Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Participants With Relapsing Multiple Sclerosis (RMS) or Primary Progressive Multiple Sclerosis (PPMS)

• Register: ClinicalTrials.gov
• Last refreshed on: 11 September 2023
• Main ID: NCT02688985
• Date of registration: 18/02/2016
• Prospective Registration: Yes
• Primary sponsor: Genentech, Inc.
• Public title: Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Participants With Relapsing Multiple Sclerosis (RMS) or Primary Progressive Multiple Sclerosis (PPMS)
• Scientific title: An Open-Label, Multicenter, Biomarker Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Patients With Relapsing Multiple Sclerosis or Primary Progressive Multiple Sclerosis
• Date of first enrolment: April 29, 2016
• Target sample size: 132
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02688985
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Canada, Germany, Sweden, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

General Inclusion Criteria:

- 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 percent (%) 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 Participants:

- Diagnosis of RMS in accordance with the 2010 revised McDonald criteria

- Expanded Disability Status Scale (EDSS) score of 0 to 5.5 points, inclusive, at
Screening

- Disease duration from the onset of multiple sclerosis symptoms less than (<) 15 years
in participants with an EDSS score greater than (>) 5.0 at Screening

- Either treatment-naive or receiving treatment with disease-modifying therapies,
including prior use of interferon (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 Gadolinium (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 Participants:

- 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 The treating
and/or study physician must agree that the participant is eligible to remain on the
same dose and regimen of their current standard of care at Screening, or to receive no
treatment if the participant is treatment-naïve, for 12 weeks after study enrollment

Inclusion Criteria Specific to PPMS Participants:

- 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 multiple sclerosis symptoms <10 years in
participants with an EDSS at Screening less than or equal to (
- Documented history of either elevated immunoglobulin G (IgG) Index or one or more IgG
oligoclonal bands (OCBs) detected by isoelectric focusing

Exclusion Criteria:

- Diagnosis of secondary progressive multiple sclerosis without relapses for at least 1
year

- History or known presence of recurrent or chronic infection (e.g., human
immunodeficiency virus [HIV], syphilis, tuberculosis)

- History of recurrent aspiration pneumonia requiring antibiotic therapy

- History of cancer, including solid tumors and hematological malignancies (except basal
cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the
cervix of the uterus that have been excised and resolved with documented clean margins
on pathology)

- 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 (including cardiac arrhythmia), pulmonary (including
chronic obstructive pulmonary disease), renal, hepatic, endocrine, gastrointestinal,
or any other significant disease

- Congestive heart failure (according to New York Heart Association III or IV functional
severity)

- Known active bacterial, viral, fungal, mycobacterial infection, or any major episode
of infection requiring hospitalization or treatment with IV antibiotics

- Any concomitant disease that may require chronic treatment with systemic
corticosteroids or immunosuppressants during the course of the study

- Contraindications or intolerance to oral or IV corticosteroids, including IV
methylprednisolone, according to the country label

- Contraindication for LP

- Previous treatment with B cell-targeted therapies (such as rituximab, ocrelizumab,
atacicept, belimumab, or ofatumumab)

- 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 a live vaccine within 6 weeks prior to enrollment

- Systemic corticosteroid therapy within 4 weeks prior to Baseline

- Previous or concurrent treatment with any investigational agent or treatment with any
experimental procedure for multiple sclerosis (such as treatment for chronic
cerebrospinal venous insufficiency)

- Certain laboratory abnormalities or findings at Screening

- Inability to complete an MRI

- Lack of peripheral venous access

- Pregnant or lactating, or intending to become pregnant during the study

Exclusion Criteria Specific to RMS Participants:

- Diagnosis of PPMS or secondary progressive multiple sclerosis without relapses



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Relapsing Multiple Sclerorsis

Multiple Sclerosis, Primary Progressive

Intervention(s)

Procedure: Lumbar Puncture

Drug: Antihistamine

Drug: Methyloprednisolone

Drug: Ocrelizumab

Primary Outcome(s)

Change in Number of CD19+ B cells in CSF from Treatment Baseline to Post-Treatment with Ocrelizumab [Time Frame: From Baseline to post-treatment (Week 12, 24, 52, 144, or 240 according to randomization)]

Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab [Time Frame: From Baseline to post-treatment (Week 12, 24, 52, 144, or 240 according to randomization)]

Change in Levels of NfL in CSF from Treatment Baseline to Post-Treatment with Ocrelizumab [Time Frame: From Baseline to post-treatment (Week 12, 24, 52, 144, or 240 according to randomization)]

Secondary ID(s)

2015-004616-37

ML29966

Source(s) of Monetary Support

Please refer to primary and secondary sponsors