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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Muscular Atrophy, Spinal
• Intervention / Treatment: Drug: Risdiplam

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BN44619 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risdiplam; Participants will receive risdiplam once daily for 28 days.	Drug: Risdiplam; Participants will receive 0.15 mg/kg risdiplam orally once daily for 28 days.; Other Names: Evrysdi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2024
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 11, 2023

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Risdiplam
• Other Study ID Numbers: BN44619; 2023-505602-42-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No