A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy

Neuromuscular Diseases Clinical Trial

— RESILIENT  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Ambulatory and Non-Ambulatory Participants With Spinal Muscular Atrophy With Open-Label Extension

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05337553
• Other study ID #: BHV2000-301
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 6, 2022
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Biohaven Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial will study the efficacy and safety of taldefgrobep alfa as an adjunctive therapy for participants who are already taking a stable dose of nusinersen or risdiplam or have a history of onasemnogene abeparvovec-xioi, compared to placebo.

Description:

Myostatin is a negative regulator of muscle growth. Blocking myostatin activity has been shown to increase muscle size and function. Taldefgrobep alfa directly blocks myostatin activity and was well tolerated in other clinical studies. In combination with medications that increase the amount of SMN protein in the body, taldefgrobep alfa has the potential to further improve motor function and clinical measures for people living with SMA.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 269
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 21 Years

Eligibility

Key Inclusion Criteria:

• Spinal Muscular Atrophy confirmed by genetic diagnosis of 5q-autosomal recessive SMA as well as SMN2 copy number

• Ambulant or Non-Ambulant

• Treated with an SMA disease-modifying therapy and anticipated to remain on that same treatment regimen and dose throughout the trial including nusinersen, risdiplam, and/or a history of onasemnogene abeparvovec

Key Exclusion Criteria:

• Cannot have previously taken anti-myostatin therapies

• Must weigh at least 15kg

• Respiratory insufficiency, defined by the medical necessity for invasive or non-invasive ventilation for daytime treatment while awake (use overnight or during daytime naps is acceptable)

• History of Spinal Fusion within 6 months of Screening. MAGEC rod nonsurgical adjustments are allowed during the study

• Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Neuromuscular Diseases
• SMA
• Spinal Muscular Atrophy

Intervention

Drug:
• taldefgrobep alfa
DB Phase: 35 mg/50 mg weekly subcutaneous injection
• Placebo
DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
• taldefgrobep alfa
Extension Phase: 35 mg/50 mg weekly subcutaneous injection

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Edegem
Belgium	University Hospital Ghent	Ghent
Belgium	University Hospital Leuven	Leuven
Czechia	University Hospital Brno - Dept. of Pediatric Neurology	Brno
Czechia	Motol University Hospital	Prague
Germany	University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I	Essen
Germany	University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders	Freiburg
Germany	Dr. Von Haunersches Children'S Hospital - Lmu Munich	Munich
Italy	Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital	Bologna
Italy	Nemo-Brescia Clinical Center For Neuromuscular Diseases	Gussago
Italy	IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT	Pavia
Italy	Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience	Roma
Netherlands	University Medical Center Utrecht	Utrecht
Poland	University Clinical Centre in Gdansk - Dept. of Developmental Neurology	Gdansk
Poland	Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic	Poznan
Poland	The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology	Warsaw
Poland	T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.	Wroclaw
Spain	Donostia University Hospital	Donostia
Spain	Hospital Sant Joan de Déu	Esplugues De Llobregat
Spain	Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit	Málaga
Spain	La Fe University and Polytechnic Hospital	Valencia
United Kingdom	Royal Hospital For Children	Glasgow	Scotland
United Kingdom	John Radcliffe Hospital	Oxford
United States	Rare Disease Research	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	UT Pediatric Neurosciences/Dell Children's Medical Center	Austin	Texas
United States	Boston Children's Hospital - Harvard	Boston	Massachusetts
United States	University of Virginia Children's Hospital	Charlottesville	Virginia
United States	Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Neurology Rare Disease Center	Denton	Texas
United States	Duke University Medicine	Durham	North Carolina
United States	University of Kansas Medical Center	Fairway	Kansas
United States	Cook Children's Hospital	Fort Worth	Texas
United States	UF Health, Shands Hospital	Gainesville	Florida
United States	BSHS Office of Research	Grand Rapids	Michigan
United States	Penn State College of Medicine	Hershey	Pennsylvania
United States	Indiana University -Riley Research	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	UCSD & Rady Children's	La Jolla	California
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	CHOP Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's	Phoenix	Arizona
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	UCSF Benioff Children's Hospital, Medical Center	San Francisco	California
United States	Stony Brook University Hospital	Stony Brook	New York
United States	MultiCare Institute of Research and Innovation	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Biohaven Pharmaceuticals, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score	Change in MFM-32 total score from baseline to Week 48. Scores range from 0-3 on each item. The higher the score, indicates higher functioning.	Baseline to Week 48