Clinical trial NCT05808764: A Study to Investigate the Pharmacokinetics and Safety of Risdiplam in Infants With Spinal Muscular Atrophy
Official title: A Phase II, Open-label Study to Investigate the Pharmacokinetics and Safety of Risdiplam in Infants With Spinal Muscular Atrophy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Muscular Atrophy, Spinal
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-04-11
Enrollment: 10
Sex: ALL
Maximum age (years): 19
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Plasma Concentrations of Risdiplam
timeFrame: From Day 1 through Day 28
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Risdiplam
timeFrame: From Day 1 through Day 28
measure: Steady-state Concentration (Css) of Risdiplam
timeFrame: From Day 1 through Day 28
measure: Risdiplam Free Fraction
timeFrame: From Day 1 through Day 28
measure: Percentage of Participants With Adverse Events
timeFrame: Up to 30 days after the final dose of study treatment (up to 58 days)
measure: Percentage of Participants With Serious Adverse Events
timeFrame: Up to 30 days after the final dose of study treatment (up to 58 days)
measure: Percentage of Participants With Treatment Discontinuation due to Adverse Events
timeFrame: Up to 30 days after the final dose of study treatment (up to 58 days)
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children Hospital of Chicago
state: Illinois
city: Ann Arbor
country: United States
facility: University Of Michigan
state: Michigan
city: Gordonville
country: United States
facility: Clinic for Special Children.
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Hopital Universitaire des Enfants Reine Fabiola
city: Liege
country: Belgium
facility: CHR Citadelle
city: Ottawa
country: Canada
facility: Children'S Hospital of Eastern Ontario
state: Ontario
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Milano
country: Italy
facility: Fondazione Serena Onlus - CENTRO CLINICO NEMO
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Univeristario A. Gemelli
state: Emilia-Romagna
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Oslo
country: Norway
facility: OUS (Oslo University Hospital), Rikshospitalet
city: Gda?sk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Warszawa
country: Poland
facility: Instytut Pomnik - Centrum Zdrowia Dziecka
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: