A study to investigate the safety, tolerability, and pharmacokinetics/pharmacodynamics of Risdiplam in adult and pediatric patients 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, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

12 May 2017 → 8 Feb 2025

Decision date (initial)

2024-01-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-506739-14-00

EudraCT number

2016-004184-39

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Safety, Others

1. To evaluate the safety and tolerability of risdiplam and to investigate the pharmacokinetics (PK) of risdiplam and metabolites as appropriate in SMA patients previously enrolled in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previously treated with nusinersen, AVXS-101, or olesoxime

Secondary objectives 1

1. 1. To investigate the PK - Pharmacodynamic (PD) relationship of risdiplam

Conditions and MedDRA coding

Spinal Muscular Atrophy (SMA)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002070-PIP01-16

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. 1. Males and females 6 months to 60 years of age inclusive (at screening)
2. 2. Confirmed diagnosis of 5q-autosomal recessive SMA
3. 3. Previous enrollment in Study BP29420 (Moonfish) with the splicing modifier RO6885247 or previous treatment with nusinersen (defined as having received ≥ 4 doses of nusinersen, provided that the last dose was received ≥ 90 days prior to screening),olesoxime (provided that the last dose was received ≤ 18 months and ≥ 90 days prior to screening) or onasemnogene abeparvovec (AVXS-101) (provided that the time of treatment was ≥ 12 months prior to screening)
4. 4. Adequately recovered from any acute illness at the time of screening and considered well enough to participate in the opinion of the Investigator
5. 5. For patients aged 2 years or younger at screening: • Receiving adequate nutrition and hydration (with or without gastrostomy) at the time of screening, in the opinion of the Investigator • Medical care meets local accepted standard of care, in the opinion of the Investigator • Would be able to complete all study procedures, measurements and visits, and the parent or caregiver of the patient has adequately supportive psychosocial circumstances, in the opinion of the Investigator • Parent or caregiver of patient is willing to consider nasogastric, nasojejunal or gastrostomy tube placement, as recommended by the Investigator, during the study to maintain safe hydration, nutrition and treatment delivery • Parent or caregiver of patient is willing to consider the use of noninvasive ventilation, as recommended by the Investigator during the study

Exclusion criteria 6

1. 1. With the exception of studies of olesoxime, AVXS-101, or nusinersen: Previous participation in any investigational drug or device study within 90 days prior to screening, or 5 half-lives of the drug, whichever is longer
2. 2. Any history of gene or cell therapy, with the exception of AVXS-101
3. 3. Unstable gastrointestinal, renal, hepatic, endocrine, or cardiovascular system diseases as considered to be clinically significant by the Investigator
4. 4. Inadequate venous or capillary blood access for the study procedures, in the opinion of the Investigator
5. 5. For patients aged <2 years, hospitalization for a pulmonary event within 2months prior to screening and pulmonary function not fully recovered at the time of screening
6. 6. Lactating women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 11

1. 1. Incidence and severity of adverse events and serious adverse events with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events scale, Version 4.0
2. 2. Incidence of treatment discontinuations due to adverse events
3. 3. Incidence of abnormal vital signs, laboratory, and ECG abnormalities
4. 4. Incidence of clinically significant findings on ophthalmological examination
5. 5. Incidence of clinically significant findings on neurological examination
6. 6. Incidence of clinically significant findings in Physical examination
7. 7. Incidence of emergence or worsening of symptoms as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS) (adult version for adults and adolescents, pediatric version for patients aged 6-11 years)
8. 8. Mean plasma concentrations of Risdiplam and metabolites
9. 9. Peak plasma concentration (Cmax)
10. 10. Area under the curve (AUC)
11. 11. Concentration at the end of a dosing interval (Ctrough)

Secondary endpoints 2

1. 1. SMN mRNA levels in blood
2. 2. SMN protein levels in blood

Investigational products

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

Test 1

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 10

Locations

5 EU/EEA countries · 14 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 78 files

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

Application history

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