Clinical trial NCT05337553: A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Spinal Muscular Atrophy
Neuromuscular Diseases
SMA
Lead sponsor: Biohaven Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2022-04-20
Enrollment: 269
Sex: ALL
Minimum age (years): 4
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 and/or risdiplam and/or have a history of onasemnogene abeparvovec, 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.

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 and/or 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

Primary outcomes:
measure: Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score
timeFrame: Baseline to Week 48
measure: Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS)
timeFrame: Baseline to Week 48
measure: Change from Baseline in lean body mass
timeFrame: Baseline, Week 48
measure: Change from Baseline in bone mineral density
timeFrame: Baseline, Week 48
measure: Change from baseline in Tanner staging
timeFrame: Baseline, Week 48
measure: Injection acceptability assessments
timeFrame: Week 48
measure: Number of Participants with new or worsening lab abnormalities, Adverse Events (AEs), Serious AEs (SAEs) and AEs Leading to Study Drug Discontinuation in the Double-blind Phase
timeFrame: Up to 48 Weeks
measure: Trough plasma concentration
timeFrame: Baseline, Week 12, Week 24, Week 36, Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's
state: Arizona
city: La Jolla
country: United States
facility: UCSD & Rady Children's
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF Benioff Children's Hospital, Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: UF Health, Shands Hospital
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Chicago
country: United States
facility: Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University -Riley Research
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Boston Children's Hospital - Harvard
state: Massachusetts
city: Grand Rapids
country: United States
facility: BSHS Office of Research
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: CHOP Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: UT Pediatric Neurosciences/Dell Children's Medical Center
state: Texas
city: Denton
country: United States
facility: Neurology Rare Disease Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Children's Hospital
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Institute of Research and Innovation
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Edegem
country: Belgium
facility: University Hospital Antwerp
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Brno
country: Czechia
facility: University Hospital Brno - Dept. of Pediatric Neurology
city: Prague
country: Czechia
facility: Motol University Hospital
city: Essen
country: Germany
facility: University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I
city: Freiburg
country: Germany
facility: University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders
city: Munich
country: Germany
facility: Dr. Von Haunersches Children'S Hospital - Lmu Munich
city: Bologna
country: Italy
facility: Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital
city: Gussago
country: Italy
facility: Nemo-Brescia Clinical Center For Neuromuscular Diseases
city: Pavia
country: Italy
facility: IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT
city: Roma
country: Italy
facility: Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Gdańsk
country: Poland
facility: University Clinical Centre in Gdansk - Dept. of Developmental Neurology
city: Poznań
country: Poland
facility: Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic
city: Warsaw
country: Poland
facility: The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology
city: Wrocław
country: Poland
facility: T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.
city: Donostia
country: Spain
facility: Donostia University Hospital
city: Esplugues De Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
city: Málaga
country: Spain
facility: Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit
city: Valencia
country: Spain
facility: La Fe University and Polytechnic Hospital
city: Glasgow
country: United Kingdom
facility: Royal Hospital For Children
state: Scotland
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
Study officials:
affiliation: Biohaven Pharmaceuticals, Inc.
name: Lindsey Lair, MD
role: STUDY_DIRECTOR
References: