OAV101 for SMA

(STRENGTH Trial)

Recruiting at 15 trial locations

Overseen By Novartis Gene Therapies Med Info (Europe, Middle East, Africa, Asia-Pacific)

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Nusinersen, Risdiplam

Disqualifiers: Elevated AAV9 antibodies, Invasive ventilation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 day

27 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a gene therapy given as an injection into the lower back in children who haven't used certain other treatments. The therapy works by using a virus to deliver a healthy gene to their cells.

Will I have to stop taking my current medications?

The trial requires that participants stop taking nusinersen (Spinraza®) or risdiplam (Evrysdi®) within a certain timeframe before starting the treatment.

What data supports the effectiveness of the treatment OAV101 for SMA?

Research shows that Onasemnogene Abeparvovec, a gene replacement therapy, significantly improves survival and motor skills in children with spinal muscular atrophy (SMA). It also reduces the need for respiratory and nutritional support, making it an effective treatment for SMA. ^{1 2 3 4 5}

What is known about the safety of OAV101 (Onasemnogene abeparvovec) for SMA?

Onasemnogene abeparvovec, also known as OAV101, has been used as a gene replacement therapy for spinal muscular atrophy (SMA) since 2019. Studies have shown it to be generally safe, though rare side effects have been reported. ^{1 2 5 6 7}

Eligibility Criteria

This trial is for children aged 2 to 12 with Spinal Muscular Atrophy (SMA) who have previously been treated with nusinersen or risdiplam but stopped. They must show SMA symptoms and not have high antibody levels against AAV9, significant test abnormalities, contraindications for spinal taps, recent vaccinations, hospitalizations for pulmonary events or surgeries planned.

Inclusion Criteria

I have been diagnosed with Spinal Muscular Atrophy (SMA).

I am between 2 and 12 years old.

I show symptoms of spinal muscular atrophy.

Exclusion Criteria

Clinically significant abnormalities in test results during screening

I have not received any vaccinations within the last 2 weeks.

I was hospitalized for lung problems or needed nutritional support recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 45 days

1 visit (in-person)

Treatment

Participants receive a single dose of OAV101 by lumbar intrathecal injection and undergo in-patient safety monitoring for at least 48 hours

1 day

1 visit (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

Multiple visits as per Assessment Schedule

Long-term follow-up

Participants are invited to enroll in a Novartis-sponsored long-term follow-up study to monitor long-term safety and efficacy

Treatment Details

Interventions

• OAV101

Trial Overview The study tests OAV101's safety and effectiveness in treating SMA when given through a spinal injection. It involves one treatment day followed by a year of follow-up. Participants are divided into two age groups: 2-5 years old and 6-12 years old.

Participant Groups

Group I: OAV-101 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a real-world study of 64 patients treated with onasemnogene abeparvovec (OA) for spinal muscular atrophy (SMA), those treated at 6-23 months of age achieved higher motor milestones, such as 100% sitting without support and 58.8% walking with assistance, compared to non-treated patients.

OA-treated patients experienced fewer hospitalizations and surgeries, with none requiring tracheostomy or prolonged use of breathing support, indicating a potential improvement in overall health outcomes and caregiver quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey. Toro, W., Yang, M., Georgieva, M., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Real-Life Outcome After Gene Replacement Therapy for Spinal Muscular Atrophy: A Multicenter Experience. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Patient and Caregiver Outcomes After Onasemnogene Abeparvovec Treatment: Findings from the Cure SMA 2021 Membership Survey. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Expert recommendations and clinical considerations in the use of onasemnogene abeparvovec gene therapy for spinal muscular atrophy. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Treatment of spinal muscular atrophy with Onasemnogene Abeparvovec in Switzerland: a prospective observational case series study. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

An overview of the Cure SMA membership database: Highlights of key demographic and clinical characteristics of SMA members. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of olesoxime in patients with type 2 or non-ambulatory type 3 spinal muscular atrophy: a randomised, double-blind, placebo-controlled phase 2 trial. [2019]