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Tolerability and Safety of Switching From Rituximab to Ocrelizumab in Patients With Relapsing Forms of Multiple Sclerosis

This study is not yet open for participant recruitment.
Verified December 2016 by University of Colorado, Denver
Sponsor:
ClinicalTrials.gov Identifier:
NCT02980042
First Posted: December 2, 2016
Last Update Posted: December 6, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
University of Colorado, Denver
  Purpose
This is a prospective between and within group observational study to determine differences in tolerability, immunogenicity and safety related outcomes for 100 multiple sclerosis (MS) patients who have been administered at least two infusions of rituximab, six months apart and are willing to be switched to ocrelizumab compared to a 100 patients who are continuing on rituximab as a comparison cohort from the clinic population treated as part of clinical care.

Condition Intervention Phase
Multiple Sclerosis Drug: Ocrelizumab Drug: Rituximab Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluating the Tolerability and Safety Profile of Switching From Rituximab to Ocrelizumab: A Real World Evaluation of Patients With Relapsing Forms of Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by University of Colorado, Denver:

Primary Outcome Measures:
  • Proportion of patients with > 1 infusion related reaction (IRR) across any of their infusions between the switching and comparator groups. [ Time Frame: Month 21 ]
    The investigators will report the proportion of patients with > 1 IRR across any of their infusions between the switching and comparator groups.

  • Difference in the total number of IRRs after each infusion of ocrelizumab [ Time Frame: Month 21 ]
    The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab.

  • Proportion of IRRs per infusion per patient in the switching group compared to the comparator group [ Time Frame: Month 21 ]
    We will compare the proportion of patients with an IRR following day 1 infusion versus the proportion of patients with an IRR at day 15 and month 6 infusions of ocrelizumab in the switching group.

  • Severity of IRRs following each infusion of ocrelizumab in the switching and comparator groups [ Time Frame: Month 21 ]
    The severity of IRRs will be assessed following each infusion of ocrelizumab in the switching and comparator group using the National Cancer Institute's Common Terminology for Adverse Events Scale.6 The frequency of each severity grade of IRR will be compared in a similar fashion .


Secondary Outcome Measures:
  • Treatment Induced Anti-Drug Antibodies [ Time Frame: Prior to Day 1 infusion, day 15 and 6 month infusions ]
    We will measure the number of patients who have treatment induced ADAs against rituximab and ocrelizumab prior to every ocrelizumab infusion (T0, T1, T2) and at the research termination visit (T3). This analysis will be performed by PPD Laboratories and Covance as a single batch at end of study for the switching group.

  • Changes in Treatment Efficiency (B Cell) [ Time Frame: Prior to Day 1 infusion, 6 month infusions, and 12 month research termination visit ]
    We will measure B cell depletion before each ocrelizumab infusion (T0, T1 and T2), by the clinical laboratories at the University of Colorado Hospital. We will measure the proportion of patients who are B cell depleted (CD-19+ and CD-20+) by the time of the next infusion and 6 months after the last infusion in the switching group.

  • Changes in Cytokine Profile [ Time Frame: Prior to and 4 hours after Day 1 infusion, day 15 infusion, 6 month infusion, 12 month research termination visit ]
    To better characterize infusion reactions and evaluate the contribution by either hypersensitivity reactions to ocrelizumab directly and/or by release of cytokines from dyeing CD20 positive cells, serum levels of cytokines will be evaluated. Cytokines will be measured using the MesoScale platform before and 4 hours after the start of each ocrelizumab infusion (T0,T1,T2,T3). Plasma samples will be analyzed using the V-PLEX Human Biomarker 40-Plex Kit.

  • Changes in Patient Reported Infusion Tolerance [ Time Frame: At the end of Day 1 infusion, day 15 and 6 month infusions ]
    A short patient reported outcome Likert scale describing the patient's experience to any IRR will be developed by the research team at RMMSC. This scale will be administered by the study coordinators at the end of each infusion. Scale items will measure patient responses to their perception and experience of IRRs.

