A Study to Explore the Mechanism of Action of Ocrelizumab and B-cell Biology in Patients with Relapsing Multiple Sclerosis or Primary Progressive Multiple Sclerosis.

Phase 1

Conditions: - Relapsing multiple sclerosis (RMS)/Primary Progressive Multiple Sclerosis (PPMS)
MedDRA version: 20.1Level: PTClassification code 10028245Term: Multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
MedDRA version: 21.1Level: PTClassification code 10063401Term: Primary progressive multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2015-004616-37-DE

Lead Sponsor: GENENTECH Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 96

Inclusion Criteria

General Inclusion Criteria
- Age 18 - 55 years, inclusive
- For women of childbearing potential: agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraceptive methods
that result in a failure rate of < 1% per year during the treatment period
and for at least 24 weeks after the last dose of study treatment or until
their B cells have repleted, whichever is longer

Inclusion Criteria Specific to RMS Patients
- Diagnosis of RMS in accordance with the 2010 revised McDonald criteria
- Expanded Disability Status Scale (EDSS) score of 0 - 5.5 points, inclusive, at screening
- Disease duration less than 15 years in participants with an EDSS > 5.0 at screening
- Either treatment-naive or receiving treatment with disease-modifying therapies, including prior use of IFN-beta-1a (Avonex®, Rebif®), IFN-beta-1b (Betaseron®/Betaferon), or glatiramer acetate (Copaxone®)
- At least one clinically documented relapse in the past year and/or at least one T1-weighted Gd-enhancing lesion in the past year and/or at least one new T2 lesion in the past year at the time of enrollment

Inclusion Criteria Specific to RMS Cohort Arm 4
- Must meet inclusion criteria for the RMS cohort
- Separate signed Informed Consent Form for the RMS Delayed Time to
Start Control Arm (Arm 4)
- Must be willing to remain on the same dose and regimen of current
standard of care, or no treatment if treatment-naïve, for 12 weeks after
study enrollment
Inclusion Criteria Specific to primary progressive multiple sclerosis
(PPMS) Patients
- Diagnosis of PPMS in accordance with the 2010 revised McDonald
criteria
- EDSS score of 3.0 - 6.5 points, inclusive, at screening
- Disease duration from the onset of MS symptoms: Less than 10 years
in patients with an EDSS at screening = 5.0
- Documented history of at least one of the following laboratory findings
in CSF:
Elevated IgG Index
One or more IgG OCBs detected by isoelectric focusing
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 96
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

General Exclusion Criteria
- Diagnosis of primary progressive MS
- Diagnosis of secondary progressive MS (without relapses for at least 1 year)
- History or known presence of recurrent or chronic infection
- History of recurrent aspiration pneumonia requiring antibiotic therapy
- History of cancer
- History of or currently active primary or secondary immunodeficiency
- History of coagulation disorders
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- History of alcohol or other drug abuse within 24 weeks prior to enrollment
- Known presence or history of other neurologic disorders
- Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, or any other significant disease
- Congestive heart failure
- Known active bacterial, viral, fungal, mycobacterial infection, or other infection or any major episode of infection
- Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants
- Contraindications for, or intolerance to, oral or intravenous (IV) corticosteroids,
- Contraindication for lumbar puncture (LP)
- Previous treatment with B cell-targeted therapies
- Previous treatment with natalizumab (Tysabri®), alemtuzumab, anti-CD4 agents, cladribine, teriflunomide, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
- Treatment with fingolimod/Gilenya®, dimethyl fumarate/Tecfidera®, or similar treatment within 6 months prior to enrollment
- Receipt of live vaccine
- Systemic corticosteroid therapy within 4 weeks prior to baseline
- Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for MS
- Laboratory abnormalities or findings at screening
- Inability to complete Magnetic Resonance Image (MRI)
- Lack of peripheral venous access

Exclusion Criteria Specific to RMS Patients
- Diagnosis of PPMS or SPMS without relapses

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To understand the impact of ocrelizumab treatment on neurofilament light (NfL) as a biomarker of neuronal damage in cerebrospinal fluid (CSF)<br>• To assess the number of cluster of differentiation (CD)19+ B cells in CSF (cell number/microliter) before and after treatment with ocrelizumab<br>• To assess the number of CD3+ T cells in CSF (cell number/microliter) before and after treatment with ocrelizumab;Secondary Objective: • The safety objective for this study, including for the Long-Term Extension, is to evaluate the safety of ocrelizumab;Primary end point(s): 1. Change in levels of NfL in CSF from treatment baseline to post-treatment with ocrelizumab<br>2. Change in number of CD19+ B cells in CSF from treatment baseline to post-treatment with ocrelizumab<br>3. Change in number of CD3+ T cells in CSF from treatment baseline to post-treatment with ocrelizumab<br>;Timepoint(s) of evaluation of this end point: 1-3. Treatment baseline (Day 1) and Weeks 12, 24, and 52

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Changes in vital signs, physical findings and laboratory results<br>2. Incidence of AEs<br>3. AEs related to biomarker sample collection;Timepoint(s) of evaluation of this end point: 1-3 Up to 6.5 years

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