Apitegromab for Spinal Muscular Atrophy

(OPAL Trial)

Recruiting at 3 trial locations

Overseen By Scholar Rock

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Scholar Rock, Inc.

Must be taking: SMN1-targeted, SMN2-targeted

Disqualifiers: Severe scoliosis, Severe contractures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

Duration: 48 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called apitegromab for infants with spinal muscular atrophy (SMA), a condition affecting muscle strength and movement. The goal is to assess the safety and effectiveness of apitegromab when combined with existing SMA therapies. Babies under 2 years old with SMA who experience delays in reaching motor milestones might be suitable candidates. Participants will receive apitegromab through an IV every four weeks for about a year. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important advancements in SMA care.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it requires that participants are already being treated with an approved SMA therapy like nusinersen or risdiplam.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that apitegromab is generally safe and well-tolerated in people with spinal muscular atrophy (SMA). Studies have found that it helps improve movement abilities. Importantly, these studies report that most patients did not experience serious side effects, indicating a good safety record.

While specific side effects are not detailed, the consistent safety findings across different studies suggest that apitegromab is unlikely to cause major harm. Additionally, ongoing studies testing this treatment in children under two years old imply reasonable safety based on past research. Always consult healthcare professionals to understand how this information applies personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for spinal muscular atrophy (SMA), which primarily focus on enhancing or replacing the SMN1 or SMN2 gene, Apitegromab offers a new approach by targeting myostatin, a protein that normally limits muscle growth. Researchers are excited about Apitegromab because it has the potential to significantly boost muscle strength and function, which could be a game-changer for individuals with SMA. By being administered alongside existing SMN-targeted therapies, Apitegromab could complement these treatments, leading to better overall outcomes for patients.

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

Research has shown that apitegromab may enhance movement abilities in people with spinal muscular atrophy (SMA), particularly those with types 2 and 3. Studies have consistently found that patients taking apitegromab demonstrated better motor skills. The Hammersmith Functional Motor Scale, a standard tool for assessing movement in SMA, measured these improvements. Additionally, apitegromab has generally been safe and well-tolerated across various ages and doses. In this trial, participants will receive either a low or high dose of apitegromab combined with SMN therapy. These findings suggest that apitegromab could effectively support motor development in individuals with SMA. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for children under 2 years old with a confirmed diagnosis of Spinal Muscular Atrophy (SMA) who have delayed motor milestones. They must weigh at least as much as the lowest 1% of kids their age and have been treated or are being treated with approved SMA therapies like nusinersen or risdiplam.

Inclusion Criteria

My child has delayed motor skills due to SMA, or scored less than 55 on the CHOP-INTEND.

I have been treated with or am currently on SMN-targeted therapy.

My child's weight is at or above the 1st percentile for their age.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period

48 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Apitegromab

Trial Overview The study tests Apitegromab's effects on young children with SMA, alongside other treatments like Risdiplam and Nusinersen. It aims to understand how well Apitegromab works, its safety, and if it's tolerable in these patients through a double-blind Phase 2 trial.

How Is the Trial Designed?

Group I: Apitegromab low dose + SMN Therapy Experimental Treatment 3 Interventions

Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).

Group II: Apitegromab high dose + SMN Therapy Experimental Treatment 3 Interventions

Patients who are less than 2 years of age with SMA will receive apitegromab every 4 weeks by intravenous (IV) infusion during the 48-week Treatment Period. Patients must have been treated with an approved SMN1-targeted therapy (ie, onasemnogene abeparvovec-xioi) or are continuing to be treated with an approved SMN2-targeted therapy (ie, nusinersen or risdiplam).

Who Is Running the Clinical Trial?

Scholar Rock, Inc.

Lead Sponsor

Trials

7

Recruited

710+

Citations

1. 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 ...

2. 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.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05156320

NCT05156320 | Efficacy and Safety of Apitegromab in ... Safety and efficacy of apitegromab in nonambulatory type 2 or type 3 spinal muscular atrophy (SAPPHIRE): a phase 3, double-blind, randomised, placebo ...

4. 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 ...

5. 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 ...

6. investors.scholarrock.com investors.scholarrock.com/news-releases/news-release-details/scholar-rock-presents-new-phase-3-sapphire-data-2025-muscular

Scholar Rock Presents New Phase 3 SAPPHIRE Data at ... A greater proportion of patients treated with apitegromab had improvements of ≥3 points in their HFMSE scores compared to placebo with odds ...