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

• Register: EUCTR
• Last refreshed on: 2 September 2024
• Main ID: EUCTR2019-003919-53-HU
• Date of registration: 23/04/2021
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: FENtrepid: A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared with Ocrelizumab in Adult Patients with Primary Progressive Multiple Sclerosis
• Scientific title: A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATE THE EFFICACY AND SAFETY OF FENEBRUTINIB COMPARED WITH OCRELIZUMAB IN ADULT PATIENTS WITH PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS
• Date of first enrolment: 17/06/2021
• Target sample size: 946
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-003919-53
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, New Zealand, Peru, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Switzerland, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
? Age 18-65 years inclusive at time of signing Informed Consent Form
? Ability to comply with the study protocol
? A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria
? Disability progression in the 12 months prior to screening, as assessed by the Pre-Baseline Disability Progression Questionnaire
? EDSS score from 3.0 to 6.5 inclusive at screening
? Pyramidal functional system sub score >=2 at screening
? 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
? For patients requiring symptomatic treatment for MS (e.g., fampridine, cannabis) and/or physiotherapy: treatment at a stable dose/regimen during the screening period prior to the initiation of study drug and plans to remain at a stable dose/regimen for the duration of study treatment Neurologically stable for at least 30 days prior to randomization and baseline assessments
? Ability to complete the 9 hole peg test for each hand in < 240 seconds
? Ability to perform timed 25-foot walk test in < 150 seconds
? For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 6 or 12 months (as applicable by the local label for ocrelizumab) after the final dose of study medication. Women must refrain from donating eggs during this same period.
? For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm as defined below:
o With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 28 days after the final dose of study medication to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 946
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
? 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
? History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
? Patients with a previous history of a serious IRR and/or any hypersensitivity reaction to ocrelizumab
? History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
? Immunocompromised state
? Known presence of other neurological disorders
? Evidence of clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal (GI) disease that, in the investigator’s opinion, would preclude patient participation
? Patients meeting the New York Heart Association Class III and Class IV criteria for congestive heart failure
? Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
? History of alcohol or other drug abuse within 12 months prior to screening
? Positive screening tests for active, latent, or inadequately treated hepatitis B and hepatitis C
? Evidence of active or latent or inadequately treated infection with tuberculosis (TB)
? History of hospitalizations or transfusion for a GI bleed
? Known bleeding diathesis
? Any condition possibly affecting oral drug absorption
? History of or currently active primary or secondary (non-drug related) immunodeficiency, including known history of HIV infection or IgG < 500 mg/dL
? Contraindications to mandatory premedications for infusion-related reactions (IRRs)
? Inability to complete an MRI scan or contraindication to gadolinium administration
? Lack of peripheral venous access
? Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
? Any previous history of transplantation or anti-rejection therapy
? Systemic corticosteroid therapy within 4 weeks prior to screening or during the screening period (inhaled and topical corticosteroids are allowed)
? Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
? Sensitivity or intolerance to any ingredient (including excipients) of fenebrutinib or ocrelizumab
? Receipt of a live or live attenuated vaccine within 6 weeks prior to randomization
? Need for systemic anticoagulation (oral or injectable) or anti platelet agent other than nonsteroidal anti-inflammatory drugs, aspirin, and other salicylates (aspirin up to 162 mg once daily is allowed)
? Previous treatment with fenebrutinib or another BTK inhibitor for any indication
? Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
? Treatment with strong CYP3A4 inhibitors, strong or moderate CYP3A4 inducers, within 7 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
? Treatment with CYP3A4 substrates with a narrow therapeutic window within 7 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
? Previous use of an anti-CD20 therapy, (including rituximab, ocrelizumab, ofatumumab, and ublituximab) within 6 months

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Primary Progressive multiple sclerosis
MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Product Name: fenebrutinib
Product Code: RO7010939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: FENEBRUTINIB
Other descriptive name: GDC-0853 RO7010939
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Ocrevus
Product Name: ocrelizumab
Product Code: RO4964913
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Ocrelizumab
Current Sponsor code: RO4964913
Other descriptive name: OCRELIZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Concentrate for solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

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

Timepoint(s) of evaluation of this end point: 1. Up to 4.7 years [estimated duration of Double-Blind Treatment (DBT)]

Secondary Objective: ? To evaluate the efficacy of fenebrutinib treatment compared with ocrelizumab
? To evaluate the safety of fenebrutinib compared with ocrelizumab
? To characterize the fenebrutinib PK profile

Primary end point(s): 1. Time to onset of composite 12-week confirmed disability progression (cCDP12)

Secondary Outcome(s)

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

Timepoint(s) of evaluation of this end point: 1-3. Up to 4.7 years (estimated duration of DBT)
4-5. At Week 120
6-11. Up to 4.7 years (estimated duration of DBT)
12. Week 0, 2, 12, 24, 48, 72, 96, 120, at treatment discontinuation or unscheduled visit

Secondary ID(s)

2019-003919-53-GB

GN41791

Source(s) of Monetary Support

F. Hoffman-La Roche Ltd.

Ethics review

Status: Approved
Approval date: 01/06/2021
Contact: