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

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ClinicalTrials.gov Identifier: NCT02980042
Recruitment Status : Completed
First Posted : December 2, 2016
Results First Posted : January 14, 2020
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
University of Colorado, Denver

Brief Summary:
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 or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Ocrelizumab Drug: Rituximab Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 200 participants
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
Actual Study Start Date : January 1, 2017
Actual Primary Completion Date : May 30, 2019
Actual Study Completion Date : May 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Proportion of Infusions With >= 1 IRR Between the Switching and Comparator Groups [ Time Frame: Day 1, Day 15, Week 24 ]
    The investigators will report the proportion of infusions with >= 1 IRR (infusion-related reaction) between the switching and comparator groups. Data was collected at Day 1, Day 15, and Week 24 and combined to determine the overall proportion of IRRs over the life of the study.

  2. Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group. [ Time Frame: Pre-study (Enrollment), Day 1, Day 15, Week 24 ]
    The investigators will report the difference in the total number of IRRs after each infusion of ocrelizumab compared to combined rituximab infusions in the comparator group.

  3. Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions [ Time Frame: Day 1, pre-study infusions ]
    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 (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .

  4. Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions [ Time Frame: Day 15, pre-study infusions ]
    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 (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion.

  5. Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups Infusions [ Time Frame: Week 24, pre-study infusions ]
    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 (Grades range from 1-5, with higher Grades indicating more severe reactions). The frequency of each severity grade of IRR will be compared in a similar fashion .

  6. Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions [ Time Frame: Day 1, Day 15, Week 24 ]
    We will also 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



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.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older 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 with the last dose having been administered:

    1. Within 12 months of screening and
    2. At least 6 months prior to the first planned infusion of study drug
  • 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
  • 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 with the last dose having been administered within 12 months of screening 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

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


Locations
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United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
Investigators
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Principal Investigator: Timothy Vollmer, MD University of Colorado, Denver
Principal Investigator: Kavita Nair, PhD University of Colorado, Denver
Principal Investigator: Enrique Alvarez, MD, PhD University of Colorado, Denver
  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:

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Responsible Party: University of Colorado, Denver
ClinicalTrials.gov Identifier: NCT02980042    
Other Study ID Numbers: 16-1354
First Posted: December 2, 2016    Key Record Dates
Results First Posted: January 14, 2020
Last Update Posted: January 14, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Ocrelizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents