Safety of Switching From Rituximab to Ocrelizumab in MS Patients

NCT02980042 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 16-1354
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (6)

• Proportion of Infusions With >= 1 IRR Between the Switching and Comparator Groups

  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.

  Day 1, Day 15, Week 24

• Difference in the Total Number of IRRs After Each Infusion of Ocrelizumab Compared to Rituximab Infusions in the Comparator Group.

  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.

  Pre-study (Enrollment), Day 1, Day 15, Week 24

• Severity of IRRs Following the Day 1 Infusion of Ocrelizumab in the Switching and the Comparator Groups 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 .

  Day 1, pre-study infusions

• Severity of IRRs Following the Day 15 Infusion of Ocrelizumab in the Switching and the Comparator Groups 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.

  Day 15, pre-study infusions

• Severity of IRRs Following the Week 24 Infusion of Ocrelizumab in the Switching and the Comparator Groups 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 .

  Week 24, pre-study infusions

• Proportion of Patients With an IRR at Day 1 Versus Day 15 and Week 24 Infusions

  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.

  Day 1, Day 15, Week 24

Secondary Outcomes (35)

• Presence of Ocrelizumab Anti-drug Anti-bodies

  Day 1 and Week 24

• Presence of Rituximab Anti-drug Anti-bodies

  Day 1 and Week 24

• B Cell Depletion (CD19)

  Day 1, Week 24, 1 Year

• B Cell Depletion (CD20)

  Day 1, Week 24, 1 Year

• Cytokine: Eotaxin - Pre-Post Infusion - Day 1

  Day 1

Study Arms (2)

Switching Group

EXPERIMENTAL

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

Comparator Group

ACTIVE COMPARATOR

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

Interventions

Ocrelizumab DRUG

A humanized monoclonal antibody that targets CD20 and selectively depleted CD-20 expressing B cells

Also known as: Ocrevus

Switching Group

Rituximab DRUG

A chimeric monoclonal antibody against CD20.

Also known as: Rituxan

Comparator Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Switching group:
• Current active patient of RMMSC
• years
• Diagnosis of relapsing forms of MS
• Completed ≥ two doses of rituximab with the last dose having been administered:
• Within 12 months of screening and
• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ocrelizumab; Rituximab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Timothy Vollmer
• Organization: University of Colorado Anschutz, Neurology Department

timothy.vollmer@ucdenver.edu

3037242187

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: December 2, 2016
• Study Start: January 1, 2017
• Primary Completion: March 6, 2019
• Study Completion: March 6, 2019
• Last Updated: July 21, 2021
• Results First Posted: January 14, 2020

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)