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

November 6, 2023 updated by: Biohaven Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

269

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Edegem, Belgium, 02650
        • University hospital Antwerp
      • Ghent, Belgium, 09000
        • University Hospital Ghent
      • Leuven, Belgium, 03000
        • University Hospital Leuven
  • Czechia
      • Brno, Czechia, 625 00
        • University Hospital Brno - Dept. of Pediatric Neurology
      • Prague, Czechia, 150 06
        • Motol University Hospital
  • Germany
      • Essen, Germany, 45147
        • University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I
      • Freiburg, Germany, 79106
        • University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders
      • Munich, Germany, 80337
        • Dr. Von Haunersches Children'S Hospital - Lmu Munich
  • Italy
      • Bologna, Italy, 40139
        • Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital
      • Gussago, Italy, 25064
        • Nemo-Brescia Clinical Center For Neuromuscular Diseases
      • Pavia, Italy, 27100
        • IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT
      • Roma, Italy, 00165
        • Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience
  • Netherlands
      • Utrecht, Netherlands, 3584 CX
        • University Medical Center Utrecht
  • Poland
      • Gdańsk, Poland, 80-925
        • University Clinical Centre in Gdansk - Dept. of Developmental Neurology
      • Poznań, Poland, 60-355
        • Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic
      • Warsaw, Poland, 04-730
        • The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology
      • Wrocław, Poland, 54-049
        • T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.
  • Spain
      • Donostia, Spain, 20014
        • Donostia University Hospital
      • Esplugues De Llobregat, Spain, 08950
        • Hospital Sant Joan de Deu
      • Málaga, Spain, 29011
        • Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit
      • Valencia, Spain, 46026
        • La Fe University and Polytechnic Hospital
  • United Kingdom
      • Oxford, United Kingdom, OX3 9DU
        • John Radcliffe Hospital
    • Scotland
      • Glasgow, Scotland, United Kingdom, G51 4TF
        • Royal Hospital For Children
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Phoenix Children's
    • California
      • La Jolla, California, United States, 92037
        • UCSD & Rady Children's
      • Los Angeles, California, United States, 90027
        • Children's Hospital of Los Angeles
      • San Francisco, California, United States, 94158
        • UCSF Benioff Children's Hospital, Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF Health, Shands Hospital
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Rare Disease Research
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University -Riley Research
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Kansas
      • Fairway, Kansas, United States, 66205
        • University of Kansas Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital - Harvard
    • Michigan
      • Grand Rapids, Michigan, United States, 49503
        • BSHS Office of Research
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27705
        • Duke University Medicine
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State College of Medicine
      • Philadelphia, Pennsylvania, United States, 19104
        • CHOP Children's Hospital of Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15224
        • UPMC Children's Hospital of Pittsburgh
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Texas
      • Austin, Texas, United States, 78723
        • UT Pediatric Neurosciences/Dell Children's Medical Center
      • Denton, Texas, United States, 75208
        • Neurology Rare Disease Center
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Hospital
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia Children's Hospital
      • Norfolk, Virginia, United States, 23507
        • Children's Hospital of The King's Daughters
    • Washington
      • Tacoma, Washington, United States, 98405
        • MultiCare Institute of Research and Innovation
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: taldefgrobep alfa

taldefgrobep alfa - Double-blind (DB) Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week DB phase.

taldefgrobep alfa/taldefgrobep alfa - Extension Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week Open label Extension (OLE) phase.
Drug: taldefgrobep alfa
DB Phase: 35 mg/50 mg weekly subcutaneous injection
Other Names:
  • BHV-2000
  • BMS-986089
Drug: taldefgrobep alfa
Extension Phase: 35 mg/50 mg weekly subcutaneous injection
Other Names:
  • BHV-2000
  • BMS-986089
Placebo Comparator: Placebo

Placebo - Double-blind (DB) Phase: Participants receive weight based 35 mg/50 mg weekly subcutaneous injection for 48-week DB phase.

Placebo/taldefgrobep alfa - Extension Phase: Participants who receive placebo during DB phase, receive weight based 35 mg/50 mg weekly subcutaneous taldefgrobep alfa injection for 48-week OLE phase.
Drug: Placebo
DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
Drug: taldefgrobep alfa
DB Phase: 35 mg/50 mg weekly subcutaneous injection
Other Names:
  • BHV-2000
  • BMS-986089
Drug: taldefgrobep alfa
Extension Phase: 35 mg/50 mg weekly subcutaneous injection
Other Names:
  • BHV-2000
  • BMS-986089

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score
Time Frame: Baseline to Week 48
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biohaven Pharmaceuticals, Inc.

Investigators

  • Study Director: Lindsey Lair, MD, Biohaven Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 6, 2022

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

April 14, 2022

First Submitted That Met QC Criteria

April 14, 2022

First Posted (Actual)

April 20, 2022

Study Record Updates

Last Update Posted (Actual)

November 7, 2023

Last Update Submitted That Met QC Criteria

November 6, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BHV2000-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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