A Study to Investigate the Pharmacokinetics and Safety of Risdiplam in Infants With Spinal Muscular Atrophy

Study Overview
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Brief Summary
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This study will evaluate the pharmacokinetics (PK) and safety of risdiplam in participants with spinal muscular atrophy (SMA) under 20 days of age at first dose.

Official Title
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A Phase II, Open-label Study to Investigate the Pharmacokinetics and Safety of Risdiplam in Infants With Spinal Muscular Atrophy

Conditions
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Muscular Atrophy, Spinal

Intervention / Treatment
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* Drug: Risdiplam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female newborn infant aged <20 days at first dose Newborn infants with genetic diagnosis of 5q-autosomal recessive SMA or newborn infants identified as positive for SMA via newborn screening or via prenatal testing. Gestational age equal to or greater than 37 weeks Receiving adequate nutrition and hydration at the time of screening Adequately recovered from any acute illness at baseline and considered well enough to participate in the study Parent/caregiver is willing to consider nasogastric, nasojejunal, or gastrostomy tube placement during the study to maintain safe hydration, nutrition, and treatment delivery, if recommended by the investigator. Exclusion Criteria: Presence of clinical symptoms or signs consistent with SMA Type 0 In the opinion of the investigator, inadequate venous or capillary blood access for the study procedures Systolic blood pressure or diastolic blood pressure or heart rate abnormalities Presence of clinically relevant electrocardiogram (ECG) abnormalities The infant (or the person breastfeeding the infant) taking any of the following: any inhibitor of CYP3A4 taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing, any inducer of CYP3A4 taken within 4 weeks (or within 5 times the elimination half-life, whichever is longer prior to dosing, and/or use of any multidrug and toxin extrusion (MATE) substrates taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing Concurrent or previous administration of nusinersen or onasemnogene abeparvovec Clinically significant abnormalities in laboratory test

Ages Eligible for Study
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Maximum Age: 19 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Risdiplam<br>Participants will receive risdiplam once daily for 28 days. | Drug: Risdiplam<br>* Participants will receive 0.15 mg/kg risdiplam orally once daily for 28 days.<br>* Other names: Evrysdi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentrations of Risdiplam |  | From Day 1 through Day 28 | 
| Area Under the Plasma Concentration-Time Curve (AUC) of Risdiplam |  | From Day 1 through Day 28 | 
| Steady-state Concentration (Css) of Risdiplam |  | From Day 1 through Day 28 | 
| Risdiplam Free Fraction |  | From Day 1 through Day 28 | 
| Percentage of Participants With Adverse Events |  | Up to 30 days after the final dose of study treatment (up to 58 days) | 
| Percentage of Participants With Serious Adverse Events |  | Up to 30 days after the final dose of study treatment (up to 58 days) | 
| Percentage of Participants With Treatment Discontinuation due to Adverse Events |  | Up to 30 days after the final dose of study treatment (up to 58 days) |