A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Ocrelizumab in Adult Patients with Primary Progressive Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

24 Nov 2020 → ongoing

Decision date (initial)

2024-08-26

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann La Roche

External identifiers

EU CT number

2022-502611-10-00

EudraCT number

2019-003919-53

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To evaluate the efficacy of fenebrutinib compared with ocrelizumab in patients with PPMS regardless of adherence to randomized treatment

Secondary objectives 3

1. To evaluate the efficacy of fenebrutinib treatment compared with ocrelizumab
2. To evaluate the safety of fenebrutinib compared with ocrelizumab
3. To characterize the fenebrutinib PK profile

Conditions and MedDRA coding

Primary Progressive Multiple Sclerosis (PPMS)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

NA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Ability to comply with the study protocol
2. A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria
3. Disability progression in the 12 months prior to screening, as assessed by the Pre-Baseline Disability Progression Questionnaire
4. EDSS score from 3.0 to 6.5 inclusive at screening
5. Pyramidal functional subscore ≥ 2 at screening
6. For patients currently receiving proton pump inhibitors (PPIs) or H2 receptor antagonists (H2RAs): treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment

Exclusion criteria 6

1. For patients enrolled in Germany and in Italy only: Presence of T1Gd + lesion on the screening MRI
2. Any known or suspected active infection at screening or baseline, (excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks prior to and during screening or treatment with oral antimicrobials within 2 weeks prior to and during screening Onychomycosis is not exclusionary unless it is being treated with systemic therapy.
3. History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
4. Patients with a previous history of a serious IRR and/or any hypersensitivity reaction to ocrelizumab
5. History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
6. Immunocompromised state

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Time to onset of composite 12-week confirmed disability progression (cCDP12)

Secondary endpoints 13

1. 1. Time to onset of composite 24 week CDP (cCDP24)
2. 2. Time to onset of 12-week CDP (CDP12)
3. 3. Time to onset of 24 week CDP (CDP24)
4. 4. Percent change in total brain volume from Week 24 as assessed by MRI scan
5. 5. Percent change from screening to Week 120 in serum neurofilament light chain (NfL) levels
6. 6. Change patient-reported physical impacts of MS (as measured by Multiple Sclerosis Impact Scale, 29-Item [MSIS-29] physical scale)
7. 7. Time to onset of 12 week confirmed 4 point worsening in Symbol Digit Modality Test (SDMT) score
8. 8. The nature, frequency, timing, and severity of adverse events; serious adverse events; and adverse events leading to study treatment withdrawal
9. 9. Change from baseline in targeted vital signs
10. 10. Change from baseline in targeted ECG parameters
11. 11. Change from baseline in clinical laboratory results following study treatment administration
12. 12. Change from baseline in the proportion of patients with suicidal ideation or behavior, as assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
13. 13. 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 20

Locations

11 EU/EEA countries · 58 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 234 files

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

Application history

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