Neuromuscular Diseases, SMA, Spinal Muscular Atrophy
Conditions
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.
Interventions
DB Phase: 35 mg/50 mg weekly subcutaneous injection
DRUGPlacebo
DB Phase: matching placebo 35 mg/50 mg weekly subcutaneous injection
Sponsors
Biohaven Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 21 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of taldefgrobep alfa compared to placebo in change in the 32 item Motor Function Measure (MFM-32) total score | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Upper Limb Module (RULM) score | Baseline to Week 48 | The RULM includes 20 items, graded from 0 to 2, with a maximum score of 37. Higher scores indicate better function. |
| Efficacy of taldefgrobep alfa compared to placebo in change in the Revised Hammersmith Scale (RHS) | Baseline to Week 48 | 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. |
| Change from Baseline in lean body mass | Baseline, Week 48 | Body mass will be measured as change in kg (greater change meaning more improvement) |
| Change from Baseline in bone mineral density | Baseline, Week 48 | Bone mineral density will be measured by Z-score change (higher score indicates improvement) |
| Change from baseline in Tanner staging | Baseline, Week 48 | — |
| Injection acceptability assessments | Week 48 | 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 |
| 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 | Up to 48 Weeks | — |
| Trough plasma concentration | Baseline, Week 12, Week 24, Week 36, Week 48 | — |
Countries
Belgium, Czechia, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORLindsey Lair, MD
Biohaven Pharmaceuticals, Inc.
Outcome results
None listed