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

NCT05386680 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: COAV101B12302
• Study Type: interventional
• Target: 27
• Locations: 9 countries
• Sites: 13

Brief Summary

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).

Conditions

Spinal Muscular Atrophy

Keywords

Zolgensma; OAV101; AVXS 101; gene therapy; Muscle atrophy; SBMA; spinal and bulbar muscular atrophy; spinal muscular atrophy; bulbar muscular atrophy; muscle function; myopathy; muscle wasting; atrophied muscle; loss of muscle strength; SMA

Outcome Measures

Primary Outcomes (3)

• Overview of Treatment-emergent Adverse Events by Age Subgroup

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.

  Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.

• Treatment-emergent Adverse Events Related to Treatment by System Organ Class, Preferred Term, Age Subgroup (>= 10%)

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments.

  Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.

• Adverse Events of Special Interest by System Organ Class, Preferred Term, Age Subgroup

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. The occurrence of AEs must be sought by non-directive questioning of the participant at each visit during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination findings, laboratory test findings, or other assessments. An adverse event of special interest (AESI) is primarily defined by using standard Medical Dictionary for Regulatory Activities (MedDRA) queries, and identified as follows: Hepatotoxicity, Transient thrombocytopenia, Thrombotic microangiopathy, Cardiac adverse events, signs and symptoms that may be suggestive dorsal root ganglia toxicity, and new malignancies.

  Adverse events were reported from single dose of study treatment plus 52 weeks, up to a maximum time period of 52 weeks.

Secondary Outcomes (6)

• Change From Baseline at Week 52 Visit in the HFMSE Total Score - Mean (SD)

  Baseline, Week 52

• Change From Baseline at Week 52 Visit in the HFMSE Total Score - LS Means

  Baseline, Week 52

• Change From Baseline at Week 52 Visit in the RULM Total Score - Mean (SD)

  Baseline, Week 52

• Change From Baseline at Week 52 Visit in the RULM Total Score - LS Means

  Baseline, Week 52

• Change From Baseline at Week 52 Visit in Assessment of Caregiver Experience in ACEND Instrument Score - Mean (SD)

  Baseline, Week 52

Study Arms (1)

OAV-101

EXPERIMENTAL

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

Genetic: OAV101

Interventions

OAV101 GENETIC

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

Also known as: AVXS-101, Zolgensma

OAV-101

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (13)

Boston Childrens Hospital

Boston, Massachusetts, 02215, United States

Location

Child Hosp Of The Kings Daughters

Norfolk, Virginia, 23507, United States

Location

University of Wisconsin Madison Medical School

Madison, Wisconsin, 53792-7375, United States

Location

Novartis Investigative Site

Parkville, Victoria, 3052, Australia

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

Location

Novartis Investigative Site

Bron, 69677, France

Location

Novartis Investigative Site

Toulouse, 31059, France

Location

Novartis Investigative Site

Roma, RM, 00168, Italy

Location

Novartis Investigative Site

Kurume, Fukuoka, 830-0011, Japan

Location

Novartis Investigative Site

Shinjuku Ku, Tokyo, 162 8666, Japan

Location

Novartis Investigative Site

Utrecht, 3584, Netherlands

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Publications (1)

• 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. 2026 Feb;32(2):488-493. doi: 10.1038/s41591-025-04119-2. Epub 2025 Dec 8.

  PMID: 41360995 DERIVED

Related Links

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

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Muscular Atrophy; Bulbo-Spinal Atrophy, X-Linked; Muscular Diseases

Interventions

Zolgensma

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Heredodegenerative Disorders, Nervous System; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Musculoskeletal Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: May 23, 2022
• Study Start: January 12, 2023
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: January 13, 2026
• Results First Posted: June 3, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

IT (1); CA (1); BE (1); ES (1); AU (1); NL (1); US (3); JP (2); FR (2)