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

Sponsor

Scholar Rock, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05626855

Collaborator

(none)

260

Enrollment

Locations

Arm

44.3

Anticipated Duration (Months)

9.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Apitegromab	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Open Label Extension StudyOpen Label Extension Study

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Apr 24, 2023

Anticipated Primary Completion Date :

Nov 1, 2026

Anticipated Study Completion Date :

Jan 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
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	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.

Arm

Intervention/Treatment

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

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.

Outcome Measures

Primary Outcome Measures

Evaluate the long-term safety and tolerability of apitegromab in patients with Type 2 and Type 3 SMA [Up to 6 years]
Incidence of TEAEs and SAEs by severity

Secondary Outcome Measures

Evaluate the long-term efficacy of apitegromab by assessing changes in motor function outcome measures at prespecified time points [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 [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 [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 [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 [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 [Up to 6 years]
30-Second Sit-to-Stand
Further evaluate the immunogenicity of apitegromab [Up to 6 years]
Presence or absence of antidrug antibody (ADA) against apitegromab in serum from blood samples

Other Outcome Measures

Further characterize the PK of apitegromab [Up to 6 years]
Apitegromab concentrations in serum from blood samples at prespecified time points
Further evaluate the pharmacodynamic (PD) effects of apitegromab [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 [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 [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 [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 [Up to 6 years]
Columbia-Suicide Severity Rating Scale (C-SSRS) at prespecified time points

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	Stanford University Medical Center	Palo Alto	California	United States	94304
3	Rady's Children's Hospital/UCSD	San Diego	California	United States	92123
4	Children's Hospital Colorado	Aurora	Colorado	United States	80045
5	Nemours Children's Hospital	Orlando	Florida	United States	32827
6	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
7	University of Iowa	Iowa City	Iowa	United States	52242
8	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
9	Boston Children's Hospital	Boston	Massachusetts	United States	02115
10	Helen DeVos Children's Hospital	Grand Rapids	Michigan	United States	49503
11	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota	United States	55101
12	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110
13	Columbia University, SMA Clinical Research Center	New York	New York	United States	10032
14	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina	United States	27157
15	Oregon Health & Sciences University	Portland	Oregon	United States	97239
16	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
17	University of Utah	Salt Lake City	Utah	United States	84112
18	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
19	Seattle Children's Hospital	Seattle	Washington	United States	98105
20	UZ Gent	Gent		Belgium	9000
21	UZ Leuven	Leuven		Belgium	3000
22	Chr de La Citadelle	Liège		Belgium	4000
23	Centro Clinico Nemo Pediatrico Policlinico A. Gemelli-Università Cattolica Sacro Cuore	Roma		Italy	00168
24	Universitair Medisch Centrum Utrecht	Utrecht		Netherlands	3584
25	Instytut Pomnik - Centrum Zdrowia Dziecka: CZD Warszawa	Warsaw		Poland	04-736
26	Hospital Sant Joan de Déu	Barcelona		Spain
27	Hospital Universitario y Politécnico La Fe	Valencia		Spain