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

NCT03972306 | Completed Phase 1 FDA Drug

• 1 other identifier: CN41144
• Study Type: interventional
• Target: 134
• Locations: 1 country
• Sites: 18

Brief Summary

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

Conditions

Multiple Sclerosis (MS)

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• 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)

Study Arms (4)

Group A: Cohorts A1-A4

EXPERIMENTAL

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; Drug: rHuPH20

Group A: Cohort A5

EXPERIMENTAL

In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.

Drug: Ocrelizumab; Drug: rHuPH20

Group A: Cohort AA

EXPERIMENTAL

Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion

Drug: Ocrelizumab

Group B: Cohorts B1-B4

EXPERIMENTAL

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; Drug: rHuPH20

Interventions

Ocrelizumab DRUG

Administered by subcutaneous Injection

Group A: Cohort A5; Group A: Cohorts A1-A4; Group B: Cohorts B1-B4

rHuPH20 DRUG

Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab

Group A: Cohort A5; Group A: Cohorts A1-A4; Group B: Cohorts B1-B4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (18)

University of Colorado

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

The NeuroMedical Clinic of Central Louisiana

Alexandria, Louisiana, 71301, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

John Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Wayne State University

Detroit, Michigan, 48201, United States

Location

Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis

Owosso, Michigan, 48867, United States

Location

Washington Univ School of Med

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cleveland Clinic Mellen Center

Cleveland, Ohio, 44195, United States

Location

UC Health Neurology

Dayton, Ohio, 45417, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Neurology Clinic PC

Cordova, Tennessee, 38018, United States

Location

University of Texas at Houston

Houston, Texas, 77030, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

MultiCare Health System Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ocrelizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: June 3, 2019
• Study Start: August 12, 2019
• Primary Completion: June 3, 2025
• Study Completion: June 3, 2025
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)