Safety and Efficacy of Intravenous OAV101 (AVXS-101) in Pediatric Patients With Spinal Muscular Atrophy (SMA)

Phase 1

• Conditions: Spinal Muscular Atrophy; MedDRA version: 20.1Level: PTClassification code 10041582Term: Spinal muscular atrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2020-005995-37-IT
• Lead Sponsor: OVARTIS PHARMA AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-08-17
• Last Update Posted: 13 December 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Written informed consent/assent obtained prior to any assessment performed
2. Symptomatic SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and any copy of SMN2 gene.
3. Weight = 8.5 kg and = 21 kg at the time of Screening Visit 2
4. Naive to treatment or have discontinued an approved drug/therapy
5. Up-to date on recommended childhood vaccinations and RSV prophylaxis with palivizumab (also known as Synagis), per local standard of care
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Participants meeting any of the following criteria are not eligible for inclusion in this study.
1. Previous OAV101 use or previous use of any AAV9 gene therapy
2. BMI < 3rd percentile based on WHO Child Growth Standard
3. Participant with history of aspiration pneumonia or signs of aspiration (eg, coughing or sputtering of food) within 4 weeks prior to screening
4. Anti-AAV9 antibody titer > 1:50 as determined by ligand binding immunoassay at the time of screening
5. History of gene therapy, hematopoietic transplantation, or solid organ transplantation
6. Inability to take corticosteroids
7. Concomitant use of immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months prior to gene replacement therapy (eg, cyclosporine, tacrolimus, methotrexate, rituximab cyclophosphamide, IV immunoglobulin)
8. Requiring invasive ventilation, tracheostomy or awake non-invasive ventilation (standard of care nocturnal BiPAP is not considered exclusionary)
9. Administration of vaccines 2 weeks prior to infusion of OAV101
10. Awake hypoxemia (O2 saturation <95%) or awake oxygen saturation level decrease between screening and dosing that is clinically significant, as per investigator judgment.
11. Clinically significant neurologic or neuromuscular conditions other than SMA as determined by the principal Investigator
12. Clinically significant abnormalities in laboratory test results at Screening as determined by the Investigator
13. Hepatic dysfunction (i.e. AST, ALT, bilirubin, GGT or GLDH, = ULN; CTCAE = 1) at Screening (with the exception of isolated AST elevation: in the absence of other liver laboratory abnormalities, isolated AST elevation is not considered exclusionary)
14. Excluding SMA, any medically unstable condition considered clinically significant by the Investigator, including cardiomyopathy, hepatic dysfunction, kidney disorder, endocrine disorder, GI disorders, metabolic disorders, severe respiratory compromise and significant brain abnormalities at either Screening or Baseline that, in the opinion of the investigator, would interfere with the overall interpretation of safety or efficacy of the study
15. Presence of a confirmed or suspected active infectious process from screening and up to dose administration
16. If previously treated with disease modifying therapy, participants are excluded if they received
- less than 3 doses of nusinersen (Spinraza®)
- nusinersen (Spinraza®) within 4 months prior to Screening
- risdiplam (EvrysdiTM) within 15 days prior to Screening (washout period of at least 5 half-lives before Screening)
17. Use of other investigational drugs within 5 half-lives of enrollment/initiation of study treatment (select as appropriate) within 30 days (eg, small molecules) / or until the expected pharmacodynamic effect has returned to baseline (eg, biologics), whichever is longer; or longer if required by local regulations.
18. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
19. Documented any parental consanguinity

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified