Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab-ONYX

Study Overview
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Brief Summary
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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 Type 3 SMA who have completed TOPAZ or SAPPHIRE.

Official Title
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An Open-Label, Multicenter, Extension Trial to Evaluate the Long-Term Safety and Efficacy of Apitegromab in Patients With Type 2 and Type 3 Spinal Muscular Atrophy Who Completed Previous Investigational Trials of Apitegromab

Conditions
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Spinal Muscular Atrophy, Spinal Muscular Atrophy Type 3, Spinal Muscular Atrophy Type II, SMA, Neuromuscular Diseases, Muscular Atrophy, Atrophy, Muscular Atrophy, Spinal, Neuromuscular Manifestations, Anti-myostatin

Intervention / Treatment
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* Drug: Apitegromab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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) Estimated life expectancy >2 years from Baseline (Day 1) 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 Able to adhere to the requirements of the protocol, including travel to the trial site and completing all trial procedures and trial visits Females of childbearing potential must have a negative pregnancy test at Baseline and agree to use at least 1 acceptable method of contraception throughout the trial and for 20 weeks after the last dose of apitegromab Exclusion Criteria: Patient permanently discontinued study treatment during the feeder trial (i.e., TOPAZ or SAPPHIRE) Nutritional status that was not stable over the past 6 months and is not anticipated to be stable throughout the trial or medical necessity for a gastric/nasogastric feeding tube, where the majority of feeds are given by this route, as assessed by the Investigator Patient is currently enrolled in any investigational drug trial other than TOPAZ or SAPPHIRE Prior history of severe hypersensitivity reaction or intolerance to SMN-targeted therapies Prior history of severe hypersensitivity reaction or intolerance to apitegromab 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 Any acute or comorbid condition interfering with the well-being of the patient at the patient's last visit in TOPAZ or SAPPHIRE, (including active systemic infection, the need for acute treatment, or inpatient observation due to any reason). After resolution of the condition, the patient can be enrolled in the trial if they meet all the other eligibility criteria. Pregnant or breastfeeding Any other condition or clinically significant laboratory result or ECG value that, in the opinion of the Investigator, may compromise safety or compliance, would preclude the patient from successful completion of the trial, or interfere with the interpretation of the results

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label Extension Study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Period<br>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 | Drug: Apitegromab<br>* Apitegromab (SRK-015) is an investigational, fully human immunoglobulin G4 monoclonal antibody that specifically binds to human proforms (i.e., inactive precursor forms) of myostatin, pro- and latent- myostatin, with high affinity, inhibiting activation of myostatin, a negative regulator of muscle growth and strength.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA | Incidence of TEAEs and SAEs by severity | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points | Hammersmith Functional Motor Scale Expanded (HFMSE) total score at prespecified time points (excludes ambulatory patients) | Up to 6 years | 
| Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points | Revised Upper Limb Module (RULM) total score at prespecified time points (excludes ambulatory patients) | Up to 6 years | 
| Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points | Number of World Health Organization (WHO) motor development milestones attained at prespecified time points (excludes ambulatory patients) | Up to 6 years | 
| Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points | Revised Hammersmith Scale (RHS) total score | Up to 6 years | 
| Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points | Results for 6-Minute Walk Test | Up to 6 years | 
| Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points | 30-Second Sit-to-Stand | Up to 6 years | 
| Further evaluate the immunogenicity of apitegromab | Presence or absence of antidrug antibody (ADA) against apitegromab in serum from blood samples | Up to 6 years |