A Study to Evaluate the Effectiveness and Safety of Risdiplam Administered in Pediatric Patients with Spinal Muscular Atrophy who Experienced a Plateau or Decline in Function After Gene Therapy

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] - Musculoskeletal Diseases [C05]

Trial duration

16 Dec 2024 → ongoing

Decision date (initial)

2024-02-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate, in pediatric patients, the effectiveness of risdiplam administered in patients who are experiencing a plateau or decline in function after onasemnogene abeparvovec

Secondary objectives 1

1. To evaluate, in pediatric patients, the safety and tolerability of risdiplam administered in patients who are experiencing a plateau or decline in function after onasemnogene abeparvovec

Conditions and MedDRA coding

Spinal Muscular Atrophy (SMA)

Regulatory references

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Confirmed diagnosis of 5q-autosomal recessive SMA, including genetic confirmation of homozygous deletion or compound heterozygosity predictive of loss of function of the survival of motor neuron 1 (SMN1) telomeric gene
2. Confirmed presence of two survival of motor neuron 2 (SMN2) centromeric gene copies as documented through laboratory testing
3. Administration of onasemnogene abeparvovec pre-symptomatically or post-symptomatically (<=3 months of symptoms)
4. Has received onasemnogene abeparvovec for SMA no less than 13 weeks (- 2 weeks) prior to enrollment
5. If treated with risdiplam prior to onasemnogene abeparvovec, risdiplam treatment must not have exceeded 3 weeks and must be discontinued 1 day prior to onasemnogene abeparvovec administration
6. In the opinion of the investigator, has demonstrated a plateau or decline in function post-gene therapy (with a duration of 6 months or less) documented by 2 individual time points in the functions as follows: - Swallowing AND - One (1) additional function/ability (respiratory, motor function, other) per appropriate expectation

Exclusion criteria 6

1. Previous or current enrollment in investigational study prior to initiation of study treatment
2. Any unresolved standard-of-care laboratory abnormalities per the onasemnogene abeparvovec prescribing information
3. Concomitant or previous administration of an SMN2-targeting antisense oligonucleotide
4. Patients requiring invasive ventilation or tracheostomy
5. Any major illness requiring hospitalization within 1 month before the screening examination or any febrile illness within 1 week prior to screening and up to first dose administration
6. Concomitant or previous use of an anti-myostatin agent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from Baseline in the Raw Score of Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) Gross Motor Score at 72 Weeks of Risdiplam Treatment in this population of SMA patients

Secondary endpoints 3

1. 1. Incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0)
2. 2. Incidence and severity of serious adverse events
3. 3. Incidence of treatment discontinuation due to adverse events

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

Head of CTRM Clinical Trial Regulatory Management, Product Development Regulatory

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Head of CTRM Clinical Trial Regulatory Management, Product Development Regulatory

Third parties 2

Locations

2 EU/EEA countries · 4 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 14 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