or at least 3 months of treatment with risdiplam (Evrysdi®) at Screening
* Must have symptoms of SMA as defined in the protocol

Exclusion Criteria

* Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an immunoassay is reported as elevated
* Clinically significant abnormalities in test results during screening
* Contraindications for lumbar puncture procedure
* At Baseline, participants are excluded if they received:

* nusinersen (Spinraza®) or
* risdiplam (Evrysdi®) within a defined timeframe
* Vaccinations 2 weeks prior to administration of OAV101
* Hospitalization for a pulmonary event, or for nutritional support within 2 months prior to Screening or inpatient major surgery planned.
* Presence of an infection or febrile illness up to 30 days prior to administration of OAV101
* Requiring invasive ventilation
Minimum Eligible Age

2 Years

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Boston Childrens Hospital

Boston, Massachusetts, United States

Site Status

Child Hosp Of The Kings Daughters

Norfolk, Virginia, United States

Site Status

University of Wisconsin Madison Medical School

Madison, Wisconsin, United States

Site Status

Novartis Investigative Site

Parkville, Victoria, Australia

Site Status

Novartis Investigative Site

Leuven, , Belgium

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Bron, , France

Site Status

Novartis Investigative Site

Toulouse, , France

Site Status

Novartis Investigative Site

Roma, RM, Italy

Site Status

Novartis Investigative Site

Kurume, Fukuoka, Japan

Site Status

Novartis Investigative Site

Shinjuku Ku, Tokyo, Japan

Site Status

Novartis Investigative Site

Utrecht, , Netherlands

Site Status

Novartis Investigative Site

Barcelona, Catalonia, Spain

Site Status

Countries

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United States Australia Belgium Canada France Italy Japan Netherlands Spain

References

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Kwon JM, Munell F, Le Goff L, Yuge K, Kato T, Cances C, De Waele L, Woodcock IR, Mercuri EM, Proud CM, Darras BT, Hayes LH, Oskoui M, Visootsak J, Williams G, Ilic A, Yang L, van der Pol WL. Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial. Nat Med. 2025 Dec 8. doi: 10.1038/s41591-025-04119-2. Online ahead of print.

Reference Type DERIVED
PMID: 41360995 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=2618

A Plain Language Trial Summary is available on www.novctrd.com

https://www.novctrd.com/ctrdweb/ppatientsummary/ppatientsummaries?periodicPatientSummaryId=698

A Pediatric Plain Language Trial Summary is available on www.novctrd.com

Other Identifiers

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COAV101B12302

Identifier Type: -

Identifier Source: org_study_id

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