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 < 18 years of age with spinal muscular atrophy (SMA) who have discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®)
- Conditions
- motor neuron diseasespinal muscular atrophyWerdnig-Hoffmann disease10029317
- Registration Number
- NL-OMON56088
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 7
* Written informed consent
* SMA diagnosis based on gene mutation analysis with bi-allelic SMN1 mutations
and any copy of SMN2 gene
* Aged 2 < 18 years (screening visit must occur before the patient's 18th
birthday) at time of Screening Visit 1
* Have had at least four loading doses of nusinersen (Spinraza®) or at least 3
months of treatment with risdiplam (Evrysdi®) at Screening
* Must be able to sit independently but must never have taken steps
independently
* Diagnosed through newborn or neonatal screening or patients clinically
diagnosed must have age of clinical symptom onset < 18 months
* Meets age-appropriate institutional criteria for use of anesthesia/sedation
* Female participants who are sexually active or have reached menarche must
have a negative pregnancy test at Screening. Those females who are sexually
active must also agree to use highly effective methods of contraception.
* Excluding SMA, any medical condition considered clinically significant
* Positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis
* Anti Adeno Associated Virus Serotype 9 (AAV9) antibody titer using an
immunoassay is reported as elevated at Screening (reference to >1:50 or a
validated result consistent with being elevated)
* Clinically significant abnormalities in test results during screening period
and/or at Baseline
* Platelet count less than the lower limit of normal (LLN), or platelet
transfusion within 1 month at Screening Visit 1
* Clinically significant abnormal coagulation panel results at Screening
* Hepatic dysfunction (i.e. alanine aminotransferase (ALT), total bilirubin
(TBL), gamma-glutamyl transferase (GGT) or glutamate dehydrogenase (GLDH) >
upper limit of normal (ULN) at Screening (with the exception of isolated AST
elevation: in the absence of other liver laboratory abnormalities, isolated
elevated AST is not considered exclusionary)
* Contraindications for lumbar puncture procedure
* At Baseline (Day-1), participants are excluded if they received:
* nusinersen (Spinraza®) within 4 months at Baseline
* risdiplam (Evrysdi®) within 15 days at Baseline
* 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 the following:
* An active infectious process requiring systemic antiviral or antimicrobial
therapy up to 30 days prior to OAV101 administration, or
* An active but untreated viral or bacterial infectious process up to 30 days
prior to administration of OAV101, or
* Any febrile illness up to 30 days prior to administration of OAV101
* Requiring invasive ventilation, awake noninvasive ventilation for > 6 hours
during a 24-hour period, noninvasive ventilation for >12 hours during a 24-hour
period or requiring tracheostomy, at Screening and up to OAV101 administration
* Concomitant use of any of the following medication categories within 90 days
prior to administration of OAV101
* Ongoing systemic immunosuppressive therapy (e.g., corticosteroids,
cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous
immunoglobulin, rituximab), plasmapheresis, immunomodulators (e.g., adalimumab)
* History of hypersensitivity to any of the study treatments or its excipients
or drugs of similar chemical classes
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To characterize the safety and tolerability of OAV101 IT over a 52-week period<br /><br>in patients with SMA aged 2 to 18 years who have discontinued treatment with<br /><br>nusinersen (Spinraza®) or risdiplam (Evrysdi®):<br /><br>- Number and percentage of participants reporting AEs, related AEs, SAEs, and<br /><br>AESIs</p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess the efficacy of OAV101 IT on motor function, and caregiver impact<br /><br>over a 52-week period in patients with SMA aged 2 to 12 years who have<br /><br>discontinued treatment with nusinersen (Spinraza®) or risdiplam (Evrysdi®):<br /><br>* Change from baseline to Week 52 visit in the HFMSE total score<br /><br>* Change from baseline to Week 52 visit in the RULM total Score<br /><br>* Change from baseline to Week 52 visit in Assessment of Caregiver Experience<br /><br>in ACEND instrument score</p><br>