Evaluating the Efficacy and Safety of Transitioning Patients From Natalizumab to Ocrelizumab (OCTAVE)

The primary objective of this study is to assess the efficacy of Ocrelizumab (OCR) in Relapsing Multiple Sclerosis patients who have been previously treated with natalizumab (NTZ) by evaluating relapse rate, progression on MRI and disability progression.

Study Overview

• Status: Completed
• Conditions: Relapsing Remitting Multiple Sclerosis

Detailed Description

This is a multicenter, prospective, open-label, Phase IV clinical trial. Patients with relapsing forms of Multiple Sclerosis (MS), ages 18 to 65, who have received 12 or more continuous infusions of NTZ, and have been free of relapses, disability worsening or Magnetic Resonance Imaging (MRI) progression 6 months prior to the transition screening visit will be eligible for the study. After informed consent to participate has been obtained, the patient will have physical exam (PE), non-blinded Expanded Disability Status Scale (EDSS), MRI, Multiple Sclerosis Impact Scale (MSIS-29) and labs done for the screening visit to determine eligibility. Brain MRI with and without contrast will be performed with the standard MS protocol. MRIs will be performed with 3mm slice thickness with no gaps between slices. Patients will receive their first dose of OCR 4 to 6 weeks after the last dose of NTZ. Other baseline measures, including physical exam, EDSS, MSIS-29, and labs will be performed within 4 weeks of screening. Physical exam, non-blinded EDSS, and labs will be performed at month 3, month 6, month 9, and month 12. MSIS-29 will be performed at months 6 and 12. In addition, MRIs will be performed at months 3, 6, and 12.

• Study Type: Observational
• Enrollment (Actual): 34

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • RWJBarnabas Health
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence MS Center
  • Washington
    • Richland, Washington, United States, 99352
      • Kadlec Neuroscience Center
    • Seattle, Washington, United States, 98122
      • Multiple Sclerosis Center, Swedish Neuroscience Institute
    • Spokane, Washington, United States, 99208
      • Providence Multiple Sclerosis Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Male and female patients with relapsing forms of MS, ages 18 to 65, have received 12 or more continuous infusions of NTZ, and have been free of relapses, disability worsening or MRI progression 6 months prior to switching from NTZ to OCR therapy are eligible to participate.

Description

Inclusion Criteria:

• Able to understand the purpose and risk of the study and provide signed informed consent document.
• Must have received 12 or more consecutive monthly infusions of NTZ, and have had no evidence of on-NTZ disease activity (clinically or on MRI) for the 6 months prior to the screening visit.
• Naïve to OCR.
• No evidence, in the opinion of the investigators of significant cognitive limitation or psychiatric disorder that would interfere with the conduct of the study.
• EDSS of ≤ 6.0 at screening.
• Female patients of childbearing potential must practice effective contraception and continue contraception during the study.

Exclusion Criteria:

• History of primary or secondary progressive multiple sclerosis.
• Any mental condition of such that patient is unable to understand the nature, scope, and possible consequences of the study.
• Patients with a known history of hepatitis B, hepatitis C, tuberculosis, PML, or who are HIV positive.
• Any persistent or severe infection.
• Any malignancy within 5 years, except for basal or squamous cell skin lesions, which have been surgically excised, with no evidence of metastasis.
• Pregnancy or lactation.
• Significant or uncontrolled somatic disease or severe depression in the last year.
• Inability to complete an MRI.
• Previous treatment with B-cell targeted therapies.
• Current use of immunosuppressive medication.
• Patients who have had evidence of disease activity within the 6 months prior to screening. This includes MS relapse, or new or enlarging T2 lesions or Gd+ enhancing lesions, or disability progression.
• Patients with any significant comorbidity that in the opinion of the investigator, would interfere with participation in the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Ocrelizumab, OCREVUS; Patients eligible for this study will be receiving OCREVUS as part of their routine care for MS treatment, and undergo the standard monitoring tests and procedures for MS patients receiving treatment. In addition, they will complete the EDSS scale on 6 occasions over a 12-month period, and the MSIS-29 on three occasions during the 12 month period for research.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse Rate at 12 months	the proportion of relapse-free patients at month 12 after switching from NTZ to OCR	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse Rate at Months 3, 6, and 9	Proportion of relapse-free patients at months 3, 6, and 9	3, 6, and 9 months
Mean time to first relapse on OCR	Average time to first relapse	12 months
Change in the EDSS score from baseline to month 12	Average change in EDSS score	12 months
Change in MSIS-29 from baseline to months 6 and 12	Average change in MSIS-29 score	6 and 12 months
Proportion of patients that discontinued OCR	Proportion of patients that stop treatment with OCR for any reason	12 months

Collaborators and Investigators

• Sponsor: Providence Health & Services
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Kyle Smoot, MD, Providence Brain & Spine Institute

Publications and helpful links

Helpful Links

• Providence Brain & Spine Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Actual): October 10, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): February 4, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; MS; ocrelizumab; Tysabri; Natalizumab; OCREVUS
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: 2017000156

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes