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

Primary Purpose

Spinal Muscular Atrophy, Neuromuscular Diseases, SMA

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
taldefgrobep alfa
Placebo
taldefgrobep alfa
Sponsored by
Biohaven Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Spinal Muscular Atrophy

Eligibility Criteria

4 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Phoenix Children's
  • UCSD & Rady Children's
  • Children's Hospital of Los Angeles
  • UCSF Benioff Children's Hospital, Medical Center
  • Children's Hospital Colorado
  • Yale University
  • Children's National Medical Center
  • UF Health, Shands Hospital
  • Rare Disease Research
  • Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana University -Riley Research
  • University of Iowa
  • University of Kansas Medical Center
  • Boston Children's Hospital - Harvard
  • BSHS Office of Research
  • Washington University in St. Louis
  • Columbia University Medical Center
  • Stony Brook University Hospital
  • Duke University Medicine
  • Cincinnati Children's Hospital Medical Center
  • Nationwide Children's Hospital
  • Penn State College of Medicine
  • CHOP Children's Hospital of Philadelphia
  • UPMC Children's Hospital of Pittsburgh
  • Vanderbilt University Medical Center
  • UT Pediatric Neurosciences/Dell Children's Medical Center
  • Neurology Rare Disease Center
  • Cook Children's Hospital
  • Baylor College of Medicine at The Children's Hospital of San Antonio
  • University of Virginia Children's Hospital
  • Children's Hospital of The King's Daughters
  • MultiCare Institute of Research and Innovation
  • Medical College of Wisconsin
  • University Hospital Antwerp
  • University Hospital Ghent
  • University Hospital Leuven
  • Chr Citadella
  • University Hospital Brno - Dept. of Pediatric Neurology
  • Motol University Hospital
  • University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I
  • University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders
  • Dr. Von Haunersches Children'S Hospital - Lmu Munich
  • Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital
  • Nemo-Brescia Clinical Center For Neuromuscular Diseases
  • IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT
  • Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience
  • University Medical Center Utrecht
  • University Clinical Centre in Gdansk - Dept. of Developmental Neurology
  • Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic
  • The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology
  • T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.
  • Donostia University Hospital
  • Hospital Sant Joan de Déu
  • Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit
  • La Fe University and Polytechnic Hospital
  • Royal Hospital For Children
  • Royal Manchester Children'S Hospital
  • John Radcliffe Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

taldefgrobep alfa

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
April 14, 2022
Last Updated
October 4, 2023
Sponsor
Biohaven Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05337553
Brief Title
A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 6, 2022 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biohaven Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spinal Muscular Atrophy, Neuromuscular Diseases, SMA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
269 (Actual)

8. Arms, Groups, and Interventions

Arm Title
taldefgrobep alfa
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
taldefgrobep alfa
Other Intervention Name(s)
BHV-2000, BMS-986089
Intervention Description
DB Phase: 35 mg/50 mg weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
taldefgrobep alfa
Other Intervention Name(s)
BHV-2000, BMS-986089
Intervention Description
Extension Phase: 35 mg/50 mg weekly subcutaneous injection
Primary Outcome Measure Information:
Title
Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score
Description
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.
Time Frame
Baseline to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lindsey Lair, MD
Organizational Affiliation
Biohaven Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Phoenix Children's
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
UCSD & Rady Children's
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
UCSF Benioff Children's Hospital, Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
UF Health, Shands Hospital
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Rare Disease Research
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana University -Riley Research
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
University of Kansas Medical Center
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Facility Name
Boston Children's Hospital - Harvard
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
BSHS Office of Research
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
Washington University in St. Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Stony Brook University Hospital
City
Stony Brook
State/Province
New York
ZIP/Postal Code
11794
Country
United States
Facility Name
Duke University Medicine
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Penn State College of Medicine
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
CHOP Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
UT Pediatric Neurosciences/Dell Children's Medical Center
City
Austin
State/Province
Texas
ZIP/Postal Code
78723
Country
United States
Facility Name
Neurology Rare Disease Center
City
Denton
State/Province
Texas
ZIP/Postal Code
75208
Country
United States
Facility Name
Cook Children's Hospital
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Baylor College of Medicine at The Children's Hospital of San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
89207
Country
United States
Facility Name
University of Virginia Children's Hospital
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Children's Hospital of The King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
MultiCare Institute of Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
University Hospital Antwerp
City
Edegem
ZIP/Postal Code
02650
Country
Belgium
Facility Name
University Hospital Ghent
City
Ghent
ZIP/Postal Code
09000
Country
Belgium
Facility Name
University Hospital Leuven
City
Leuven
ZIP/Postal Code
03000
Country
Belgium
Facility Name
Chr Citadella
City
Liège
ZIP/Postal Code
04000
Country
Belgium
Facility Name
University Hospital Brno - Dept. of Pediatric Neurology
City
Brno
ZIP/Postal Code
625 00
Country
Czechia
Facility Name
Motol University Hospital
City
Prague
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Dr. Von Haunersches Children'S Hospital - Lmu Munich
City
Munich
ZIP/Postal Code
80337
Country
Germany
Facility Name
Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital
City
Bologna
ZIP/Postal Code
40139
Country
Italy
Facility Name
Nemo-Brescia Clinical Center For Neuromuscular Diseases
City
Gussago
ZIP/Postal Code
25064
Country
Italy
Facility Name
IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience
City
Roma
ZIP/Postal Code
00165
Country
Italy
Facility Name
University Medical Center Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
University Clinical Centre in Gdansk - Dept. of Developmental Neurology
City
Gdańsk
ZIP/Postal Code
80-925
Country
Poland
Facility Name
Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic
City
Poznań
ZIP/Postal Code
60-355
Country
Poland
Facility Name
The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology
City
Warsaw
ZIP/Postal Code
04-730
Country
Poland
Facility Name
T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.
City
Wrocław
ZIP/Postal Code
54-049
Country
Poland
Facility Name
Donostia University Hospital
City
Donostia
ZIP/Postal Code
20014
Country
Spain
Facility Name
Hospital Sant Joan de Déu
City
Esplugues De Llobregat
ZIP/Postal Code
08950
Country
Spain
Facility Name
Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit
City
Málaga
ZIP/Postal Code
29011
Country
Spain
Facility Name
La Fe University and Polytechnic Hospital
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Royal Hospital For Children
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G51 4TF
Country
United Kingdom
Facility Name
Royal Manchester Children'S Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
John Radcliffe Hospital
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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