A PHASE III MULTICENTER, RANDOMIZED, DOUBLE-BLIND,DOUBLE-DUMMY, PARALLEL-GROUP STUDY TO EVALUATETHE EFFICACY AND SAFETY OF FENEBRUTINIB COMPAREDWITH TERIFLUNOMIDE IN ADULT PATIENTS WITH RELAPSING MULTIPLE SCLEROSIS
- Conditions
- -G35 Multiple sclerosisMultiple sclerosisG35
- Registration Number
- PER-076-20
- Lead Sponsor
- F. HOFFMANN-LA ROCHE LTD.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 0
Patients must meet the following criteria for study entry:
- Signed Informed Consent Form
- Age 1855 years inclusive at time of signing the Informed Consent Form
- Ability to comply with the study protocol
- EDSS score of 05.5 at screening
- A diagnosis of RMS* in accordance with the revised 2017 McDonald Criteria (Thompson
et al. 2018) and one of the following:
a) At least two documented clinical relapses within the last 2 years or one documented
clinical relapse within 12 months of screening (but not within the 30 days prior to
screening)
b) Documented evidence of the presence of at least one T1Gd+ lesion on MRI in the
12 months prior to randomization.
* RMS may include aSPMS as defined by Lublin 2014.
- Neurologically stable for at least 30 days prior to randomization and baseline assessments
- Ability to complete the 9-HPT for each hand in 240 seconds
- Ability to perform the T25FWT
- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception, and agreement to refrain from donating
eggs.
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a
condom, and agreement to refrain from donating sperm.
See protocol for more detail.
Patients who meet any of the following criteria will be excluded from study entry:
- Disease duration of 10 years from the onset of symptoms and an EDSS score at
screening 2.0
- Pregnant or breastfeeding, or intending to become pregnant during the study or within 8
weeks (with ATEP) after the final dose of study drug
- Men intending to father a child during the study or within 8 weeks (with ATEP) after final
dose of study drug
- A diagnosis of PPMS or non-active SPMS
- 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)
- History of cancer, including hematologic malignancy and solid tumors, within 10 years of
screening
- Known presence of other neurological disorders.
- Evidence of clinically significant psychiatric, pulmonary, renal, hepatic (including Gilbert
syndrome), metabolic, gastrointestinal (GI), or cardiovascular disease (including
arrhythmias or QTc prolongation), or endocrine disease (including uncontrolled diabetes,
non-gallstone pancreatitis, or chronic pancreatitis) that, in the investigator’s opinion, would
preclude patient participation.
- Presence of the New York Heart Association Class III and Class IV criteria for congestive
heart failure.
- Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect
patient safety or interpretation of study results, including QT interval corrected through use
of Fridericia’s formula (QTcF) 440 ms demonstrated by at least two ECGs 30 minutes
apart.
- Current treatment with medications that are well known to prolong the QT interval at doses
that have a clinically meaningful effect on QT, as determined by the investigator
- History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias.
- Rare hereditary problems of galactose intolerance, total lactase deficiency, or
glucose-galactose malabsorption
- Hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum
albumin 3.0 g/dL
- Patients with severe renal impairment undergoing dialysis and/or estimated glomerular
filtration rate (eGFR) 60 mL/min/1.73 m2 (may be repeated if eGFR
4559 mL/min/1.73 m2).
- Severe hepatic disease impairment (Child-Pugh Class C).
- Patients with significantly impaired bone marrow function or significant anemia, leukopenia,
neutropenia or thrombocytopenia.
- Patients with significantly impaired bone marrow function or significant anemia, leukopenia,
neutropenia or thrombocytopenia.
- 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.
See protocol for more detail.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Time to onset of cCDP12, defined as the time from baseline to the first occurrence<br>of a progression event according to at least one of the following three criteria; must<br>be confirmed at a regularly scheduled visit that is at least 12 weeks after the initial<br>disability progression:<br>- An increase from baseline in EDSS score of 1.0 point in patients with a<br>baseline EDSS score of 5.5 or an increase of 0.5 points in patients with a<br>baseline EDSS score of  5.5 (confirmed disability progression [CDP])<br>− ≥ 20% increase from baseline in the T25FWT<br>− ≥ 20% increase from baseline in time to complete the 9-HPT.<br>Measure:Time to onset of cCDP12.<br>Timepoints:Throughout study.<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Time to onset of<br>composite 24-week<br>CDP<br>(cCDP24),according to<br>evaluation of study<br>doctor.<br>Measure:Time to onset of<br>composite 24-week<br>CDP (cCDP24)<br>Timepoints:Throughout study.<br>;<br>Outcome name:Time to onset of 12-week CDP (CDP12), defined as an increase from baseline in<br>EDSS score of ≥ 1.0 point in patients with a baseline EDSS score of ≤ 5.5 or an<br>increase ≥ 0.5 points in patients with a baseline EDSS score of > 5.5<br>Measure:Time to onset of 12-week CDP (CDP12)<br>Timepoints:Throughout study.<br>