A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of a New Subcutaneous Formulation of Ocrelizumab in Participants With Multiple Sclerosis (OCARINA 3)

A Phase 1b Multicenter, Non-randomized, Open-label Study to Investigate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Pharmacodynamics of Single Ascending Doses of a New Subcutaneous Formulation of Ocrelizumab in Patients With Multiple Sclerosis

The main purpose of this study is to evaluate the safety and tolerability of the ocrelizumab subcutaneous (SC) test formulation in participants with multiple sclerosis (MS). The study consists of two treatment phases: a dose-escalation and dose-continuation phase. Participants will receive single ascending doses of ocrelizumab SC during an initial dose-escalation phase, with the option to continue treatment with the selected dose of ocrelizumab SC in the dose-continuation phase.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Ocrelizumab Co-formulated With rHuPH20

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WN45319 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 81210-310
      • Active, not recruiting
      • Instituto de Neurologia de Curitiba
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01228-200
      • Active, not recruiting
      • Centro de Pesquisas Clinicas
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Recruiting
      • Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 14090
      • Active, not recruiting
      • Inovacion y Desarrollo en ciencias de la salud
• United Kingdom
  • Nottingham, United Kingdom, NG7 2UH
    • Active, not recruiting
    • Nottingham University Hospitals NHS Trust
  • Swansea, United Kingdom, SA6 6NL
    • Active, not recruiting
    • Morriston Hospital
• United States
  • California
    • Carlsbad, California, United States, 92011
      • Active, not recruiting
      • Profound Research, LLC
  • Florida
    • Maitland, Florida, United States, 32751
      • Active, not recruiting
      • Neurology Associates, PA
    • Tampa, Florida, United States, 33612
      • Active, not recruiting
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Active, not recruiting
      • Shepherd Center Inc.
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Active, not recruiting
      • John Hopkins University School of Medicine
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Active, not recruiting
      • Hope Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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

Exclusion Criteria:

• Participants who have previously received anti-cluster of differentiation 20 (CD20s) (including ocrelizumab) less than 2 years before screening
• Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with intravenous (IV) antimicrobials within 8 weeks prior to and during screening or treatment with oral antimicrobials within 2 weeks prior to and during screening
• History of confirmed or suspected progressive multifocal leukoencephalopathy (PML)
• History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
• Immunocompromised state
• 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 or gastrointestinal, or any other significant disease that may preclude participation in the study
• Lack of peripheral venous access
• Previous treatment with cladribine, atacicept, and alemtuzumab
• Previous treatment with fingolimod, siponimod, ponesimod, or ozanimod within 6 weeks of baseline
• Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
• Any previous history of transplantation or anti-rejection therapy
• Positive screening tests for active, latent, or inadequately treated hepatitis B
• Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ocrelizumab SC; Participants will receive single ascending doses of ocrelizumab SC, co-formulated with recombinant human hyaluronidase (rHuPH20) on Day 1 of the 24 week dose-escalation phase. Participants who opt to continue treatment in the dose continuation phase will receive ocrelizumab SC at a dose determined in the dose escalation phase, every 24 weeks (Q24W) for 144 weeks.	Drug: Ocrelizumab Co-formulated With rHuPH20; Participants will receive ocrelizumab co-formulated with rHuPH20, as a SC injection, per the schedule specified in the treatment arm.; Other Names: RO4964913; Ocrevus®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events (AEs)	Up to 168 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Ocrelizumab Serum Concentration at Specified Timepoints Following Single SC Administration	Up to 168 weeks
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) to Ocrelizumab	Up to 168 weeks
Number of Participants With Treatment-emergent ADAs to rHuPH20	Up to 168 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2024
• Primary Completion (Estimated): February 15, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: June 18, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Relapsing Remitting Multiple Sclerosis; Primary Progressive Multiple Sclerosis
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; ocrelizumab
• Other Study ID Numbers: WN45319; 2024-513639-26-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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