Spinal Muscular AtrophyPhase 3RESILIENTNCT05337553
A Study to Evaluate the Efficacy and Safety of Taldefgrobep Alfa in Participants With Spinal Muscular Atrophy
A Phase 3 study testing taldefgrobep alfa in people with Spinal Muscular Atrophy and Neuromuscular Diseases, run by Biohaven Pharmaceuticals, Inc. at 53 sites in 9 countries.
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 and/or risdiplam and/or have a history of onasemnogene abeparvovec, compared to placebo. Read more about this study
- Who is it for?
- Ages 4 to 21 years
- Conditions the study is for
- Spinal Muscular Atrophy, Neuromuscular Diseases, SMA
- What is being tested?
- taldefgrobep alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 269 participants
- Where
- 53 sitesin 9 countries
- Study dates
- 6 Jul 2022to Dec 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
53 sites in 9 countries.
53 sites in 9 countries
United States30 sites
Rare Disease Research
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
UT Pediatric Neurosciences/Dell Children's Medical Center
Austin, Texas, 78723
Boston Children's Hospital - Harvard
Boston, Massachusetts, 02115
University of Virginia Children's Hospital
Charlottesville, Virginia, 22903
Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Neurology Rare Disease Center
Denton, Texas, 75208
Duke University Medicine
Durham, North Carolina, 27705
University of Kansas Medical Center
Fairway, Kansas, 66205
Cook Children's Hospital
Fort Worth, Texas, 76104
UF Health, Shands Hospital
Gainesville, Florida, 32610
BSHS Office of Research
Grand Rapids, Michigan, 49503
Penn State College of Medicine
Hershey, Pennsylvania, 17033
Indiana University -Riley Research
Indianapolis, Indiana, 46202
University of Iowa
Iowa City, Iowa, 52242
UCSD & Rady Children's
La Jolla, California, 92037
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Columbia University Medical Center
New York, New York, 10032
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
CHOP Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Phoenix Children's
Phoenix, Arizona, 85016
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
UCSF Benioff Children's Hospital, Medical Center
San Francisco, California, 94158
Washington University in St. Louis
St Louis, Missouri, 63110
Stony Brook University Hospital
Stony Brook, New York, 11794
MultiCare Institute of Research and Innovation
Tacoma, Washington, 98405
Italy4 sites
Irccs Institute of Neurological Sciences of Bologna - Bellaria Hospital
Bologna, 40139
Nemo-Brescia Clinical Center For Neuromuscular Diseases
Gussago, 25064
IRCCS NEUROLOGICAL INSTITUTE C. MONDINO CHILD and NEUROPSYCHIATRIC UNIT
Pavia, 27100
Bambino Gesù Children'S Research Hospital Irccs - San Paolo Office Dept. of Neuroscience
Roma, 00165
Poland4 sites
University Clinical Centre in Gdansk - Dept. of Developmental Neurology
Gdansk, 80-925
Heliodor Swiecicki Clinical Hospital At Medical University - Child and Adolescents Neurology Clinic
Poznan, 60-355
The Children'S Memorial Health Institute - Dept. of Neurology and Epileptology
Warsaw, 04-730
T. Marciniak Lower Silesian Specialist Hospital, Pediatric Neurology Dept.
Wroclaw, 54-049
Spain4 sites
Donostia University Hospital
Donostia / San Sebastian, 20014
Hospital Sant Joan de Déu
Esplugues de Llobregat, 08950
Maternal-Child'S Hospital of Málaga, Regional University Hospital - Pediatric Neurology Unit
Málaga, 29011
La Fe University and Polytechnic Hospital
Valencia, 46026
Belgium3 sites
University Hospital Antwerp
Edegem, 02650
University Hospital Ghent
Ghent, 09000
University Hospital Leuven
Leuven, 03000
Germany3 sites
University Hospital Essen (Public-Law Institution) - Dept. of Pediatrics I
Essen, 45147
University Hospital Freiburg, Center For Children and Adolescent Medicine, Dept. of Neuropediatrics and Muscle Disorders
Freiburg im Breisgau, 79106
Dr. Von Haunersches Children'S Hospital - Lmu Munich
Munich, 80337
Czechia2 sites
University Hospital Brno - Dept. of Pediatric Neurology
Brno, 625 00
Motol University Hospital
Prague, 150 06
United Kingdom2 sites
Royal Hospital For Children
Glasgow, Scotland, G51 4TF
John Radcliffe Hospital
Oxford, OX3 9DU
About this study
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
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.
Read the 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.
