Clinical trial NCT05156320: Efficacy and Safety of Apitegromab in Patients With Later-Onset Spinal Muscular Atrophy Treated With Nusinersen or Risdiplam
Official title: Phase 3, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Apitegromab (SRK-015) in Patients With Later-Onset Spinal Muscular Atrophy Receiving Background Nusinersen or Risdiplam Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Muscular Atrophy
Spinal Muscular Atrophy Type 3
Spinal Muscular Atrophy Type 2
SMA
Neuromuscular Diseases
Muscular Atrophy
Atrophy
Muscular Atrophy, Spinal
Neuromuscular Manifestations
Anti-myostatin
Lead sponsor: Scholar Rock, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-14
Enrollment: 188
Sex: ALL
Minimum age (years): 2
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase 3 trial (Study SRK-015-003) was conducted in patients ≥2 years old at Screening, who were previously diagnosed with later-onset spinal muscular atrophy (SMA) (i.e., Type 2 and Type 3 SMA) and were receiving an approved survival motor neuron (SMN) upregulator therapy (i.e., either nusinersen or risdiplam), to confirm the efficacy and safety of apitegromab as an adjunctive therapy to nusinersen and evaluate the efficacy and safety of apitegromab as an adjunctive therapy to risdiplam.


Eligibility criteria: Inclusion Criteria:

* Males and females 2 through 21 years old at Screening.
* Documented diagnosis of 5q SMA.
* Diagnosed with later-onset SMA (i.e., Type 2 and Type 3 SMA) before receiving an approved SMN upregulator therapy (i.e., either nusinersen or risdiplam).
* Must be Nonambulatory at Screening. Nonambulatory patients must be able to sit independently (sits up straight with head erect for at least 10 seconds; does not use arms or hands to balance body or support position) per World Health Organization (WHO) motor milestones definition at Screening.
* Receiving one background therapy for SMA (i.e., either nusinersen or risdiplam) for the time period specified below and anticipated to remain on that same treatment throughout the trial:

  1. If receiving the SMN upregulator therapy nusinersen, must have completed at least 10 months of dosing (i.e., completed the loading regimen and at least 2 maintenance doses) before Screening;
  2. If receiving the SMN upregulator therapy risdiplam, must have completed at least 6 months of dosing before Screening.
* Motor Function Score (HFMSE) ≥10 and ≤45 at Screening.
* Have no physical limitations that would prevent the patient from undergoing motor function outcome measures throughout the duration of the study.
* Able to receive study drug infusions and provide blood samples through the use of a peripheral intravenous (IV) or a long-term IV access device that the patient has placed for reasons independent from the study throughout the duration of the study.
* Able to adhere to the requirements of the protocol, including travel to the study center and completing all study procedures and study visits.
* For patients who are expected to have reached reproductive maturity by the end of the study, adhere to study specific contraception requirements.

Exclusion Criteria:

* Received ZOLGENSMA® (onasemnogene abeparvovec-xioi) at any time and previous treatment with apitegromab.
* Use of invasive ventilation and tracheostomy.
* Use of chronic daytime non-invasive ventilatory support for \>16 hours daily in the 2 weeks prior to dosing, or anticipated to regularly receive such daytime ventilator support chronically over the duration of the study.
* Any acute or co-morbid condition interfering with the well-being of the patient within 7 days of screening, including active systemic infection, the need for acute treatment or inpatient observation due to any reason.
* Severe scoliosis and/or contractures at screening. Based on clinical judgement, any scoliosis or contractures present must be stable over the past 6 months, anticipated to be stable for the duration of the study and not prevent the patient from being evaluated on any functional outcome measures throughout the duration of the study.
* Pregnant or breastfeeding.
* Major orthopedic or other interventional procedure, including spine or hip surgery, considered to have the potential to substantially limit the ability of the patient to be evaluated on any functional outcome measures, within 6 months prior to Screening, or anticipated for the duration of the study.
* Prior history of a hypersensitivity reaction to a monoclonal antibody (mAb) or recombinant protein bearing an Fc domain (such as a soluble receptor-Fc fusion protein), apitegromab, or excipients of apitegromab.
* Treatment with investigational drugs within 3 months prior to Screening.
* Use of therapies with potentially significant muscle effects (such as androgens, insulin-like growth factor, growth hormone, systemic beta-agonist, botulinum toxin, or muscle relaxants or muscle-enhancing supplements) or potentially significant neuromuscular effects (such as acetylcholinesterase inhibitors) within 60 days prior to screening.
* Nutritional status not stable over the past 6 months and not anticipated to be stable throughout the duration of the study.
* Patient has any other condition, which in the opinion of the Investigator may compromise safety or compliance, would preclude the patient from successful completion of the study, or interfere with the interpretation of the results.

Primary outcomes:
measure: Main Efficacy Population: Change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) total score.
timeFrame: Baseline up to 12 months.
Secondary outcomes:
measure: Main Efficacy Population: Change from Baseline in Revised Upper Limb Module (RULM) total score.
timeFrame: Baseline up to 12 months.
measure: Main Efficacy Population: Proportion of patients with ≥3-point change from Baseline in Hammersmith Functional Motor Scale Expanded (HFMSE) total score.
timeFrame: Baseline up to 12 months.
measure: Main Efficacy Population: Change from Baseline in number of WHO motor development milestones attained at 12 months.
timeFrame: Baseline up to 12 months.
measure: Main Efficacy Population and Exploratory Subpopulation combined: Incidence of Treatment Emergent Adverse Events (TEAEs) and Severe Adverse Events (SAEs) by severity.
timeFrame: Baseline up to 12 months.
measure: Main Efficacy Population and Exploratory Subpopulation combined: Apitegromab concentrations in serum from blood samples.
timeFrame: Baseline up to 12 months.
measure: Main Efficacy Population and Exploratory Subpopulation combined: Circulating latent myostatin concentrations in blood samples.
timeFrame: Baseline up to 12 months.
measure: Main Efficacy Population and Exploratory Subpopulation combined: Presence or absence of ADA against apitegromab in serum from blood samples.
timeFrame: Baseline up to 12 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Rady's Children's Hospital/UCSD
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: The Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Helen DeVos Children's Hospital
state: Michigan
city: Saint Paul
country: United States
facility: Gillette Children's Specialty Healthcare
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University, SMA Clinical Research Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liège
country: Belgium
facility: Chr de La Citadelle
city: Lille
country: France
facility: CHU Lille - Hôpital Jeanne de Flandre
city: Paris
country: France
facility: Hôpital Armand Trousseau, I-Motion
city: Toulouse
country: France
facility: CHU Toulouse - Hopital des Enfants
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Munich
country: Germany
facility: Dr. von Haunersches Kinderspital
city: Genoa
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Messina
country: Italy
facility: A.O.U Policlinico G. Martino
city: Milan
country: Italy
facility: Foundation I.R.C.C.S. Carlo Besta Neurological Institute
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Roma
country: Italy
facility: Centro Clinico Nemo Pediatrico Policlinico A. Gemelli-Università Cattolica Sacro Cuore
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne w Gdańsku
city: Poznań
country: Poland
facility: Uniwersytet Medyczny im. Karola Marcinkowskiego w Poznaniu
city: Warsaw
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka: CZD Warszawa
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
References: