A Study to Investigate the Safety and Efficacy of RO7204239 in Combination With Risdiplam (RO7034067) in Participants With Spinal Muscular Atrophy
- Conditions
- Spinal Muscular Atrophy (SMA)
- Registration Number
- NCT05115110
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> - Age at screening: Part 1 Cohorts A (ambulant participants), B (ambulant<br> participants), and D (non-ambulant participants): 5-10 years, inclusive; Part 1<br> Cohort C (ambulant participants): 2-4 years, inclusive; Part 2 (ambulant<br> participants): 2-25 years, inclusive<br><br> - Participants who have a confirmed genetic diagnosis of 5q-autosomal recessive SMA<br><br> - Symptomatic SMA disease, as per investigator's clinical judgement<br><br> - Participants who have received previous SMA disease-modifying therapies may be<br> included provided that: Onasemnogene abeparvovec was received at least 90 days prior<br> to screening. Participants should be tapered off steroids prior to receiving<br> risdiplam. In addition, participants should have normal levels of liver function<br> tests, coagulatory parameters, platelets, and troponin-I at 90 days after<br> administration of onasemnogene abeparvovec or at least 1 month after tapering off<br> corticosteroids, whichever comes later; Nusinersen last dose was received at least<br> 90 days prior to screening; Risdiplam is switched to the investigational medicinal<br> product (IMP) provided by the site<br><br>Inclusion Criteria for Part 1 Cohorts A, B, and C and Part 2 only:<br><br> - Participants who are ambulant, where ambulant is defined as able to walk/run<br> unassisted (i.e., without the use of assistive devices such as canes, walking<br> sticks, crutches, walkers, person/hand-held assistance, braces, orthoses, over the<br> malleoli insoles or any other type of support) 10 meters in = 30 seconds as measures<br> by the Timed 10-Meter Walk/Run Test [10MWRT] at screening<br><br>Inclusion Criteria for Part 1 Cohort D only:<br><br> - Participants who are able to sit, defined by: A score of 3 on Item 9 of the MFM32<br> (sitting without upper limb support while maintaining contact between the two hands<br> for 5 seconds); A score of at least 2 on Item 10 of the MFM32 (while seated, leaning<br> forward to touch a tennis ball and sitting back again, either with or without upper<br> limb support)<br><br> - Participants who are able to raise a standardized plastic cup with a 200g weight in<br> it to the mouth, using both hands if necessary, defined by a score of 3 on the entry<br> item of the Revised Upper Limb Module (RULM)<br><br>Exclusion Criteria:<br><br> - Concomitant or previous participation in any investigational drug or device study<br> within 90 days prior to screening or 5 half-lives of the drug whichever is longer,<br> with the exception of those who have completed a risdiplam study, or participated in<br> a nusinersen or onasemnogene abeparvovec study<br><br> - Receiving or have received previous administration of anti-myostatin therapies<br><br> - Any history of cell therapy<br><br> - Hospitalization for a pulmonary event within the last 2 months or planned<br> hospitalization at the time of screening<br><br> - Past surgery for scoliosis or hip fixation in the 6 months preceding screening or<br> planned within the next 9 months (Part 1) or 21 months (Part 2)<br><br> - Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system<br> diseases considered to be clinically significant<br><br> - Clinically significant ECG abnormalities at screening from average of triplicate<br> measurement, abnormal findings at echocardiography, or cardiovascular disease<br> indicating a safety risk for participants at the time of screening<br><br> - Any major illness within 1 month before screening<br><br> - Received any multidrug and toxin extrusion (MATE1/2K) substrates within 2 weeks<br> before screening<br><br> - Hereditary fructose intolerance<br><br> - Used any of the following medications within 90 days prior to screening: riluzole,<br> valproic acid, hydroxyurea, sodium phenylbutyrate, butyrate derivatives, creatine,<br> carnitine, growth hormone, anabolic steroids, probenecid, acetyl cholinesterase<br> inhibitors, agents that could potentially increase or decrease muscle strength, and<br> agents with known or presumed histone deacetylase (HDAC) inhibitory effect<br><br> - Clinically significant abnormalities in laboratory test results at the time of<br> screening<br><br> - Ascertained or presumptive hypersensitivity to RO7204239 or risdiplam, or to the<br> constituents of its formulations<br><br> - Clinically relevant history of anaphylactic reaction requiring inotropic support<br><br> - Any abnormal skin conditions, pigmentation or lesions in the area intended for SC<br> injection (abdomen) and that would prevent visualization of potential injection site<br> reactions to RO7204239<br><br> - Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs<br> within 90 days prior to screening<br><br>Exclusion Criteria for Part 1 Cohorts A and B only:<br><br> - Participants with contraindications for MRI scan (including, but not restricted to,<br> claustrophobia, pacemaker, artificial heart valves, cochlear implants, presence of<br> foreign metal objects in heart or body, including spinal rods, intracranial vascular<br> clips, insulin pumps, etc.), difficulties maintaining a prolonged supine position,<br> or any other clinical history or examination finding that would pose a potential<br> hazard in combination with MRI<br><br>Exclusion Criteria for Part 1 Cohort D only:<br><br> - Participants who are unable to adopt the correct position to endure adequate quality<br> of DXA scan acquisition, as determined by the DXA scan technologist<br><br> - Participants who have contractures at screening that would interfere with DXA scan<br> acquisition or functional assessments, as confirmed by the DXA scan technologist and<br> clinical evaluator<br><br> - For participants able to take steps only: Able to walk unassisted (i.e., without the<br> use of assistive devices such as canes, walking sticks, crutches, walkers,<br> person/hand held assistance, braces, orthoses, over the malleoli insoles or any<br> other type of support) 10 meters in = 30 seconds as measured by the timed 10MWRT at<br> screening<br><br> - Participants who have severe scoliosis (curvature > 40°) at screening based on the<br> participant's most recent X-ray as performed per standard of care or scoliosis that<br> would interfere with functional assessments, as confirmed by the clinical evaluator.<br> An X-ray is not required if it is not clinically indicated (e.g., in participants<br> with mild scoliosis)<br><br> - Participants who require invasive ventilation, tracheostomy, or the use of<br> noninvasive ventilation (e.g., bilevel positive airway pressure) during the daytime
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method