G35 Multiple Sclerosis Multiple Sclerosis
Conditions
Interventions
None listed
Sponsors
F. HOFFMANN-LA ROCHE LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet the following criteria for study entry: - Signed Informed Consent Form - Age 18?55 years inclusive at time of signing the Informed Consent Form - Ability to comply with the study protocol - EDSS score of 0?5.5 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.
Exclusion criteria
Exclusion criteria: 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 45?59 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to onset of cCDP12, defined as the time from baseline to the first occurrence of a progression event according to at least one of the following three criteria; must be confirmed at a regularly scheduled visit that is at least 12 weeks after the initial disability progression: - An increase from baseline in EDSS score of ?1.0 point in patients with a baseline EDSS score of ?5.5 or an increase of ?0.5 points in patients with a baseline EDSS score of ? 5.5 (confirmed disability progression [CDP]) - = 20% increase from baseline in the T25FWT - = 20% increase from baseline in time to complete the 9-HPT. NAME OF THE RESULT: Time to onset of cCDP12. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to onset of cCDP12, defined as the time from baseline to the first occurrence of a progression event according to at least one of the following three criteria; must be confirmed at a regularly scheduled visit that is at least 12 weeks after the initial disability progression: - An increase from baseline in EDSS score of ?1.0 point in patients with a baseline EDSS score of ?5.5 or an increase of ?0.5 points in patients with a baseline EDSS score of ? 5.5 (confirmed disability progression [CDP]) - = 20% increase from baseline in the T25FWT - = 20% increase from baseline in time to complete the 9-HPT. NAME OF THE RESULT: Time to onset of cCDP12. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout study.;Time to onset of composite 24-week CDP (cCDP24),according to evaluation of study doctor. NAME OF THE RESULT: Time to onset of composite 24-week CDP (cCDP24) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout study.;Time to onset of 12-week CDP (CDP12), defined as an increase from baseline in EDSS score of = 1.0 point in patients with a baseline EDSS score of = 5.5 or an increase = 0.5 points in patients with a baseline EDSS score of > 5.5 NAME OF THE RESULT: Time to onset of 12-week CDP (CDP12) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Throughout study. | — |
Countries
Argentina, Belgium, Brazil, Canada, China, Czech Republic, Finland, France, Germany, Hong Kong, Hungary, Israel, Italy, Netherlands, Peru, Portugal, Russian Federation, Spain, Switzerland, Taiwan, Ukraine, United States
Outcome results
None listed