Outcome measures in SMA patients treated with Risdiplam.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

13 Jun 2023 → 2 Oct 2024

Decision date (initial)

2022-11-28

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Roche

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Others

The primary objective of the study is: To study a wide range of clinical, functional, and patient-reported outcome measures in adult patients with SMA type 2 or 3 or patients with up to 4 SMN2-gene copies treated with Risdiplam (Evrysdi®) for a duration of 24 months.

Secondary objectives 1

1. The secondary objectives of the study are: To identify if biomarkers in blood correlate to clinical and functional outcome measures in adult SMA patients treated with Risdiplam; AND To assess the safety and tolerability of Risdiplam treatment.

Conditions and MedDRA coding

Spinal Muscular Atrophy (SMA)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Participants eligible for inclusion in this Trial must meet all of the following criteria: 1) Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures; 2) Use of highly effective methods of birth control; Highly effective contraceptives are methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); • progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); • intrauterine device (IUD); • intrauterine hormone-releasing system ( IUS); • bilateral tubal occlusion; • vasectomised partner; • sexual abstinence. A male participant who is sexually active with a woman of childbearing potential and who has not had a vasectomy must agree to use a barrier method of birth control (eg, either a condom [with spermicidal foam/gel/film/cream/suppository or a partner with an occlusive cap [diaphragm or cervical/vault caps] plus spermicidal foam/gel/film/cream/suppository), during the study and for at least 4 months after receiving the last administration of Risdiplam. The time period during which highly effective contraception is required after the last dose of Risdiplam is 1 month for female patients of childbearing potential and 4 months for male patients. Male participants will be informed that they may consider sperm preservation prior to treatment initiation; 3) Male or female patients of an adult age (i.e., 18 years or older); 4) Confirmed genetic diagnosis of 5q-autosomal recessive Spinal Muscular Atrophy (SMA) (i.e., deletions of both SMN1-genes or mutations in both SMN1- genes have been genetically proven); 5) Patients eligible for treatment with Risdiplam (Evrysdi®) (i.e., SMA type 2 or 3 or patients with up to 4 SMN2-gene copies and no permanent invasive ventilation, corresponding to the RIZIV reimbursement criteria for Evrysdi® (Risdiplam) in Belgium) ), that are either treatment-naive or are already being treated with Evrysdi® (Risdiplam) in Standard-Of-Care.

Exclusion criteria 1

1. Participants eligible for this Trial must not meet any of the following criteria: 1) Any disorder, which in the Investigator’s opinion might jeopardise the participant’s safety or compliance with the protocol; 2) Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate, highly effective contraceptive. A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. Exclusion criterion is a male participant who is sexually active with a woman of childbearing potential and who has not had a vasectomy and does not agree to use a barrier method of birth control (e.g. a condom) during the study until at least 4 months after the last dose of Risdiplam; 3) Participation in an interventional Trial with an investigational medicinal product (IMP) or device; 4) Patients younger than 18 years of age at the time of the study; 5) Patients without genetically confirmed diagnosis of 5q-SMA at the time of the study; 6) SMA patients not eligible for treatment with Risdiplam according to the RIZIV reimbursement criteria for Risdiplam (Evrysdi®) in Belgium; 7) Patients treated with Risdiplam (Evrysdi®) in a Compassionate Use Programme (CUP) at the time of inclusion; 8) Patients treated with nusinersen (Spinraza®) before or at the time of inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of this study is: The change in clinical and functional outcome measures in adult patients with SMA type 2 or 3 or patients with up to 4 SMN2-gene copies treated with Risdiplam from baseline to 24 months.

Secondary endpoints 1

1. The secondary endpoints of this study are: Quantitative changes of biomarkers in blood (neurofilament light chain and neurofilament heavy chain) in adult patients with SMA type 2 or 3 or patients with up to 4 SMN2-gene copies treated with Risdiplam from baseline to 24 months, AND To assess the safety and tolerability of Risdiplam treatment.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Kristl Claeys

Public contact point

Organisation

UZ Leuven

Contact name

Kristl Claeys

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

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 2 files

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

Application history

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