Long-Term Apitegromab for Spinal Muscular Atrophy

(ONYX Trial)

Recruiting at 67 trial locations

Overseen By Paul Miller

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Scholar Rock, Inc.

Must not be taking: SMN-targeted therapies, Apitegromab

Disqualifiers: Unstable nutrition, Ventilator use, 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: 26

Duration: 104 weeks

238 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called Apitegromab to see if it is safe and effective for people with certain types of spinal muscular atrophy (SMA). It focuses on patients who have already participated in previous research. The goal is to see if the medication can help improve their muscle function over time.

Do I have to stop taking my current medications for the trial?

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

How is the drug Apitegromab different from other treatments for spinal muscular atrophy?

Apitegromab is unique because it is a muscle-targeting therapy, unlike other treatments that focus on increasing the levels of the SMN protein. It works by enhancing muscle strength and function, providing a complementary approach to existing therapies that primarily address the genetic cause of spinal muscular atrophy. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for patients with Type 2 or Type 3 Spinal Muscular Atrophy (SMA) who completed the TOPAZ or SAPPHIRE trials. They must be able to receive infusions, travel to the site, and have a life expectancy over two years. Women of childbearing age need a negative pregnancy test and must use contraception.

Inclusion Criteria

I have finished the Phase 2 TOPAZ or Phase 3 SAPPHIRE trial.

I am not pregnant and agree to use birth control during and for 20 weeks after the trial.

Able to adhere to the requirements of the protocol, including travel to the trial site and completing all trial procedures and trial visits

Exclusion Criteria

You had a bad reaction or couldn't tolerate apitegromab before.

I don't have any current health issues that would affect my participation.

Pregnant or breastfeeding

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive apitegromab 20 mg/kg every 4 weeks by intravenous (IV) infusion

104 weeks

26 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

Open-label extension

Evaluate the long-term safety and efficacy of Apitegromab in patients who completed previous trials

Long-term

Treatment Details

Interventions

• Apitegromab

Trial Overview The ONYX study tests the long-term safety and effectiveness of Apitegromab in SMA patients from previous studies. It's an open-label extension study, meaning all participants know they are receiving Apitegromab and are monitored over time.

Participant Groups

Group I: Treatment Period Experimental Treatment 1 Intervention

Patients who are ≥2 years of age with Type 2 and Type 3 SMA will receive apitegromab 20 mg/kg every 4 weeks by intravenous (IV) infusion during the 104-week Treatment Period

Who Is Running the Clinical Trial?

Scholar Rock, Inc.

Lead Sponsor

Trials

7

Recruited

710+

Findings from Research

Infantile-onset spinal muscular atrophy (SMA) is primarily caused by low levels of the Survival Motor Neuron (SMN) protein, which leads to the selective degeneration of spinal motor neurons, although the exact reasons for this selectivity are still unclear.

Recent advances in SMA research have led to the development of promising new therapies that focus on increasing SMN protein levels, marking significant progress in treatment options for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Motor neuron biology and disease: A current perspective on infantile-onset spinal muscular atrophy. Jha, NN., Kim, JK., Monani, UR.[2020]

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 phase 3 trial involving 22 infants with spinal muscular atrophy type 1, 59% achieved independent sitting for 30 seconds or longer by 18 months, compared to 0% in an untreated cohort, demonstrating significant efficacy of the gene therapy onasemnogene abeparvovec.

91% of treated patients survived without the need for permanent ventilation by 14 months, highlighting the therapy's potential to improve survival outcomes compared to only 26% in the untreated group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. Day, JW., Finkel, RS., Chiriboga, CA., et al.[2021]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Motor neuron biology and disease: A current perspective on infantile-onset spinal muscular atrophy. [2020]

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

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy in patients with two copies of SMN2 (STR1VE): an open-label, single-arm, multicentre, phase 3 trial. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Current treatments of spinal muscular atrophy in adults. [2023]

5. England 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. [2023]