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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04544449




Registration number
NCT04544449
Ethics application status
Date submitted
4/09/2020
Date registered
10/09/2020
Date last updated
13/04/2021

Titles & IDs
Public title
A Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Ocrelizumab In Adult Participants 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.
Secondary ID [1] 0 0
2019-003919-53
Secondary ID [2] 0 0
GN41791
Universal Trial Number (UTN)
Trial acronym
FENtrepid
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis, Primary Progressive 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - fenebrutinib
Treatment: Drugs - ocrelizumab
Treatment: Drugs - placebo

Experimental: fenebrutinib - Participants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.

Active Comparator: ocrelizumab - Participants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.


Treatment: Drugs: fenebrutinib
Participants will receive fenebrutinib.

Treatment: Drugs: ocrelizumab
Participants will receive ocrelizumab.

Treatment: Drugs: placebo
Participants will receive fenebrutinib-matching placebo and ocrelizumab-matching placebo.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to onset of composite 12-week confirmed disability progression (cCDP12)
Timepoint [1] 0 0
Minimum of 120 weeks
Secondary outcome [1] 0 0
Time to onset of composite 24-week CDP (cCDP24)
Timepoint [1] 0 0
Minimum of 120 weeks
Secondary outcome [2] 0 0
Time to onset of 12-week CDP (CDP12)
Timepoint [2] 0 0
Minimum of 120 weeks
Secondary outcome [3] 0 0
Time to onset of 24-week CDP (CDP24)
Timepoint [3] 0 0
Minimum of 120 weeks
Secondary outcome [4] 0 0
Percentage Change in Total Brain Volume assessed by MRI
Timepoint [4] 0 0
From Week 24 to Week 120
Secondary outcome [5] 0 0
Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) - Measured by the Multiple Sclerosis Impact Scale, 29-Item [MSIS-29] physical scale.
Timepoint [5] 0 0
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
Secondary outcome [6] 0 0
Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) score
Timepoint [6] 0 0
Minimum of 120 weeks
Secondary outcome [7] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [7] 0 0
Up to 4.5 years
Secondary outcome [8] 0 0
Plasma Concentrations of fenebrutinib at specified timepoints
Timepoint [8] 0 0
Up to 4.5 years

Eligibility
Key inclusion criteria
- A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et
al. 2018).

- Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.

- For participants currently receiving proton pump inhibitors (PPIs), H2-receptor
antagonists (H2RAs), symptomatic treatment for Multiple Sclerosis (MS) (e.g.
fampridine, cannabis) and/or physiotherapy: 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.

- Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in < 240 seconds.

- Ability to perform Timed 25-Foot Walk Test (T25FWT).

- For female participants of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive measures, and refrain
from donating eggs.

- For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and refrain from donating sperm.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any known or suspected active infection at screening, including but not limited to a
positive screening tests for Hepatitis B and C, an active or latent or inadequately
treated infection with tuberculosis (TB), a confirmed or suspected progressive
multifocal leukoencephalopathy (PML).

- Participants with a previous history of a serious Infusion-Related Reaction (IRR)
(Common Terminology Criteria for Adverse Events [CTCAE] Grade >= 4) and/or any
hypersensitivity reaction to ocrelizumab.

- History of cancer including hematologic malignancy and solid tumors within 10 years of
screening.

- Known presence of other neurological disorders, clinically significant cardiovascular,
psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal
disease.

- Any concomitant disease that may require chronic treatment with systemic
corticosteroids, immunosuppressants or specific medication that could impact the
primary evaluation of the study.

- History of alcohol or other drug abuse within 12 months prior to screening.

- Female participants who are pregnant or breastfeeding or intending to become pregnant
during the study or 6 or 12 months (as applicable from the local label for
ocrelizumab) after final dose of study drug.

- Male participants intending to father a child during the study or 6 or 12 months (as
applicable from the local label for ocrelizumab) after final dose of study drug.

- Lack of peripheral venous access.

- Any previous treatment with immunomodulatory or immunosuppressive medication without
an appropriate washout period.

- Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.

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.

- For female participants of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive measures, and refrain
from donating eggs.

- For male participants: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and refrain from donating sperm.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Box Hill Hospital; Department of Neurology - Box Hill
Recruitment hospital [5] 0 0
Austin Hospital; Department of Neurology - Heidelberg
Recruitment hospital [6] 0 0
Royal Melbourne Hospital; Department of Neurology - Parkville
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
2305 - New Lambton
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Indiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
United States of America
State/province [14] 0 0
West Virginia
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Argentina
State/province [16] 0 0
Caba
Country [17] 0 0
Argentina
State/province [17] 0 0
Ciudad Autonoma de Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
Ciudad Autónoma de Buenos Aires
Country [19] 0 0
Argentina
State/province [19] 0 0
Cordoba
Country [20] 0 0
Argentina
State/province [20] 0 0
Rosario
Country [21] 0 0
Argentina
State/province [21] 0 0
San Miguel
Country [22] 0 0
Canada
State/province [22] 0 0
New Brunswick
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Quebec
Country [25] 0 0
France
State/province [25] 0 0
Bordeaux
Country [26] 0 0
France
State/province [26] 0 0
Bron
Country [27] 0 0
France
State/province [27] 0 0
Nantes
Country [28] 0 0
France
State/province [28] 0 0
Nice
Country [29] 0 0
France
State/province [29] 0 0
Strasbourg
Country [30] 0 0
Israel
State/province [30] 0 0
Haifa
Country [31] 0 0
Israel
State/province [31] 0 0
Tel Aviv
Country [32] 0 0
Peru
State/province [32] 0 0
Bellavista
Country [33] 0 0
Peru
State/province [33] 0 0
Lima
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Krasnojarsk
Country [35] 0 0
Russian Federation
State/province [35] 0 0
Leningrad
Country [36] 0 0
Russian Federation
State/province [36] 0 0
Moskovskaja Oblast
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Tatarstan
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Ekaterinburg
Country [39] 0 0
Russian Federation
State/province [39] 0 0
Krasnoyarsk
Country [40] 0 0
Russian Federation
State/province [40] 0 0
St. Petersburg
Country [41] 0 0
Turkey
State/province [41] 0 0
Ankara
Country [42] 0 0
Turkey
State/province [42] 0 0
Istanbul
Country [43] 0 0
Turkey
State/province [43] 0 0
Kocaeli
Country [44] 0 0
Turkey
State/province [44] 0 0
Mersin
Country [45] 0 0
Turkey
State/province [45] 0 0
Trabzon
Country [46] 0 0
Ukraine
State/province [46] 0 0
Crimean Regional Governmenta
Country [47] 0 0
Ukraine
State/province [47] 0 0
Kharkiv Governorate
Country [48] 0 0
Ukraine
State/province [48] 0 0
KIEV Governorate
Country [49] 0 0
Ukraine
State/province [49] 0 0
Podolia Governorate
Country [50] 0 0
Ukraine
State/province [50] 0 0
Kharkov
Country [51] 0 0
Ukraine
State/province [51] 0 0
Odesa

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A study to evaluate the efficacy and safety of fenebrutinib on disability progression in
adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible
participants will be randomized 1:1 to either daily oral fenebrutinib (or placebo) or
intravenous (IV) ocrelizumab (or placebo) in a blinded fashion through an interactive voice
or web-based response system (IxRS). Approximately 946 participants will be enrolled and will
be recruited globally. Participants who discontinue study medication early or discontinue
from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a
positive benefit-risk result in the Primary Analysis of the study.
Trial website
https://clinicaltrials.gov/show/NCT04544449
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GN41791 http://www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04544449