- Conditions
- Spinal Muscular Atrophy, Neuromuscular Diseases, SMA
- Being tested
- taldefgrobep alfa, Placebo
- Medical subject headings
- Muscular Atrophy, Spinal, Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
taldefgrobep alfaDrug
Also called BHV-2000, BMS-986089
DB Phase: 35 mg/50 mg weekly subcutaneous injection
PlaceboDrug
DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
taldefgrobep alfaDrug
Also called BHV-2000, BMS-986089
Extension Phase: 35 mg/50 mg weekly subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| taldefgrobep alfa | Experimental | 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 Open label Extension (OLE) phase. Receives: Drug: taldefgrobep alfa |
| Placebo | Placebo comparator | 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 OLE phase. Receives: Drug: Placebo; Drug: taldefgrobep alfa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 scores from the 32 items are summed and transformed to a 0-100 scale, with higher scores reflecting higher levels of functional abilities.
Measured: Baseline to Week 48
Secondary outcomes (8)
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score
The RULM includes 20 items, graded from 0 to 2, with a maximum score of 37. Higher scores indicate better function.
Measured: Baseline to Week 48
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS)
The RHS has a maximum score of 69 points (33 items are scored 0-2, and 3 items scored 0-1). Higher scores indicate better function.
Measured: Baseline to Week 48
Change from Baseline in lean body mass
Body mass will be measured as change in kg (greater change meaning more improvement)
Measured: Baseline, Week 48
Change from Baseline in bone mineral density
Bone mineral density will be measured by Z-score change (higher score indicates improvement)
Measured: Baseline, Week 48
Change from baseline in Tanner staging
Measured: Baseline, Week 48
Injection acceptability assessments
If local injection site reactions (such as redness, itching, swelling, hardening or bruising) are experienced, the acceptability is scored on a scale of 1-5 with 1 being totally acceptable and 5 being not at all acceptable If pain is experienced at the injection site, pain will be scored on a scale of 1-5 with 1 being totally acceptable and 5 being not at all acceptable
Measured: Week 48
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
Measured: Up to 48 Weeks
Trough plasma concentration
Measured: Baseline, Week 12, Week 24, Week 36, Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start6 Jul 2022
- Primary completion25 Sep 2024
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 269 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biohaven Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lindsey Lair, MD, Study director, Biohaven Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05337553
- Sponsor's protocol ID
- BHV2000-301
- Acronym
- RESILIENT
- Status last verified
- May 2026
- First submitted
- 14 Apr 2022
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05337553
- Acronym / sponsor ID
- RESILIENT / BHV2000-301
- Conditions
- Spinal Muscular Atrophy, Neuromuscular Diseases, SMA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 269 participants (actual)
- Lead sponsor
- Biohaven Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Jul 2022 (actual)
- Primary completion
- 25 Sep 2024 (actual)
- Study completion
- Dec 2027 (estimated)
- First posted
- 20 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| taldefgrobep alfa | Experimental | Drug: taldefgrobep alfataldefgrobep 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 Open label Extension (OLE) phase. |
| Placebo | Placebo comparator | Drug: Placebo, Drug: taldefgrobep alfaPlacebo - 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 OLE phase. |
Who may qualify
- Ages
- 4 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- 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 (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| taldefgrobep alfaAlso: BHV-2000, BMS-986089DB Phase: 35 mg/50 mg weekly subcutaneous injection | Drug | taldefgrobep alfa |
| PlaceboDB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection | Drug | Placebo |
| taldefgrobep alfaAlso: BHV-2000, BMS-986089Extension Phase: 35 mg/50 mg weekly subcutaneous injection | Drug | Placebo, taldefgrobep alfa |
Primary outcome
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 scores from the 32 items are summed and transformed to a 0-100 scale, with higher scores reflecting higher levels of functional abilities.
8 secondary outcomes
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score
Time frame: Baseline to Week 48
Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS)
Time frame: Baseline to Week 48
Change from Baseline in lean body mass
Time frame: Baseline, Week 48
Change from Baseline in bone mineral density
Time frame: Baseline, Week 48
Change from baseline in Tanner staging
Time frame: Baseline, Week 48
Injection acceptability assessments
Time frame: Week 48
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
Time frame: Up to 48 Weeks
Trough plasma concentration
Time frame: Baseline, Week 12, Week 24, Week 36, Week 48
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lindsey Lair, MD study director
Biohaven Pharmaceuticals, Inc.
53 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing taldefgrobep alfa in people with Spinal Muscular Atrophy and Neuromuscular Diseases, run by Biohaven Pharmaceuticals, Inc. at 53 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Italy, Poland, Spain, Belgium and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.