A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Teriflunomide in Adult Patients with Relapsing Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

9 Dec 2020 → ongoing

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2022-502609-14-00

EudraCT number

2019-004857-10

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of fenebrutinib compared with teriflunomide on the basis of annualized relapse rate (ARR)

Secondary objectives 3

1. 1. To evaluate the efficacy of fenebrutinib treatment compared with teriflunomide on the basis of time to onset of composite 24-week confirmed composite disability progression (cCDP24), Time to onset of composite 12-week confirmed disability progression (cCDP12), time to onset of 12-week confirmed disability progression (CDP12), time to onset of 24-week CDP (CDP24), total number of T1Gd+ lesions as detected by MRI, total number of new and/or enlarging T2-weighted lesions as detected by MRI, rate of percent change in total brain volume from Week 24 as assessed by MRI, change in patient-reported physical impacts of MS, time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modalities Test (SDMT) score, change from baseline to Week 48 in the concentration of blood neurofilament light chain (NfL) Time to onset of composite 12-week confirmed progression independent of relapse activity (cPIRA12)
2. 2. To evaluate the safety of fenebrutinib compared with teriflunomide
3. 3. To characterize the fenebrutinib pharmacokinetic profile

Conditions and MedDRA coding

Relapsing multiple sclerosis (RMS)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Expanded Disability Status Scale score (EDSS) of 0.0-5.5 at screening
2. 2. A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria
3. 3. Neurologically stable for at least 30 days prior to randomization and baseline assessments
4. 4. Ability to complete the 9-HPT for each hand in < 240 seconds
5. 5. Ability to perform the timed 25-Foot Walk Test in <150 seconds
6. 6. OLE Inclusion Criteria: Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib

Exclusion criteria 6

1. 1. A diagnosis of PPMS or non-active secondary progressive Multiple sclerosis (SPMS)
2. 2. Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.0
3. 3. Any known or suspected active infection at screening or baseline, or any major episode of infection requiring hospitalization or treatment with IV anti-microbials within 8 weeks prior to and during screening or treatment with oral anti-microbials within 2 weeks prior to and during screening. Onychomycosis is not exclusionary unless it is being treated with systemic therapy
4. 4. History of cancer including hematologic malignancy and solid tumors within 10 years of screening
5. 5. Known presence of other neurological disorders that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease
6. 6. Any concomitant disease that may require chronic treatment with systemic corticosteroids, or immunosuppressants during the course of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1.Annualized relapse rate

Secondary endpoints 17

1. 1. Time to onset of cCDP12
2. 2. Time to onset of CDP12
3. 3. Time to onset of cCDP24
4. 4. Time to onset of CDP24
5. 5. Total number of gadolinium-enhancing lesions on T1-weighted MRI lesions as detected by MRI
6. 6. Total number of new and/or enlarging T2-weighted lesions as detected by MRI
7. 7. Rate of percent change in total brain volume from Week 24 as assessed by MRI
8. 8. Rate of change from baseline in patient-reported physical impacts of MS, as measured by the Multiple Sclerosis Impact Scale (29-Item), Version 2 (MSIS-29 v2) physical scale
9. 9. Time to onset of 12-week confirmed 4-point worsening in SDMT score
10. 10. Change from baseline to Week 48 in the concentration of bloodneurofilament light chain (NfL)
11. 11. Composite 12-week confirmed progression independent of relapse activity (cPIRA12)
12. 12. The nature, frequency, timing, and severity of adverse events; serious adverse events; and adverse events leading to study treatment discontinuation or dose interruptions
13. 13. Change from baseline in targeted vital signs
14. 14. Change from baseline in targeted ECG parameters
15. 15. Change from baseline in clinical laboratory results
16. 16. Proportion of patients with suicidal ideation or behavior
17. 17. Plasma concentration of fenebrutinib at specified timepoints

Investigational products

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

Test 3

Placebo 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 19

Locations

7 EU/EEA countries · 53 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

Urgent safety measures 1 · Art. 54 CTR

Results and documents

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

Documents 143 files

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

Application history

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