Risdiplam works by helping the body produce more survival motor neuron (SMN) protein throughout the body. This means fewer motor neurons - nerve cells that pass impulses from nerves to muscles to cause movement - are lost, which may improve how well muscles work in people with SMA. RO7204239 is an investigational anti-myostatin antibody that is designed to target myostatin. Myostatin plays an important role in the regulation of skeletal muscle size by controlling growth. Inhibiting myostatin may help muscles grow in size and strength. RO7204239 in combination with risdiplam, which is designed to increase the amount of SMN protein throughout the body, has the potential to further improve motor function and clinical outcomes for people living with SMA. This trial will study the safety and efficacy of RO7204239 in combination with risdiplam in patients with spinal muscular atrophy (SMA). The trial has two parts; Part 1 is the dose-finding part in SMA patients that are either ambulant (aged 2-10 years) or non-ambulant (aged 5-10 years) within separate cohorts, and Part 2 is the pivotal part in SMA patients aged 2-25 years that are ambulant.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
97
RO7204239 will administered every 4 weeks (Q4W) by subcutaneous (SC) injection into the abdomen. RO7204239 will be investigated at low- and high-dose in Part 1.
Placebo will be administered Q4W by SC injection into the abdomen.
Risdiplam will be administered orally once daily (QD) for the duration of the study.
Boston Childrens Hospital
Boston, Massachusetts, United States
Columbia University Medical Center
New York, New York, United States
Sydney Children's Hospital
Randwick, New South Wales, Australia
UZ Gent
Ghent, Belgium
Chr de La Citadelle
Liège, Belgium
British Columbia Children's Hospital
Part 1 - Percentage of participants with adverse events (AEs)
Time frame: Up to 4.5 years
Part 1 - Incidence of relevant echocardiographic parameter z scores > 2
Time frame: Up to 4.5 years
Part 1 - Serum concentration of RO7204239
Time frame: Through Week 96
Part 1 - Time to maximum serum concentration (Cmax) of RO7204239
Time frame: Through Week 96
Part 1 - Area under the curve (AUC) of RO7204239
Time frame: Through Week 96
Part 1 - Trough concentration (Ctrough) of RO7204239
Time frame: Through Week 96
Part 1 - Plasma concentration of risdiplam
Time frame: Week 21
Part 1 - Plasma concentration of risdiplam metabolite (M1)
Time frame: Week 21
Part 1 - Cmax of risdiplam
Time frame: Week 21
Part 1 - AUC of risdiplam
Time frame: Week 21
Part 1 - Ctrough of risdiplam
Time frame: Week 21
Part 1 - Incidence of anti-drug antibodies (ADAs)
Time frame: Through Week 96
Part 1 - Change from baseline in serum concentration of total myostatin
Time frame: Through Week 85
Part 1 - Change from baseline in serum concentration of free latent myostatin
Time frame: Through Week 85
Part 1 - Change from baseline in serum concentration of mature myostatin
Time frame: Through Week 85
Part 1 - Percent change from baseline in the contractile area of skeletal muscle in the dominant thigh muscles as assessed by magnetic resonance imaging (MRI) in participants aged at least 5 years
Time frame: Week 24 of combination treatment
Part 1 - Percent change from baseline in the contractile area of skeletal muscle in the dominant calf muscles as assessed by MRI in participants aged at least 5 years
Time frame: Week 24 of combination treatment
Part 2 - Change from baseline in Revised Hammersmith Scale (RHS) total score
Time frame: Week 72 of combination treatment (study Week 80)
Part 2 - Change from baseline in Motor Function Measure (MFM) Domain 1 + Domain 2 (D1 + D2) score
Time frame: Week 72 of combination treatment (study Week 80)
Part 2 - Change from baseline in MFM-32 total score
Time frame: Week 72 of combination treatment (study Week 80)
Part 2 - Change from baseline in time taken to rise from the floor as measured by RHS Item 25
Time frame: Week 72 of combination treatment (study Week 80)
Part 2 - Change from baseline in time taken to walk/run 10 meters as measured by RHS Item 19
Time frame: Week 72 of combination treatment (study Week 80)
Part 2 - Percent change from baseline in lean mass as assessed by full body dual energy X-ray absorptiometry (DXA) scan in participants aged at least 5 years
Time frame: Week 72 of combination treatment (study Week 80)
Part 2 - Percentage of participants with adverse events (AEs)
Time frame: Up to 4.5 years
Part 2 - Serum concentration of RO7204239
Time frame: Through Week 80
Part 2 - Cmax of RO7204239
Time frame: Through Week 80
Part 2 - AUC of RO7204239
Time frame: Through Week 80
Part 2 - Ctrough of RO7204239
Time frame: Through Week 80
Part 2 - Plasma concentration of risdiplam
Time frame: Week 32
Part 2 - Plasma concentration of risdiplam metabolite (M1)
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Vancouver, British Columbia, Canada
The Hospital for Sick Children
Toronto, Ontario, Canada
McGill University Health Centre - Glen Site
Montreal, Quebec, Canada
Clinical Hospital Centre Zagreb
Zagreb, Croatia
Policlinico Agostino Gemelli
Rome, Lazio, Italy
...and 20 more locations
Time frame: Week 32
Part 2 - Cmax of risdiplam
Time frame: Week 32
Part 2 - AUC of risdiplam
Time frame: Week 32
Part 2 - Ctrough of risdiplam
Time frame: Week 32
Part 2 - Incidence of ADAs
Time frame: Through Week 80