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

• ClinicalTrials.gov Identifier: NCT05626855
• Recruitment Status: Active, not recruiting
• First Posted: November 25, 2022
• Last Update Posted: May 6, 2024
• Sponsor: Scholar Rock, Inc.
• Information provided by (Responsible Party): Scholar Rock, Inc.

Tracking Information

• First Submitted Date: November 7, 2022
• First Posted Date: November 25, 2022
• Last Update Posted Date: May 6, 2024
• Actual Study Start Date: April 17, 2023
• Estimated Primary Completion Date: November 1, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2022)

Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA [ Time Frame: Up to 6 years ]

Incidence of TEAEs and SAEs by severity

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 15, 2022)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: November 15, 2022)

• Further characterize the PK of apitegromab [ Time Frame: Up to 6 years ]
  Apitegromab concentrations in serum from blood samples at prespecified time points
• Further evaluate the pharmacodynamic (PD) effects of apitegromab [ Time Frame: Up to 6 years ]
  Circulating latent myostatin concentrations in blood samples at prespecified time points
• To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior [ Time Frame: Up to 6 years ]
  Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) at prespecified time points
• To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior [ Time Frame: Up to 6 years ]
  Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue Questionnaire at prespecified time points
• To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior [ Time Frame: Up to 6 years ]
  Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) at prespecified time points
• To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior [ Time Frame: Up to 6 years ]
  Columbia-Suicide Severity Rating Scale (C-SSRS) at prespecified time points

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Long-Term Safety & Efficacy of Apitegromab in Patients With SMA Who Completed Previous Trials of Apitegromab-ONYX
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Open Label Extension Study

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• 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

Drug: Apitegromab

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.

Study Arms

Experimental: Treatment Period

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

Intervention: Drug: Apitegromab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 15, 2022): 260
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2027
• Estimated Primary Completion Date: November 1, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05626855
• Other Study ID Numbers: SRK-015-004
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Scholar Rock, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Scholar Rock, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Scholar Rock, Inc.
• Verification Date: May 2024