What side effects are associated with this type of intervention?

Common treatments for Spinal Muscular Atrophy (SMA) include nusinersen, risdiplam, and onasemnogene abeparvovec. Nusinersen can cause side effects such as respiratory infections, constipation, and back pain. Risdiplam may lead to fever, diarrhea, and rash. Onasemnogene abeparvovec, a gene therapy, can result in liver enzyme elevations, vomiting, and thrombocytopenia. For myostatin inhibitors like Apitegromab, potential side effects observed in similar treatments include muscle spasms, fatigue, and injection site reactions. It is important to discuss these with a healthcare provider to understand the risks and benefits.

What prior FDA approvals exist?

The FDA has approved several treatments for Spinal Muscular Atrophy (SMA), including nusinersen (Spinraza), a disease-modifying therapy that increases SMN protein production, and onasemnogene abeparvovec (Zolgensma), a gene replacement therapy that delivers a functional copy of the SMN1 gene. These treatments have shown significant clinical benefits in SMA patients. Apitegromab, currently under investigation, is a myostatin inhibitor aimed at improving muscle strength and function, representing a novel approach compared to existing therapies.

What other types of research exist?

Promising novel alternatives to Apitegromab for SMA patients include gene therapy with onasemnogene abeparvovec (Zolgensma), which targets the underlying genetic cause of SMA by delivering a functional copy of the SMN1 gene. Another alternative is risdiplam (Evrysdi), an oral medication that increases SMN protein production by modifying SMN2 gene splicing. Both treatments have shown significant efficacy in clinical trials and are approved for use in SMA patients.

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Monoclonal Antibodies

Long-Term Apitegromab for Spinal Muscular Atrophy (ONYX Trial)

Phase 3

Waitlist Available

Research Sponsored by Scholar Rock, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients have completed the Phase 2 TOPAZ (Study SRK-015-002) trial or the Phase 3 SAPPHIRE (Study SRK-015-003) trial (For TOPAZ, completed is defined as completion of Visit EC14 in Extension Period C or participating in TOPAZ at the time the trial is ended. For SAPPHIRE, completed is defined as completion of Visit 14 or participating in SAPPHIRE at the time the trial is ended)

Able to receive study drug infusions and provide blood samples through the use of a peripheral IV or a long-term IV access device that the patient has placed for reasons independent from the trial

Must not have

Use of chronic daytime noninvasive ventilatory support for >16 hours daily in the 2 weeks before dosing, or anticipated to regularly receive such daytime ventilator support chronically throughout the trial

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 6 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While specific side effects aren't listed here, common ones may include reactions at the infusion site, potential allergic responses if there's a history of hypersensitivity to similar treatments, and general drug-related adverse effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I can receive medication through an IV and give blood samples.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I use a ventilator during the day for more than 16 hours.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 6 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 6 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 6 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA

Secondary study objectives

Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points

Further evaluate the immunogenicity of apitegromab

Other study objectives

Further characterize the PK of apitegromab

Further evaluate the pharmacodynamic (PD) effects of apitegromab

To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment PeriodExperimental Treatment1 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

0 / 3Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Spinal Muscular Atrophy (SMA) include Nusinersen, Risdiplam, and gene therapy with Onasemnogene abeparvovec. Nusinersen and Risdiplam work by modifying the splicing of the SMN2 gene to increase the production of functional SMN protein, which is deficient in SMA patients. Onasemnogene abeparvovec delivers a functional copy of the SMN1 gene to motor neurons via a viral vector, addressing the root cause of the disease. Myostatin inhibition, as studied in the trial Apitegromab, aims to promote muscle growth and strength by blocking myostatin, a protein that inhibits muscle development. This is particularly important for SMA patients, as increased muscle mass and strength can significantly improve their motor function and quality of life.

Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches.[Myostatin blockade therapy for muscular atrophy].