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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04544449
Ethics application status
Date submitted
4/09/2020
Date registered
10/09/2020

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 matched to ocrelizumab
Treatment: Drugs - Placebo matched to fenebrutinib

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 matched to ocrelizumab
Participants will receive ocrelizumab-matching placebo.

Treatment: Drugs: Placebo matched to fenebrutinib
Participants will receive fenebrutinib-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 Magnetic Resonance Imaging (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 4.7 years
Secondary outcome [8] 0 0
Plasma Concentrations of Fenebrutinib at Specified Timepoints
Timepoint [8] 0 0
Up to 4.7 years
Secondary outcome [9] 0 0
Percent Change from Screening in Serum Neurofilament Light Chain (NfL) Levels
Timepoint [9] 0 0
Up to Week 120

Eligibility
Key inclusion criteria
* For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years
* A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018).
* Disability progression in the 12 months prior to screening.
* Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.
* Pyramidal functional subscore >=2 at screening.
* For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for 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.
* Neurologically stable for at least 30 days prior to randomization and baseline assessments.
* 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) in <150 seconds.
* 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
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
* Any known or suspected active infection (excluding onychomycosis) at screening, including but not limited to a positive screening test 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. Exceptions: Basal/squamous cell carcinoma of skin cured by excision. In situ carcinoma of the cervix successfully treated by curative therapy >1 year prior to screening.
* 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.
* Presence of cirrhosis (Child-Pugh Class A, B, or C)
* 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 for 28 days 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.
* Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy
* Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed
* Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/10/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
18/12/2026
Actual
Sample size
Target
Accrual to date
Final
985
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Brain and Mind Research Institute - Camperdown
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
John Hunter Hospital - New Lambton
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [5] 0 0
Box Hill Hospital; Department of Neurology - Box Hill
Recruitment hospital [6] 0 0
Austin Hospital; Department of Neurology - Heidelberg
Recruitment hospital [7] 0 0
Royal Melbourne Hospital; Department of Neurology - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
2305 - New Lambton
Recruitment postcode(s) [4] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [5] 0 0
3128 - Box Hill
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
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United States of America
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Alabama
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California
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Samsun
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Trabzon
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Van
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Çankaya
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Ukraine
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Chernihiv Governorate
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Lutsk
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Odesa
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London
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Nottingham
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Swansea

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04544449