SMA Spinal Muscular Atrophy
Conditions
Interventions
Part 1: Participants naïve to risdiplam will be treated with risdiplam for at
least 8 weeks in the run-in period before randomization (2:1, RO7204239 plus
risdiplam: placebo plus risdiplam) into the
Sponsors
Roche Nederland B.V.
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Confirmed genetic diagnosis of 5q-autosomal recessive SMA • Part 2 only: available SMN2 gene copy number as previously determined by genetic testing and recorded in the participant's medical history • Symptomatic SMA disease, as per investigator*s clinical judgement • Age at screening: - Part 1 Cohorts A, B, and D: 5-10 years, inclusive - Part 1 Cohort C: 2-4 years, inclusive - Part 2: 2-25 years, inclusive • For Part 1 Cohorts A, B, and C and Part 2 only: 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
Exclusion criteria
Exclusion criteria: • For Part 1 cohorts A and B only: Participants with contraindications for magnetic resonance imaging (MRI) scan, difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI • Part 1 Cohort D only: - Participants who are unable to adopt the correct position to ensure 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 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 non-invasive ventilation (e.g., bilevel positive airway pressure) during the daytime. • For Part 2 only: Participants who recently initiated treatment (within 6 months prior to screening) with oral salbutamol or another B2-adrenergic agonist taken orally. Participants who have been on oral salbutamol (or another B2-adrenergic agonist) for 6 months or longer before screening and have shown good tolerance are allowed. The dose of B2-adrenergic agonist should remain stable as much as possible for the duration of the study. Use of inhaled B2-adrenergic agonists (e.g., for the treatment of asthma) is allowed. • 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. For those who have completed a risdiplam study, or participated in a nusinersen or onasemnogene abeparvovec study, the same criteria as described in Section 5.1 apply. • Received previous administration of anti-myostatin therapies • Any history of cell therapy • Participants who have been hospitalized for a pulmonary event within the last 2 months or planned hospitalization at the time of screening • Participants who have had 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) • Participants who have unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases considered to be clinically significant • Participants who have clinically significant electrocardiography (ECG) abnormalities at screening • Participants with clinically significant abnormal findings at echocardiography at screening • Participants who have had any major illness within 1 month before screening • Participants who have received any MATE1/2K substrates within 2 weeks before screening • Partici
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| part 1 (cohorts A-C): - Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of PK parameters for RO7204239 when administered in combination with risdiplam - Evaluation of PK parameters for risdiplam when administered in combination with RO7204239 - Evaluation of the immune response to RO7204239 in combination with risdiplam - Evaluation of the PD effects of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of RO7204239 PK/PD effects Part 2: - Evaluation of the efficacy of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam | — |
Secondary
| Measure | Time frame |
|---|---|
| Part 1 (cohorts A-C): Exploratory outcome: - Assessment of PD and efficacy of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of the efficacy of RO7204239 in combination with risdiplam by evaluation of the participant's mobility - Evaluation of the health-related quality of life of participants treated with RO7204239 in combination with risdiplam Part 1 (cohort D): - Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of PK parameters for RO7204239 when administered in combination with risdiplam - Evaluation of PK parameters for risdiplam when administered in combination with RO7204239 - Evaluation of the immune response to RO7204239 in combination with risdiplam - Evaluation of the PD effects of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of RO7204239 PK/PD effects - Assessment of the efficacy of RO7204239 in combination with risdiplam - Evaluation of the efficacy of RO7204239 in combination with risdiplam by evaluation of the participant's mobility - Evaluation of the health-related quality of life of participants treated with RO7204239 in combination with risdiplam Part 2: Secondary outcome: - Evaluation of the efficacy and PD of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of the safety of RO7204239 in combination with risdiplam compared with placebo in combination with risdiplam - Evaluation of PK parameters for RO7204239 when administered in combination with risdiplam - Evaluation of PK parameters for risdiplam when administered in combination with RO7204239 - Evaluation of the immune response to RO7204239 in combination with risdiplam Exploratory outcomes: - Evaluation of the efficacy of RO7204239 in combination with risdiplam compared with placebo in combination with | — |
Countries
Netherlands
Outcome results
None listed