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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
269
DB Phase: 35 mg/50 mg weekly subcutaneous injection
DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
Extension Phase: 35 mg/50 mg weekly subcutaneous injection
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.
Time frame: Baseline to Week 48
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.
Time frame: 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.
Time frame: 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)
Time frame: Baseline, Week 48
Change from Baseline in bone mineral density
Bone mineral density will be measured by Z-score change (higher score indicates improvement)
Time frame: Baseline, Week 48
Change from baseline in Tanner staging
Time frame: 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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Phoenix Children's
Phoenix, Arizona, United States
UCSD & Rady Children's
La Jolla, California, United States
Children's Hospital of Los Angeles
Los Angeles, California, United States
UCSF Benioff Children's Hospital, Medical Center
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
UF Health, Shands Hospital
Gainesville, Florida, United States
Rare Disease Research
Atlanta, Georgia, United States
Northwestern University - Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Indiana University -Riley Research
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
...and 43 more locations
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