start date: April 30, 2022
estimated completion: December 15, 2026
last updated: April 22, 2022
phase of development:
Phase 2/Phase 3
size / enrollment: 180
primary outcomes:
- Part 1 - Percentage of participants with adverse events (AEs)
- Up to 4.5 years
Part 1 - Incidence of relevant echocardiographic parameter z scores > 2
- Up to 4.5 years
Part 1 - Serum concentration of RO7204239
- Through Week 96
Part 1 - Time to maximum serum concentration (Cmax) of RO7204239
- Through Week 96
Part 1 - Area under the curve (AUC) of RO7204239
- Through Week 96
Part 1 - Trough concentration (Ctrough) of RO7204239
- Through Week 96
Part 1 - Plasma concentration of risdiplam
- Week 21
Part 1 - Plasma concentration of risdiplam metabolite (M1)
- Week 21
Part 1 - Cmax of risdiplam
- Week 21
Part 1 - AUC of risdiplam
- Week 21
Part 1 - Ctrough of risdiplam
- Week 21
Part 1 - Incidence of anti-drug antibodies (ADAs)
- Through Week 96
Part 1 - Change from baseline in serum concentration of total myostatin
- Through Week 85
Part 1 - Change from baseline in serum concentration of free latent myostatin
- Through Week 85
Part 1 - Change from baseline in serum concentration of mature myostatin
- Through Week 85
Part 1 - Percentage 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
- Week 24 of combination treatment
Part 1 - Percentage 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
- Week 24 of combination treatment
Part 2 - Change from baseline in Revised Hammersmith Scale (RHS) total score
- Week 72 of combination treatment (study Week 80)
secondary outcomes:
- Part 2 - Change from baseline in Motor Function Measure (MFM) Domain 1 + Domain 2 (D1 + D2) score
Week 72 of combination treatment (study Week 80)
- Part 2 - Change from baseline in MFM-32 total score
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
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
Week 72 of combination treatment (study Week 80)
- Part 2 - Change from baseline in lean muscle mass as assessed by full body dual energy X-ray absorptiometry (DXA) scan in participants aged at least 5 years
Week 72 of combination treatment (study Week 80)
- Part 2 - Percentage of participants with adverse events (AEs)
Up to 4.5 years
- Part 2 - Serum concentration of RO7204239
Through Week 80
- Part 2 - Cmax of RO7204239
Through Week 80
- Part 2 - AUC of RO7204239
Through Week 80
- Part 2 - Ctrough of RO7204239
Through Week 80
- Part 2 - Plasma concentration of risdiplam
Week 32
- Part 2 - Plasma concentration of risdiplam metabolite (M1)
Week 32
- Part 2 - Cmax of risdiplam
Week 32
- Part 2 - AUC of risdiplam
Week 32
- Part 2 - Ctrough of risdiplam
Week 32
- Part 2 - Incidence of ADAs
Through Week 80
inclusion criteria:
• Eligible Ages: 2 - 10
• Eligible Sexes: all
Inclusion Criteria:
Participants who are 2 to 10 years of age inclusive at screening
Participants who have a confirmed genetic diagnosis of 5q-autosomal recessive SMA
Symptomatic SMA disease, as per investigator's clinical judgement
Participants who are ambulant, where ambulant is defined as able to walk/run unassisted (i.e., without the use of assistive devices such as canes, walking sticks, crutches, walkers, person/hand-held assistance, braces, orthoses, over the malleoli insoles or any other type of support) 10 meters in
Participants who have received previous SMA disease-modifying therapies may be included provided that: Onasemnogene abeparvovec was received at least 90 days prior to screening. Participants should be tapered off steroids prior to receiving risdiplam. In addition, participants should have normal levels of liver function tests, coagulatory parameters, platelets, and troponin-I at 90 days after administration of onasemnogene abeparvovec or at least 1 month after tapering off corticosteroids, whichever comes later; Nusinersen last dose was received at least 90 days prior to screening; Risdiplam is switched to the investigational medicinal product (IMP) provided by the site
exclusion criteria: Criteria:
Concomitant or previous participation in any investigational drug or device study within 90 days prior to screening or 5 half-lives of the drug whichever is longer, with the exception of those who have completed a risdiplam study, or participated in a nusinersen or onasemnogene abeparvovec study
Receiving or have received previous administration of anti-myostatin therapies
For Part 1 participants aged 5 to 10 years only: contraindications for MRI scans including difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI
Any history of cell therapy
Hospitalization for a pulmonary event within the last 2 months or planned hospitalization at the time of screening
Past surgery for scoliosis or hip fixation in the 6 months preceding screening or planned within the next 9 months (Part 1) or 21 months (Part 2)
Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases considered to be clinically significant
Clinically significant ECG abnormalities at screening from average of triplicate measurement, abnormal findings at echocardiography, or cardiovascular disease indicating a safety risk for participants at the time of screening
Any major illness within 1 month before screening
Received any multidrug and toxin extrusion (MATE1/2K) substrates within 2 weeks before screening
Hereditary fructose intolerance
Used any of the following medications within 90 days prior to screening: riluzole, valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine, carnitine, growth hormone, anabolic steroids, probenecid, acetyl cholinesterase inhibitors, agents that could potentially increase or decrease muscle strength, and agents with known or presumed histone deacetylase (HDAC) inhibitory effect
Clinically significant abnormalities in laboratory test results at the time of screening
Ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to the constituents of its formulations
Clinically relevant history of anaphylactic reaction requiring inotropic support
Any abnormal skin conditions, pigmentation or lesions in the area intended for SC injection (abdomen) and that would prevent visualization of potential injection site reactions to RO7204239
Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening
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