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)

• ClinicalTrials.gov Identifier: NCT03606460
• Recruitment Status: Completed
• First Posted: July 30, 2018
• Results First Posted: June 29, 2020
• Last Update Posted: June 29, 2020
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: July 23, 2018
• First Posted Date: July 30, 2018
• Results First Submitted Date: May 12, 2020
• Results First Posted Date: June 29, 2020
• Last Update Posted Date: June 29, 2020
• Actual Study Start Date: September 14, 2018
• Actual Primary Completion Date: May 31, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 12, 2020)

Percentage of Participants With Infusion-related Reaction (IRR) Treated With 600 mg IV Ocrelizumab [ Time Frame: During or within 24 hours of administration ]

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

Original Primary Outcome Measures (submitted: July 23, 2018)

Percentage of Participants With Adverse Events (AE) Treated With 600 mg IV Ocrelizumab [ Time Frame: 8 Weeks ]

This outcome measure will evaluate 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

Current Secondary Outcome Measures (submitted: June 12, 2020)

• Percentage of Participants With IRRs [ Time Frame: During or within 24 hours of administration ]
  This outcome measure evaluates the occurrence of overall IRRs with ocrelizumab either 300mg or 600mg IV infusion. Rate and frequency of NCI CTCAE v4.0 Grade 1-4 IRRs.
• Percentage of Participants With IRRs Treated With the 300 mg Shorter Dose of Ocrelizumab [ Time Frame: During or within 24 hours of administration ]
  This outcome measure evaluate the occurrence of severe IRRs with ocrelizumab 300 mg administered over the course of 1.5 hours. Rate and frequency of NCI CTCAE v4.0 Grade 3-4 IRRs.

Original Secondary Outcome Measures (submitted: July 23, 2018)

• Percentage of Participants With AEs [ Time Frame: 8 Weeks ]
  This outcome measure will evaluate the occurrence of overall IRRs with ocrelizumab administered per a shorter infusion protocol for both cohorts. Rate and frequency of NCI CTCAE v4.0 Grade 1-4 IRRs
• Percentage of Participants With AEs Treated With the 300 mg Shorter Dose of Ocrelizumab [ Time Frame: 8 Weeks ]
  This outcome measure will evaluate the occurrence of overall IRRs with ocrelizumab administered per a shorter infusion protocol for both cohorts. Rate and frequency of NCI CTCAE v4.0 Grade 3-4 IRRs

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• Official Title: A Phase IIIb, Open-Label Study To Evaluate The Safety And Tolerability Of Shorter Infusions Of Ocrelizumab In Patients With Primary Progressive And Relapsing Multiple Sclerosis
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

• Drug: Ocrelizumab Dose 1
  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.
• Drug: Ocrelizumab Dose 2 and Dose 3
  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

Study Arms

• Experimental: Cohort 1
  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.
  Intervention: Drug: Ocrelizumab Dose 2 and Dose 3
• Experimental: Cohort 2
  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.
  Intervention: Drug: Ocrelizumab Dose 1

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2020): 141
• Original Estimated Enrollment (submitted: July 23, 2018): 150
• Actual Study Completion Date: May 31, 2019
• Actual Primary Completion Date: May 31, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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
• Systemic corticosteroid therapy within 4 weeks prior to enrollment
• Contraindications to or intolerance of oral or IV corticosteroids, including IV methylprednisolone (or equivalent steroid) administered according to the country label
• Treatment with alemtuzumab
• Treatment with a B-cell targeted therapies other than ocrelizumab
• Treatment with a drug that is experimental
• Abnormal laboratory results per local laboratory standards and investigator assessment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03606460
• Other Study ID Numbers: ML40638
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Genentech, Inc.
• Study Sponsor: Genentech, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: June 2020