Clinical Trial: 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)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official 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

Brief Summary: This is an open-label, multicenter, biomarker study designed to be hypothesis-generating in order to better understand the mechanism of action of ocrelizumab and B-cell biology in RMS or PPMS. The study will be conducted in two cohorts i.e. RMS cohort (4 arm group) and PPMS cohort (one arm group). RMS cohort: Ocrelizumab will be administered as two intravenous (IV) infusions of 300 milligrams (mg) on Days 1 and 15. Subsequent doses will be given as single 600-mg infusions at Weeks 24 and 48. Participants will be randomized in 1:1:1 ratio to receive lumbar puncture (LP) post-treatment at Week 12, 24, or 52 following the first dose of ocrelizumab in three arm groups. A fourth RMS arm with delayed treatment start (Arm 4 [control group]) will not be a part of the randomization and will be recruited separately, wherein treatment with ocrelizumab will be delayed for 12 weeks from pre-treatment baseline. PPMS cohort: Ocrelizumab 600 mg will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks. Participants will receive a LP at the start of the study before dosing with ocrelizumab and second LP at Week 52 following the first dose of ocrelizumab.

Detailed Summary:
Sponsor: Genentech, Inc.

Current Primary Outcome:

  • Change From Baseline in Neurofilament Light (NfL) Levels in Cerebrospinal Fluid (CSF) Post-Treatment With Ocrelizumab [ Time Frame: From Baseline to post-treatment (Week 12, 24, or 52 according to randomization) ]
  • Change From Baseline in Number of Cluster of Differentiation (CD) 19+ B-Cells in CSF Post-Treatment with Ocrelizumab [ Time Frame: From Baseline to post-treatment (Week 12, 24, or 52 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, or 52 according to randomization) ]


Original Primary Outcome:

  • Change From Baseline in Neurofilament Light (NfL) Levels in Cerebrospinal Fluid (CSF) Post-Treatment With Ocrelizumab [ Time Frame: From baseline to 52 weeks ]
  • Change from baseline in CD19+ B cells in CSF post-treatment with ocrelizumab [ Time Frame: From baseline to 52 weeks ]
  • Change from Baseline in CD3+ T-Cells in CSF Post-Treatment with Ocrelizumab [ Time Frame: From baseline to 52 weeks ]


Current Secondary Outcome:

  • Percentage of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab [ Time Frame: Predose (Hour 0) on Day 1 of Weeks 1, 24, 48; early termination (up to Week 52); every 24 weeks after Week 48 dose for 48 weeks or until B-cell count returns to baseline value or to lower limit of normal range (up to 3.5 years overall) ]
  • Percentage of Participants With Adverse Events [ Time Frame: From baseline up to approximately 3.5 years ]
  • Serum Concentration of Ocrelizumab [ Time Frame: Predose (Hour 0) on Day 1 of Weeks 1,24,48; at Weeks 12, 52; at early termination (up to Week 52); every 24 weeks after Week 48 dose for 48 weeks or until B-cell count returns to baseline value or to lower limit of normal range (up to 3.5 years overall) ]
  • Ocrelizumab Levels in CSF [ Time Frame: Baseline up to Week 52 (detailed timeframe is provided in outcome description) ]
    RMS Cohort (Arms 1, 2, 3): predose (Hour 0) on Week 1 (baseline), at Weeks 12, 24, or 52 (according to randomization); RMS Cohort (Arm 4): Week -12 (pre-treatment baseline), predose (Hour 0) on Week 1 (treatment baseline), Week 12 (optional); PPMS Cohort: predose (Hour 0) on Week 1 (baseline) and Week 52.


Original Secondary Outcome:

Information By: Genentech, Inc.

Dates:
Date Received: February 18, 2016
Date Started: April 30, 2016
Date Completion: September 30, 2018
Last Updated: May 8, 2017
Last Verified: May 2017