OAV101 for SMA

(STRENGTH Trial)

No longer recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called OAV101 for individuals with spinal muscular atrophy (SMA), a condition that progressively weakens muscles. The researchers aim to determine if OAV101 is safe and effective for those who have previously tried treatments like nusinersen or risdiplam. They seek children and teens, ages 2 to under 18, who have been managing SMA and have received specific doses of these prior treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that OAV101 is likely to be safe for humans?

Research has shown that OAV101, a gene therapy for spinal muscular atrophy (SMA), was safe in earlier studies. Researchers closely monitored recipients of OAV101, and the results were promising. Most patients tolerated the treatment well, with no serious side effects reported. These findings suggest that OAV101 is generally safe for people with SMA, based on past trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for SMA?

OAV101 is unique because it offers a new approach for treating spinal muscular atrophy (SMA) through gene therapy. Unlike traditional treatments like Spinraza or Evrysdi, which require repeated dosing, OAV101 is administered as a one-time intrathecal injection. This treatment delivers a high dose of vector genomes directly into the central nervous system, potentially providing long-lasting effects by addressing the genetic root of SMA. Researchers are excited about OAV101 because it represents a significant shift towards more sustainable and less invasive treatment options for patients with SMA.

What evidence suggests that OAV101 might be an effective treatment for SMA?

Research has shown that OAV101, also known as onasemnogene abeparvovec, holds promise for treating spinal muscular atrophy (SMA). In one study, patients improved by 2.39 points on a motor skills scale. Real-world evidence supports these findings, indicating the treatment's effectiveness for many SMA patients. Although some serious side effects have been reported, most patients experienced improved health outcomes with the treatment. These findings suggest that OAV101 could be a helpful option for those with SMA, especially after discontinuing treatments like nusinersen or risdiplam. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. novartis.com novartis.com/news/media-releases/new-novartis-phase-iii-data-demonstrate-meaningful-efficacy-and-safety-results-intrathecal-onasemnogene-abeparvovec-broad-patient-population-sma

New Novartis Phase III data demonstrate meaningful ... Treatment with investigational OAV101 IT led to statistically significant 2.39-point improvement on the HFMSE vs.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38250783/

Real-World Outcomes in Patients with Spinal Muscular ... These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient ...

3. nature.com nature.com/articles/s41434-025-00535-8

Fatal outcomes following onasemnogene abeparvovec in ... This investigation assessed clinical effectiveness and adverse effects of OA in a cohort including advanced SMA, and compared to historical survival data.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04851873

Study Details | NCT04851873 | Safety and Efficacy of ... This was an open-label, single arm, multi-center study designed to evaluate the safety, tolerability and efficacy of OAV101 in participants with SMA who weigh ...

5. jpccr.eu jpccr.eu/pdf-193633-119783?filename=Clinical%20outcomes%20of.pdf

Clinical outcomes of Onasemnogene Abeparvovec use in ... The drug significantly enhances key clinical outcomes and is relatively safe to use, with only a few serious adverse effects attributed to the ...

6. checkrare.com checkrare.com/positive-safety-and-efficacy-data-for-intrathecal-administration-of-gene-therapy-for-sma/

Positive Safety and Efficacy Data for Intrathecal ... Norman Putzki, MD, Novartis, discusses positive safety and efficacy data for OAV101 IT, an investigational gene therapy for SMA.

7. curesma.org curesma.org/wp-content/uploads/2021/08/Novartis-IT-Clinical-hold-lift-and-STEER-announcement-community-statement-US-1.pdf

Community Statement from Novartis Gene Therapies ZOLGENSMA is a prescription gene therapy used to treat children less than 2 years old with spinal muscular atrophy (SMA). ZOLGENSMA is given as a one-time ...

8. clinicaltrial.be clinicaltrial.be/en/details/37798?per_page=20&only_recruiting=0&enrolling_by_invitation=1&active_not_recruiting=1&completed=0&only_eligible=0&only_active=0

Efficacy and Safety of Intrathecal OAV101 (AVXS-101) in P... This is a multi-center, randomized, sham-controlled, double-blind study to investigate the safety, tolerability, and efficacy of IT OAV101 in ...