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

Muscular Atrophy, Spinal Clinical Trial

— PUPFISH  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05808764
• Other study ID #: BN44619
• Secondary ID: 2023-505602-42-0
• Status: Recruiting
• Phase: Phase 2
• Start date: April 26, 2024
• Est. completion date: August 31, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BN44619 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 19 Days

Eligibility

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

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal

Intervention

Drug:
• Risdiplam
Participants will receive 0.15 mg/kg risdiplam orally once daily for 28 days.

Locations

Country	Name	City	State
Belgium	UZA	Edegem
Germany	Universitatsklinikum Essen	Essen
Italy	Fondazione Serena Onlus - CENTRO CLINICO NEMO	Milano	Emilia-Romagna
United States	University Of Michigan; Pediatric Nephrology	Ann Arbor	Michigan
United States	Ann and Robert H. Lurie Children Hospital of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Concentrations of Risdiplam		From Day 1 through Day 28
Primary	Area Under the Plasma Concentration-Time Curve (AUC) of Risdiplam		From Day 1 through Day 28
Primary	Steady-state Concentration (Css) of Risdiplam		From Day 1 through Day 28
Primary	Risdiplam Free Fraction		From Day 1 through Day 28
Primary	Percentage of Participants With Adverse Events		Up to 30 days after the final dose of study treatment (up to 58 days)
Primary	Percentage of Participants With Serious Adverse Events		Up to 30 days after the final dose of study treatment (up to 58 days)
Primary	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)