  • Changes in Treatment Efficiency (T Cell) [ Time Frame: Prior to Day 1 infusion, 6 month infusions, and 12 month research termination visit ]
    We will measure T cell depletion before each ocrelizumab infusion (T0, T1 and T2), by the clinical laboratories at the University of Colorado Hospital.


Estimated Enrollment: 200
Study Start Date: January 2017
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: January 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Switching Group
600 mg of ocrelizumab will be administered as one 600-mg IV infusions at a scheduled interval of every 24 weeks. The first dose of ocrelizumab will be a split dose of 300 mg on day 1 and day 15 followed by 600 mg, six months later. Each ocrelizumab infusion should be given as a slow IV infusion over approximately 150 minutes (2.5 hours) for the 300-mg dose. Ocrelizumab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and ocrelizumab should be infused through a dedicated line.
Drug: Ocrelizumab
A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells
Other Name: Ocrevus
Active Comparator: Comparator Group
Standard of care rituximab doses are 1000 mg infusion given as first dose followed by 500mg (or 1000 mg if evidence of early B cell recovery) infusion every 6 months thereafter. Rituximab must not be administered as an IV push or bolus. Well-adjusted infusion pumps should be used to control the infusion rate, and rituximab should be infused through a dedicated line
Drug: Rituximab
A chimeric monoclonal antibody against CD20.
Other Name: Rituxan

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Switching group:

  • Current active patient of RMMSC
  • 18-65 years
  • Diagnosis of relapsing forms of MS
  • Completed > two doses of rituximab that were administered six months apart
  • Are receiving their current infusions of rituximab at the University of Colorado Outpatient Infusion Center
  • Have discussed the possibility of switching to ocrelizumab with their MS provider
  • Scheduled for their next dose of the study drug within < 6 months from their last rituximab infusion
  • Screened for Hepatitis B and C and TB within 2 years of first dose of ocrelizumab
  • A negative serum pregnancy test must be available for premenopausal women and for women <12 months after the onset of menopause, unless they have undergone surgical sterilization.
  • Women of childbearing potential must agree to use a "highly effective", hormonal form of contraception or two "effective" forms of non-hormonal contraception. Contraception must continue for the duration of study treatment and for at least three months after the last dose of study treatment
  • Are able to complete patient reported outcomes developed as English written scales.
  • Must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with local regulatory requirements

Comparator group:

  • Current active patient of RMMSC
  • 18-65 years
  • Diagnosis of relapsing forms of MS
  • Completed > two doses of rituximab that were administered six months apart as standard of care
  • Are receiving their current infusions of rituximab as standard of care at the University of Colorado Outpatient Infusion Center and will continue to do so
  • Are willing to be followed for up to two additional rituximab infusions during the study period as standard of care
  • Must be able and willing to give meaningful, written informed consent prior to participation in the trial, in accordance with local regulatory requirements

Exclusion Criteria:

Both groups:

  • Pregnant or lactating women
  • Hypersensitivity to trial medications
  • Hepatic Dysfunction (liver enzymes are 5 times greater than normal)
  • History of Congestive Heart Failure
  • Any history of a positive blood assay for Hepatitis B or C
  • Any history of TB or a positive Quantiferon Gold Assay
  • Concurrent use of immunosuppressant medications
  • Any history of immunodeficiency or other medical condition increasing risk of anti-CD 20 therapy.
  • No serious infection at the time of a scheduled study infusion.
  • Any medical, psychiatric or other condition that could result in the patient not being able to give fully informed consent, or to comply with the protocol requirements as determined by the investigator
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02980042


Contacts
Contact: Shane Curran-Hays, MS 303-724-8305 shane.curran-hays@ucdenver.edu
Contact: Brooke Valdez 303-724-2704 brooke.valdez@ucdenver.edu

Sponsors and Collaborators
University of Colorado, Denver
Investigators
Principal Investigator: Timothy Vollmer, MD University of Colorado, Denver
OverallOfficial: Kavita Nair, PhD University of Colorado, Denver
OverallOfficial: Enrique Alvarez, MD, PhD University of Colorado, Denver
  More Information

Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02980042     History of Changes
Other Study ID Numbers: 16-1354
First Submitted: November 9, 2016
First Posted: December 2, 2016
Last Update Posted: December 6, 2016
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents