Long-term Follow-up with Onasemnogene Abeparvovec-xioi for Spinal Muscular Atrophy

Not currently recruiting at 34 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Gene Therapies

Disqualifiers: Parent unwilling to participate

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: Unknown

Duration: Varies based on parent study

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on assessing the long-term safety and effectiveness of onasemnogene abeparvovec-xioi, a gene therapy for spinal muscular atrophy (SMA), a condition that progressively weakens muscles. Researchers aim to evaluate the ongoing efficacy and safety of the treatment for participants who received it in earlier studies. This study targets individuals with SMA who have previously received onasemnogene abeparvovec-xioi in a past clinical trial and are willing to continue with follow-up appointments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of this treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Studies have shown that onasemnogene abeparvovec-xioi is generally safe for people with spinal muscular atrophy (SMA). Research indicates that administering this treatment intravenously is safe for children weighing between 8.5 to 21 kg. Real-world data supports these findings, showing that many patients tolerate the treatment well.

For those considering the spinal form of onasemnogene abeparvovec-xioi, research suggests it is also safe. Novartis shared positive safety results across a wide range of patients. Another study found it well-tolerated in patients who cannot walk yet but can sit.

Overall, various studies have reported both intravenous and spinal administration of the treatment as safe. These findings provide confidence in the safety of onasemnogene abeparvovec-xioi for people with SMA. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for spinal muscular atrophy?

Unlike the standard treatments for Spinal Muscular Atrophy (SMA) that often focus on slowing disease progression, Onasemnogene Abeparvovec-xioi offers a groundbreaking approach by delivering a functional copy of the SMN1 gene directly to patients. This gene therapy is unique because it aims to address the underlying genetic cause of SMA with a one-time administration. Researchers are particularly excited about its potential to provide long-term benefits with a single dose, which could significantly improve quality of life for patients and reduce the burden of ongoing treatments.

What is the effectiveness track record for onasemnogene abeparvovec-xioi in treating spinal muscular atrophy?

Research has shown that onasemnogene abeparvovec-xioi effectively treats spinal muscular atrophy (SMA). In this trial, participants will receive onasemnogene abeparvovec-xioi either through an IV or directly into the spinal fluid (intrathecal). Studies indicate that patients receiving the IV version often had better survival rates and improved motor skills compared to past data. The intrathecal version also demonstrated promising safety and motor function improvements in children. Overall, both methods of administering onasemnogene abeparvovec-xioi have shown meaningful benefits for people with SMA. ^{1 2 6 7 8}

Who Is on the Research Team?

Sitra Tauscher-Wisniewski, MD

Principal Investigator

Novartis Gene Therapies, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with Spinal Muscular Atrophy who previously received the gene therapy onasemnogene abeparvovec-xioi in a Novartis-sponsored study. Participants or their guardians must consent to and follow the study's procedures.

Inclusion Criteria

I have SMA and was treated with onasemnogene abeparvovec-xioi in a Novartis study.

Participant/parent/legal guardian willing and able to complete the informed consent process and comply with study procedures and visit schedule

I have SMA and was treated with onasemnogene abeparvovec-xioi in a Novartis study.

Exclusion Criteria

Parent/legal guardian unable or unwilling to participate in the long-term follow-up safety study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants received treatment with IV or IT onasemnogene abeparvovec-xioi in their respective parent study

Varies based on parent study

Long-term Follow-up

Continuous monitoring of safety, efficacy, and durability of response to onasemnogene abeparvovec-xioi treatment

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Onasemnogene Abeparvovec-xioi

Trial Overview The long-term safety and effectiveness of onasemnogene abeparvovec-xioi, a gene replacement therapy for SMA, are being monitored as participants transition from earlier trials for ongoing evaluation.

How Is the Trial Designed?

Group I: Intravenous (IV) & Intrathecal (IT) Onasemnogene Abeparvovec-xioi Experimental Treatment 1 Intervention

Participants received treatment with IV onasemnogene abeparvovec-xioi in an onasemnogene abeparvovec-xioi or received treatment with IT onasemnogene abeparvovec-xioi in an onasemnogene.

Who Is Running the Clinical Trial?

Novartis Gene Therapies

Lead Sponsor

Trials

9

Recruited

45,200+

Published Research Related to This Trial

Onasemnogene abeparvovec (OA) demonstrated significant efficacy in improving motor function in infants with Spinal Muscular Atrophy across a wide age range (22 days to 72 months) and weight range (3.2 to 17 kg), with notable improvements seen as early as 3 months in patients treated before 24 months of age.

The study identified that older age at treatment was a predictor of elevated transaminase levels, indicating a higher risk of liver-related side effects, which should be considered when selecting patients for OA therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec in spinal muscular atrophy: predictors of efficacy and safety in naïve patients with spinal muscular atrophy and following switch from other therapies. Pane, M., Berti, B., Capasso, A., et al.[2023]

In a study of 21 infants with spinal muscular atrophy (SMA) treated with onasemnogene abeparvovec, 76% achieved at least one World Health Organization motor milestone, indicating significant efficacy in improving motor function.

All children experienced transient side effects, with vomiting being universal and moderate to severe transaminitis occurring more frequently in infants weighing 8 kg or more, highlighting the importance of monitoring and individualized management for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. D'Silva, AM., Holland, S., Kariyawasam, D., et al.[2022]

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]

Onasemnogene abeparvovec, the first approved gene-replacement therapy for spinal muscular atrophy, has been shown to have manageable safety risks, with 101 out of 102 patients experiencing at least one treatment-emergent adverse event (AE) during clinical trials.

Key safety concerns include hepatotoxicity, which resolved with treatment, and transient decreases in platelet counts, while thrombotic microangiopathy (TMA) was noted in postmarketing data, indicating the need for monitoring and potential medical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy. Day, JW., Mendell, JR., Mercuri, E., et al.[2022]

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 ... Novartis announced positive safety and efficacy results from the Phase III program for investigational intrathecal onasemnogene abeparvovec (OAV101 IT)

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03381729

NCT03381729 | Study of Intrathecal Administration ... The purpose of this trial is to evaluate the safety and tolerability of intrathecal administration of onasemnogene abeparvovec-xioi in infants and children ...

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

Real-World Outcomes in Patients with Spinal Muscular ... We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting.

4. curesma.org curesma.org/novartis-intrathecal-gene-therapy-topline-results-december2024/

Novartis Intrathecal Gene Therapy Onasemnogene ... This pivotal study assessed the efficacy and safety of investigational intrathecal onasemnogene abeparvovec (OAV101 IT) in treatment-naïve patients with spinal ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10974574/

Real-World Safety Data of the Orphan Drug ... Real-World Safety Data of the Orphan Drug Onasemnogene Abeparvovec (Zolgensma®) for the SMA Rare Disease: A Pharmacovigilance Study Based on the ...

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

Positive Safety and Efficacy Data for Intrathecal ... It is similar to Zolgensma (onasemnogene abeparvovec) but is administered intrathecally to significantly reduce the dosage needed.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10200150/

Intrathecal Onasemnogene Abeparvovec for Sitting ... STRONG (NCT03381729) assessed the safety/tolerability and efficacy of intrathecal onasemnogene abeparvovec for sitting, nonambulatory SMA patients.