A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy

Exclusion 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
• •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
• •Participants with contraindications for MRI scan (including, but not restricted to, claustrophobia, pacemaker, artificial heart valves, cochlear implants, presence of foreign metal objects in heart or body, including spinal rods, intracranial vascular clips, insulin pumps, etc.), difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI
• •Participants who are unable to adopt the correct position to endure adequate quality of DXA scan acquisition, as determined by the DXA scan technologist
• •Participants who have contractures at screening that would interfere with DXA scan acquisition or functional assessments, as confirmed by the DXA scan technologist and clinical evaluator
• •For participants able to take steps only: Able to walk 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 ≤ 30 seconds as measured by the timed 10MWRT at screening
• •Participants who have severe scoliosis (curvature \> 40°) at screening based on the participant's most recent X-ray as performed per standard of care or scoliosis that would interfere with functional assessments, as confirmed by the clinical evaluator. An X-ray is not required if it is not clinically indicated (e.g., in participants with mild scoliosis)
• •Participants who require invasive ventilation, tracheostomy, or the use of noninvasive ventilation (e.g., bilevel positive airway pressure) during the daytime