A Study to Evaluate the Safety of Administering Ocrelizumab Per a Shorter Infusion Protocol in Participants With Primary Progressive Multiple Sclerosis (PPMS) and Relapsing Multiple Sclerosis (RMS)

NCT03606460 | Completed Phase 3 Results FDA Drug

• 1 other identifier: ML40638
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 5

Brief Summary

This study is an open-label, non-randomized study to evaluate rate and severity of infusion-related reactions (IRRs) of ocrelizumab infused over a shorter time period than the approved administration rate in participants with PPMS or RMS in the United States (U.S.). Participants will be enrolled into two cohorts. Cohort 1 will examine the effect of administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. This cohort will consist of patients who have already received one or two doses of ocrelizumab according to the approved infusion protocol (i.e., per the currently U.S. label) and have reported no serious IRRs and who will then receive the next infusion of ocrelizumab at a higher rate in order to deliver 600 mg over the course of approximately 2 hours. Cohort 2 will examine the effect of administering ocrelizumab per a shorter infusion protocol for the second infusion of Dose 1. This cohort will consist of ocrelizumab naïve patients who, after receiving Infusion 1/Dose 1 of ocrelizumab at the approved rate (300 mg over approximately 2.5 hours or longer) have no reported serious IRRs, will then receive the second 300-mg shorter infusion over approximately 1.5 hours.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Infusion-related Reaction (IRR) Treated With 600 mg IV Ocrelizumab

  This outcome measure evaluates the occurrence of severe infusion-related reaction (IRR) with ocrelizumab 600 mg intravenously (IV) administered over the course of 2 hours. Rate and frequency of NCI CTCAE v4.0 Grade 3 and 4 IRRs

  During or within 24 hours of administration

Secondary Outcomes (2)

• Percentage of Participants With IRRs

  During or within 24 hours of administration

• Percentage of Participants With IRRs Treated With the 300 mg Shorter Dose of Ocrelizumab

  During or within 24 hours of administration

Study Arms (2)

Cohort 1

EXPERIMENTAL

This cohort will examine the effect of administering ocrelizumab per a shorter infusion protocol for Dose 2 or Dose 3. Participants who have already received one or two doses of ocrelizumab according to the approved infusion protocol and have reported no serious infusion-related reactions (IRRs) will be enrolled. They will then receive the next infusion of ocrelizumab (Dose 2 or Dose 3) at a dosage of 600 milligram (mg) over the course of approximately 2 hours. Dose 2 is administered at Week 24, Dose 3 is administered at Week 48 after initial infusion.

Drug: Ocrelizumab Dose 2 and Dose 3

Cohort 2

EXPERIMENTAL

This cohort will examine the effect of administering ocrelizumab per a shorter infusion protocol for the second infusion of Dose 1. Ocrelizumab-naïve participants will be enrolled who, after receiving Dose 1 of ocrelizumab at the approved rate have no reported serious IRRs, will then receive the second 300-mg shorter infusion over approximately 1.5 hours.

Drug: Ocrelizumab Dose 1

Interventions

Ocrelizumab Dose 1 DRUG

300 mg infusion administered to ocrelizumab-naive participants per approved protocol (over approximately 2.5 hours or longer) as per standard of care followed by a second 300 mg shorter infusion over approximately 1.5 hours.

Cohort 2

Ocrelizumab Dose 2 and Dose 3 DRUG

600 mg infusion of ocrelizumab administered at a shorter rate (i.e. over the course of approximately 2 hours) at Week 24 and at Week 48

Cohort 1

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Eligible to receive ocrelizumab per the United States Package Insert (USPI)
• Able to comply with the study protocol, in the investigator's judgment
• Age 18-55 years, inclusive
• Have a diagnosis of PPMS or RMS, confirmed per the revised 2017 McDonald criteria
• Expanded Disability Status Scale (EDSS) score of 0 to 6.5, inclusive
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 6 months after the last dose of study treatment (per the USPI)

You may not qualify if:

• Experienced serious IRR(s)
• History of life-threatening infusion reaction to ocrelizumab
• Known presence of other neurological disorders
• Pregnancy or lactation, or intention to become pregnant during the study
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• Significant, uncontrolled disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine, and gastrointestinal or any other significant disease that may preclude patient from participating in the study
• Congestive heart failure
• Known active bacterial, viral, fungal, mycobacterial infection or other infection or any severe episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to baseline visit or oral antibiotics within 2 weeks prior to baseline visit
• History of or currently active primary or secondary immunodeficiency
• History or known presence of recurrent or chronic infection (e.g., HIV, syphilis, tuberculosis)
• History of recurrent aspiration pneumonia requiring antibiotic therapy
• History of malignancy, including solid tumors and hematological malignancies,except basal cell, in situ squamous cell carcinoma of the skin, and in situ carcinoma of the cervix of the uterus that have been excised with clear margins
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of alcohol or drug abuse within 24 weeks prior to enrollment
• Receipt of a live vaccine within 6 weeks prior to enrollment

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (5)

University of Colorado; Anschutz Medical Campus Department of Neurology

Aurora, Colorado, 80045, United States

Location

Dragonfly Research, LLC

Wellesley, Massachusetts, 02481, United States

Location

Cleveland Clinic Fndn

Cleveland, Ohio, 44195, United States

Location

Ohio Health Research Institute Grant Medical Center

Columbus, Ohio, 43215, United States

Location

Oklahoma Medical Research Foundation; MS Center of Excellence

Oklahoma City, Oklahoma, 73104, United States

Location

Related Publications (1)

• Vollmer TL, Cohen JA, Alvarez E, Nair KV, Boster A, Katz J, Pardo G, Pei J, Raut P, Merchant S, MacLean E, Pradhan A, Moss B. Safety results of administering ocrelizumab per a shorter infusion protocol in patients with primary progressive and relapsing multiple sclerosis. Mult Scler Relat Disord. 2020 Nov;46:102454. doi: 10.1016/j.msard.2020.102454. Epub 2020 Aug 18.

  PMID: 33045496 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 23, 2018
• First Posted: July 30, 2018
• Study Start: September 14, 2018
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: June 29, 2020
• Results First Posted: June 29, 2020

Record last verified: 2020-06

Locations

US (5)