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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

30 Apr 2024 → ongoing

Decision date (initial)

2024-03-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann La Roche

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety

To characterize the risdiplam PK profile and to evaluate the safety of risdiplam

Conditions and MedDRA coding

Spinal Muscular Atrophy (SMA)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Male or female newborn infant aged <20 days at first dose.
2. 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.
3. Gestational age equal to or greater than 37 weeks.
4. Receiving adequate nutrition and hydration at the time of screening.
5. Adequately recovered from any acute illness at baseline and considered well enough to participate in the study.
6. 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 6

1. Presence of clinical symptoms or signs consistent with SMA Type 0.
2. In the opinion of the investigator, inadequate venous or capillary blood access for the study procedures.
3. Systolic blood pressure or diastolic blood pressure or heart rate abnormalities or presence of clinically relevant electrocardiogram (ECG) abnormalities.
4. 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.
5. Concurrent or previous administration of nusinersen or onasemnogene abeparvovec.
6. Clinically significant abnormalities in laboratory test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 12

1. Plasma concentration of risdiplam and metabolite(s) as applicable at specified timepoints
2. AUC
3. Concentration at the end of a dosing interval to assess steady-state
4. Other PK parameters as appropriate
5. Risdiplam free fraction
6. Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0
7. Incidence and severity of serious adverse events
8. Incidence of treatment discontinuation due to adverse events
9. Incidence of abnormal laboratory values
10. Incidence of abnormal ECG values
11. Vital signs abnormalities, including body temperature, systolic and diastolic blood pressure, heart rate, respiratory rate
12. Physical examination, including detailed examination of the skin and mouth

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 4

Locations

6 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 37 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications