Long-Term Apitegromab for Spinal Muscular Atrophy

(ONYX Trial)

Not currently recruiting at 75 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called apitegromab for individuals with Spinal Muscular Atrophy (SMA) Types 2 and 3. The goal is to determine the long-term safety and effectiveness of this treatment. Participants will receive an IV infusion of the drug every four weeks for up to 104 weeks. This trial is open to those who have completed earlier trials, specifically the TOPAZ or SAPPHIRE studies, and can travel for visits and treatments. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

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.

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

Research has shown that apitegromab is generally safe and well-tolerated in people with type 2 and type 3 spinal muscular atrophy (SMA). One study found that apitegromab improved motor function, enhancing movement abilities. The same study showed that most participants handled the treatment without major problems. Another study confirmed these results, noting that apitegromab was safe across different ages and doses.

While any treatment can have side effects, current evidence suggests that apitegromab is a safe option for those with SMA. Concerns should be discussed with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Apitegromab is unique because it targets a protein called myostatin, which is involved in inhibiting muscle growth. Unlike standard treatments for Spinal Muscular Atrophy (SMA) that primarily focus on increasing survival motor neuron (SMN) protein levels, such as nusinersen and risdiplam, apitegromab aims to enhance muscle strength directly. This novel approach could potentially improve motor function in people with SMA, offering a complementary benefit to existing therapies. Researchers are excited about apitegromab because it opens up a new avenue for improving quality of life for patients with Type 2 and Type 3 SMA.

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

Research has shown that Apitegromab helps individuals with Type 2 and Type 3 spinal muscular atrophy (SMA) improve their mobility. Several studies have found that patients taking Apitegromab experienced noticeable improvements in movement. In one study, participants who received Apitegromab scored higher in movement assessments than those who did not. The medication was generally safe and caused few serious side effects. These findings suggest that Apitegromab could be a beneficial treatment for individuals with SMA. Participants in this trial will receive Apitegromab 20 mg/kg every 4 weeks by intravenous (IV) infusion during the 104-week Treatment Period. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11299114/

Long-term efficacy, safety, and patient-reported outcomes ... Treatment with apitegromab was associated with both an improved motor function in patients with Type 2 or 3 spinal muscular atrophy (SMA) and with a favorable ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40818473/

a phase 3, double-blind, randomised, placebo-controlled trial Interpretation: Participants in the apitegromab treatment groups (combined 20 mg/kg and 10 mg/kg dose) achieved statistically significant improvements in motor ...

3. neurology.org neurology.org/doi/10.1212/WNL.0000000000209151

Safety and Efficacy of Apitegromab in Patients With Spinal ... Apitegromab led to improved motor function in participants with later-onset types 2 and 3 SMA. These results support a randomized, placebo-controlled phase 3 ...

4. investors.scholarrock.com investors.scholarrock.com/news-releases/news-release-details/pivotal-sapphire-trial-data-published-lancet-neurology

Pivotal SAPPHIRE Trial Data Published in The Lancet ... The data showed that children and adults with SMA had improved motor function with apitegromab—as measured by the gold-standard Hammersmith Functional Motor ...

5. mdaconference.org mdaconference.org/abstract-library/efficacy-and-safety-of-apitegromab-in-individuals-with-type-2-and-type-3-spinal-muscular-atrophy-evaluated-in-the-phase-3-sapphire-trial/

Efficacy and safety of apitegromab in individuals with type ... Apitegromab provided significant improvement in motor function across ages and doses and was generally safe and well-tolerated.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38330285/

Safety and Efficacy of Apitegromab in Patients With Spinal ... This study provides Class III evidence that apitegromab improves motor function in later-onset types 2 and 3 spinal muscular atrophy.

7. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(25)00225-X/abstract

Safety and efficacy of apitegromab in nonambulatory type 2 ... We aimed to assess the safety and efficacy of apitegromab in patients with nonambulatory type 2 or type 3 spinal muscular atrophy receiving nusinersen or ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05626855

Long-Term Safety & Efficacy of Apitegromab in Patients ... The ONYX study is an Open-Label, Multicenter, Extension study that will evaluate the long-term safety and efficacy of Apitegromab in Patients with Type 2 and ...