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

Neuromuscular Diseases Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05626855
• Other study ID #: SRK-015-004
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 17, 2023
• Est. completion date: January 1, 2027

Study information

• Verified date: May 2024
• Source: Scholar Rock, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 260
• Est. completion date: January 1, 2027
• Est. primary completion date: November 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Neuromuscular Diseases
• Neuromuscular Manifestations
• SMA
• Spinal Muscular Atrophy
• Spinal Muscular Atrophy Type 3
• Spinal Muscular Atrophy Type II

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.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	CHR Citadelle	Liege
France	CHRU de Lille - Hpital Jeanne de Flandre	Lille
France	Hopital Trousseau - I-Motion	Paris
France	CHU Toulouse Hopital des Enfants	Toulouse
Germany	Universitätskinderklinik Bonn, Abteilung für Neuropädiatrie und SPZ	Bonn
Germany	Universitatsklinikum Essen	Essen
Germany	Universitatsklinikum Freiburg	Freiburg
Italy	Carlo Besta Neurological Research Institute	Milano
Italy	NeuroMuscular Omnicentre	Milano
Italy	Fondazione Policlinico Universitario A. Gemelli	Roma
Netherlands	UMC Utrecht	Utrecht
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu, Oddzial Kliniczny Neurologii Dzieci i Mlodziezy	Poznan
Poland	Instytut Pomnik - Centrum Zdrowia Dziecka	Warsaw
Spain	Hospital Sant Joan de Deau	Barcelona
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United Kingdom	Leeds Children's Hospital Clinical Research	Leeds
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Johns HopkinsHospital	Baltimore	Maryland
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Texas Southwestern - Pediatric Neurology	Dallas	Texas
United States	University of Kansas Medical Center	Fairway	Kansas
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	University of Iowa	Iowa City	Iowa
United States	UCSD Altman Clinical and Translational Research	La Jolla	California
United States	University of Wisconsin Hospital	Madison	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Children's Specialty Group PLLC (Children's Hospital of The King's Daughters)	Newport News	Virginia
United States	Nemours Biomedical Research	Orlando	Florida
United States	Stanford Neuroscience Health Center	Palo Alto	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University Medical Campus	Saint Louis	Missouri
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	Seattle Children's Hospital	Seattle	Washington
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Scholar Rock, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Further characterize the PK of apitegromab	Apitegromab concentrations in serum from blood samples at prespecified time points	Up to 6 years
Other	Further evaluate the pharmacodynamic (PD) effects of apitegromab	Circulating latent myostatin concentrations in blood samples at prespecified time points	Up to 6 years
Other	To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior	Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) at prespecified time points	Up to 6 years
Other	To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior	Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue Questionnaire at prespecified time points	Up to 6 years
Other	To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior	Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) at prespecified time points	Up to 6 years
Other	To further evaluate the effect of apitegromab on patient/caregiver-reported disability, fatigability, and suicidal ideation and behavior	Columbia-Suicide Severity Rating Scale (C-SSRS) at prespecified time points	Up to 6 years
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Further evaluate the immunogenicity of apitegromab	Presence or absence of antidrug antibody (ADA) against apitegromab in serum from blood samples	Up to 6 years