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 1, 2020
• Last Update Posted: June 29, 2020
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Ocrelizumab Dose 1; Drug: Ocrelizumab Dose 2 and Dose 3	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 141 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 14, 2018
• Actual Primary Completion Date: May 31, 2019
• Actual Study Completion Date: May 31, 2019

Arms and Interventions

Arm	Intervention/treatment
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.	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
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.	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.

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Colorado

University of Colorado; Anschutz Medical Campus Department of Neurology

Aurora, Colorado, United States, 80045

United States, Massachusetts

Dragonfly Research, LLC

Wellesley, Massachusetts, United States, 02481

United States, Ohio

Cleveland Clinic Fndn

Cleveland, Ohio, United States, 44195

Ohio Health Research Institute Grant Medical Center

Columbus, Ohio, United States, 43215

United States, Oklahoma

Oklahoma Medical Research Foundation; MS Center of Excellence

Oklahoma City, Oklahoma, United States, 73104

Sponsors and Collaborators

Genentech, Inc.

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Genentech, Inc.:

Study Protocol  [PDF] June 6, 2018

Statistical Analysis Plan  [PDF] June 26, 2019

More Information

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT03606460
• Other Study ID Numbers: ML40638
• First Posted: July 30, 2018
• Results First Posted: June 1, 2020
• Last Update Posted: June 29, 2020
• Last Verified: June 2020

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

Additional relevant MeSH terms:

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; Ocrelizumab; Immunologic Factors; Physiological Effects of Drugs