A Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Participants With Multiple Sclerosis

A Phase Ib, Open-Label, Multicenter Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Patients With Multiple Sclerosis

This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with multiple sclerosis (MS).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis (MS)
• Intervention / Treatment: Drug: Ocrelizumab; Drug: Ocrelizumab; Drug: rHuPH20

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • The NeuroMedical Clinic of Central Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
    • Owosso, Michigan, United States, 48867
      • Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington Univ School of Med
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Mellen Center
    • Dayton, Ohio, United States, 45417
      • UC Health Neurology
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas at Houston
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Primary Progressive Multiple Sclerosis (PPMS) or Relapsing Multiple Sclerosis (RMS) according to the revised McDonald 2017 criteria (Thompson et al. 2018)
• Expanded Disability Status Scale (EDSS) score, 0-6.5, inclusive, at screening
• Absence of relapses for 30 days prior to the screening visit
• For the dose escalation phase for participants pretreated with ocrelizumab (Group A):

treatment with IV ocrelizumab for at least 1 year prior to screening (i.e., at least two 600-mg doses of ocrelizumab separated by 24 weeks)

• For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab.
• For female perticipants without reproductive potential:

Women may be enrolled if post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy).

Exclusion Criteria:

• MS disease duration of more than 15 years for participants with an Expanded Disability Status Scale (EDSS) score <2.0 at screening.
• Known presence of other neurologic disorders that may mimic MS, including, but not limited to, the following:
• History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord
• History or known presence of Central Nervous System (CNS) or spinal cord tumor (e.g., meningioma,glioma)
• History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency)
• History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1, herpes zoster and myelopathy.
• History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke syndrome)
• Neuromyelitis optica
• History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren syndrome, Behçet disease, sarcoidosis).
• History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Cohorts A1-A4; Participants (participants pretreated with ocrelizumab) will receive a single injection of subcutaneous (SC) ocrelizumab co-mixed with rHuPH20 in the abdomen. For every new dose level, recruitment will be staggered by enrolling 1 participant in each cohort followed by a 48-hour waiting period to review safety and tolerability data by the Safety Monitoring Committee (SMC) prior to enrolling subsequent participants in the same cohort. Currently, the planned dose escalation steps for patients who enroll in Group A are as follows: Cohort A1: 40 mg of SC ocrelizumab; Cohort A2: 200 mg of SC ocrelizumab; Cohort A3: 600 mg of SC ocrelizumab; Cohort A4: 1200 mg of SC ocrelizumab	Drug: Ocrelizumab; Administered by subcutaneous Injection; Drug: Ocrelizumab; Administered by Intravenous (IV) Injection; Drug: rHuPH20; Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab
Experimental: Group A: Cohort A5; In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.	Drug: Ocrelizumab; Administered by subcutaneous Injection; Drug: Ocrelizumab; Administered by Intravenous (IV) Injection; Drug: rHuPH20; Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab
Experimental: Group A: Cohort AA; Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion	Drug: Ocrelizumab; Administered by subcutaneous Injection; Drug: Ocrelizumab; Administered by Intravenous (IV) Injection
Experimental: Group B: Cohorts B1-B4; Ocrelizumab treatment- naive participants will receive a minimum of 3 patients in Cohort B will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.; Cohort B1: 40 mg of SC ocrelizumab; Cohort B2: 200 mg of SC ocrelizumab; Cohort B3: 600 mg of SC ocrelizumab; Cohort B4: 1200 mg of SC ocrelizumab	Drug: Ocrelizumab; Administered by subcutaneous Injection; Drug: Ocrelizumab; Administered by Intravenous (IV) Injection; Drug: rHuPH20; Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration	At predefined intervals from baseline through end of study (approximately 5 years)
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration	At predefined intervals from baseline through end of study (approximately 5 years)
Percentage of participants with adverse events	Baseline to end of study (approximately 5 years)
Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters	Baseline to end of study (approximately 5 years)
Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS	Baseline to end of study (approximately 5 years)
Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA)	Baseline to end of study (approximately 5 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab	Baseline to end of study (approximately 5 years)
Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20	Baseline to end of study (approximately 5 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Actual): June 3, 2025
• Study Completion (Actual): June 3, 2025

Study Registration Dates

• First Submitted: May 29, 2019
• First Submitted That Met QC Criteria: May 31, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Immunologic Factors; Physiological Effects of Drugs; Ocrelizumab
• Other Study ID Numbers: CN41144

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No