OAV101 for Spinal Muscular Atrophy

(STEER Trial)

No longer recruiting at 44 trial locations

Overseen By Novartis Medical Information - International

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: SMN-targeting therapies

Disqualifiers: Elevated AAV9 antibodies, Hepatic dysfunction, Ventilation needs, 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: 6

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 Type 2 spinal muscular atrophy (SMA), a condition affecting muscle strength and movement. The trial aims to assess the safety and effectiveness of this treatment when administered through the spine. Participants will receive either the OAV101 treatment or a sham procedure, which involves no medication. Individuals diagnosed with SMA who have never taken certain medications for it, can sit independently, but have never walked on their own, might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that participants have never used any SMN-targeting therapies, like risdiplam or nusinersen, so if you are currently taking these, you would need to stop. The protocol does not specify about other medications, so it's best to discuss with the trial team.

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

Research shows that OAV101, a treatment for spinal muscular atrophy (SMA), has positive safety results. Researchers closely monitored participants who received OAV101 for about 48 hours after treatment to catch any immediate side effects early.

The findings suggest that patients generally tolerate the treatment well. While side effects can occur with any treatment, the data so far indicates that these are manageable. OAV101 is a type of gene therapy, and similar treatments have already been approved for other conditions, which adds confidence to its safety.

Overall, the research supports that OAV101 is safe for people with Type 2 SMA, making it a promising treatment option. ^{1 2 3 4 5}

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

OAV101 is unique because it offers a one-time intrathecal dose specifically designed for treating Spinal Muscular Atrophy (SMA), a condition often managed with ongoing treatments like Spinraza or Zolgensma. Unlike these treatments, OAV101 delivers a single infusion of vector genomes directly into the spinal fluid, potentially providing long-lasting benefits with just one administration. Researchers are excited about OAV101 because it targets the root cause of SMA by introducing a genetic component that could help produce the missing survival motor neuron (SMN) protein, offering hope for sustained improvement in motor function with minimal dosing.

What evidence suggests that OAV101 might be an effective treatment for spinal muscular atrophy?

Research has shown that OAV101, which participants in this trial may receive, may help treat spinal muscular atrophy (SMA). In one study, patients who received OAV101 improved by 2.39 points on a test measuring motor skills. Another report found that all patients survived without major health issues for one year after treatment. These findings suggest that OAV101 could improve movement and increase survival in people with SMA. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for children aged 2 to <18 with Type 2 spinal muscular atrophy (SMA) who can sit but not walk independently, have had symptoms since ≥6 months old, and haven't used any SMN-targeting therapies. They must pass a motor function test and not have severe contractures, liver issues, recent or planned spine/hip surgery, sensory abnormalities, high AAV9 antibody levels, recent infections or require extensive ventilation.

Inclusion Criteria

My condition is confirmed to be 5q spinal muscular atrophy.

I can sit by myself but have never been able to walk on my own.

I have never taken SMN-targeting therapies like Evrysdi or Spinraza.

Exclusion Criteria

I need a machine to help me breathe, either through a mask for more than 6 hours a day or through a tracheostomy.

You have significant problems with feeling or sensation in your nerves during a medical exam.

My test shows high levels of AAV9 antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6-8 weeks

Treatment Period 1

Participants receive OAV101 or sham procedure with in-patient hospitalization on Study Day 1, Day 2, and Day 3 (optional)

1 week

3 visits (in-patient)

Follow-up Period 1

Participants are monitored for safety and efficacy assessments

52 weeks

Treatment Period 2

Eligible participants receive OAV101 or sham procedure with in-patient hospitalization

1 week

3 visits (in-patient)

Follow-up Period 2

Participants are monitored for safety and efficacy assessments

12 weeks

Long-term follow-up

Participants may enroll in a long-term follow-up study to monitor long-term safety and efficacy

15 years

What Are the Treatments Tested in This Trial?

Interventions

• OAV101
• Sham control

Trial Overview The trial tests the effectiveness of OAV101 given through the spine compared to a sham control in kids with SMA over 15 months. It aims to see if this treatment improves their condition without causing harm.

How Is the Trial Designed?

Group I: OAV101 Experimental Treatment 1 Intervention

OAV101 administered as a single, one-time intrathecal dose of 1.2 x 10\^14 vector genomes (vg).

Group II: Sham control Placebo Group 1 Intervention

A skin prick in the lumbar region without any medication.

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

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 ... In the Phase III STEER study, treatment with OAV101 IT led to a statistically significant 2.39-point improvement on the Hammersmith Functional ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05089656

NCT05089656 | Efficacy and Safety of Intrathecal OAV101 ... A randomized, sham-controlled, double-blind study to evaluate the efficacy and safety of intrathecal OAV101 in type 2 spinal muscular atrophy (SMA) patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10977451/

Real-World Outcomes in Patients with Spinal Muscular ... Event-free survival of 100% was observed for 70 patients with three copies of SMN2 post-treatment at 1 year. Although one patient required ...

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/novartis-positive-phaseiii-data-spinal-muscular-atrophy-therapy

Novartis Shares Positive Phase III Data for Spinal Muscular ... Novartis has announced positive results from its Phase III clinical trial program evaluating intrathecal onasemnogene abeparvovec (OAV101 IT).

5. 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.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04851873

Study Details | NCT04851873 | Safety and Efficacy of ... After receiving OAV101 on Day 1, participants underwent in-patient safety monitoring over the next 48 hours, after which the participant could be discharged, ...

7. 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 ...

8. 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 ...