A Phase III, Non-Inferiority, Randomized, Open-Label, Parallel Group, Multicenter Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis (Ocarina II)

July 17, 2026 updated by: Hoffmann-La Roche

A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis

This study will evaluate the pharmacokinetics, pharmacodynamics, safety, immunogenicity, and radiological and clinical effects of subcutaneous (SC) administration of ocrelizumab compared with the intravenous (IV) infusion of ocrelizumab in patients with either relapsing multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

236

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • Espírito Santo
      • Vitória, Espírito Santo, Brazil, 29055-450
        • CEDOES - Diagnóstico e Pesquisa
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41950640
        • Clinica Amo Assistencia Medica Em Oncologia
  • Czechia
      • Brno, Czechia, 656 91
        • Fakultni nemocnice u sv. Anny
      • Hradec Králové, Czechia, 500 05
        • Charles University, Medical faculty, Hradec Kralove
      • Jihlava, Czechia, 58633
        • Nemocnice Jihlava
      • Ostrava-Poruba, Czechia, 708 52
        • Fakultni Nemocnice Ostrava
      • Pardubice, Czechia, 532 03
        • Pardubicka Krajska Nemocnice
      • Prague, Czechia, 150 06
        • Fakultni nemocnice Motol
      • Prague, Czechia, 128 08
        • Fakultni poliklinika VFN
      • Teplice, Czechia, 415 01
        • Krajska zdravotni a.s Nemocnice Teplice o.z.
  • Italy
    • Lazio
      • Rome, Lazio, Italy, 00189
        • Azienda Ospedaliera Sant'Andrea
      • Rome, Lazio, Italy, 00133
        • Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
    • Lombardy
      • Montichiari, Lombardy, Italy, 25018
        • Ospedale Civile di Montichiari
    • Molise
      • Pozzilli, Molise, Italy, 86077
        • IRCCS Istituto Neurologico Neuromed
  • New Zealand
      • Auckland, New Zealand, 1010
        • Optimal Clinical Trials
      • Hastings, New Zealand, 4120
        • Hawkes Bay Hospital
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Neurocentrum Bydgoszcz sp. z o.o
      • Katowice, Poland, 40-568
        • CaRe Clinic
      • Lodz, Poland, 90-324
        • Centrum Neurologii Krzysztof Selmaj
      • Wroc?aw, Poland, 50-220
        • Przychodnia EuroMediCare
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Córdoba, Spain, 14011
        • Hospital Universitario Reina Sofia
    • Madrid
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro Majadahonda
    • Sevilla
      • Seville, Sevilla, Spain, 41071
        • Hospital Universitario Virgen Macarena
    • Tenerife
      • Santa Cruz de Tenerife, Tenerife, Spain, 38010
        • Complejo Hospitalario Nuestra Señora de la Candelaria
  • Turkey (Türkiye)
      • Istanbul, Turkey (Türkiye), 34000
        • Bakirkoy State Mental Hospital
      • Istanbul, Turkey (Türkiye), 34098
        • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi
      • Izmir, Turkey (Türkiye), 35360
        • Katip Celebi University Ataturk Training and Research Hospital
      • Kocaeli, Turkey (Türkiye), 41380
        • Kocaeli University Hospital
      • Süleymanpa?a, Turkey (Türkiye), 59100
        • Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi
  • United States
    • Florida
      • Maitland, Florida, United States, 32751
        • Neurology Associates PA
      • Tampa, Florida, United States, 33612
        • University of South Florida
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hospital
    • Michigan
      • Owosso, Michigan, United States, 48867
        • Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
    • Ohio
      • Dayton, Ohio, United States, 45417
        • UC Health Neurology
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Premier Neurology
    • Tennessee
      • Cordova, Tennessee, United States, 38018
        • Neurology Clinic PC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of PPMS or RMS according to the revised McDonald 2017 criteria (Thompson et al. 2018)
  • EDSS score, 0-6.5, inclusive, at screening
  • Neurological stability for ≥30 days prior to both screening and baseline
  • Disease duration from onset of MS symptoms of less than 15 years for patients with EDSS score <2.0 at screening
  • For females participants, without reproductive potential may be enrolled if post-menopausal, unless receiving a hormonal therapy for menopause or if surgically sterile
  • For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods

Exclusion Criteria:

  • Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV anti microbials within 8 weeks prior to and during screening or treatment with oral anti microbials 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
  • Receipt of a live-attenuated vaccine within 6 weeks prior to randomization Influenza vaccination is permitted if the inactivated vaccine formulation is administered
  • Inability to complete an MRI or contraindication to gadolinium administration
  • Contraindications to mandatory premedications for IRRs, including closed-angle glaucoma for antihistamines
  • Known presence of other neurologic disorders
  • 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, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude patient from participating in the study
  • History of or currently active primary or secondary (non-drug-related) immunodeficiency
  • Pregnant or breastfeeding, or intending to become pregnant during the study and 6 or 12 months
  • Lack of peripheral venous access
  • History of alcohol or other drug abuse within 12 months prior to screening
  • Treatment with any investigational agent within 24 weeks prior to screening or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS (e.g., treatment for chronic cerebrospinal venous insufficiency)
  • Participants who have previously received anti-CD20s if the last treatment was less than 2 years before screening, and/or if B-cell count is below lower limit of normal, and/or the discontinuation of the treatment was due to safety reasons or lack of efficacy
  • Previous treatment with cladribine, atacicept, and alemtuzumab
  • Previous treatment with fingolimod, siponimod, ponesimod, or ozanimod within 6 weeks of baseline
  • Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
  • Previous treatment with natalizumab within 4.5 months of baseline
  • Treatment with mitoxantrone within 2 years prior to baseline visit or evidence of cardiotoxicity following mitoxantrone use or a cumulative lifetime dose of more than 60 mg/m2
  • Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label.
  • If the washout requirements are not described in the applicable local label, then the wash out period must be 5 times the half-life of the medication. The PD effects of the previous medication must also be considered when determining the required time for washout.
  • Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
  • Any previous history of transplantation or anti-rejection therapy
  • Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
  • Systemic corticosteroid therapy within 4 weeks prior to screening
  • Positive screening tests for active, latent, or inadequately treated hepatitis B
  • Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
  • Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ocrelizumab: Intravenous (IV) formulation
Participants will receive the first dose of ocrelizumab IV as two IV infusions given 14 days apart. The subsequent doses of study drug will be administered as SC injections. A minimum of 22 weeks should be kept between SC doses. Participants will undergo 96 weeks of study treatment.
Drug: Ocrelizumab IV
IV Injection
Other Names:
  • RO4964913
Drug: Methylprednisolone IV
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
Drug: Diphenhydramine IV
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
Experimental: Ocrelizumab: Subcutaneous (SC) formulation
Participants will receive the first dose of ocrelizumab SC as one SC injection at a dose which is expected to result in non-inferior exposure to ocrelizumab IV. The subsequent doses of study drug will be administered as SC injections. A minimum of 22 weeks should be kept between the first and second SC doses, and between subsequent SC doses. Participants will undergo 96 weeks of study treatment.
Drug: Ocrelizumab SC
SC Injection
Other Names:
  • RO4964913
Drug: Dexamethasone given orally
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection
Drug: Desloratadine given orally
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Serum Ocrelizumab Area Under the Concentration-Time Curve Over the First 12 Weeks (AUCW1-12) After SC Administration
Time Frame: Day 1 Week 1 to Week 12
Day 1 Week 1 to Week 12

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Serum Concentration (Cmax) of Ocrelizumab SC
Time Frame: Day 1 Week 1 to Week 24
Day 1 Week 1 to Week 24
Rate of Gadolinium-enhancing Lesions on T1-weighted (T1Gd+) Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) at Weeks 8 and 24
Time Frame: At Weeks 8 and 24

Radiologic evaluation for the total number of T1Gd+ lesions was performed using a standardized MRI at Weeks 8 and 24 to monitor central nervous system (CNS) lesions in participants with MS. Estimand variable (adjusted lesion rate) was modeled by a negative binomial regression that included treatment variable & was adjusted for covariates: baseline T1Gd+ lesion (present or not), geographical region (United States of America vs. Rest of the world).

EE = Efficacy-evaluable.
At Weeks 8 and 24
Rate of New or Enlarging T2 Lesions as Detected by Brain MRI at Weeks 12 and 24
Time Frame: At Weeks 12 and 24
Radiologic evaluation for the new or enlarging T2 lesions was performed using a standardized MRI at Weeks 12 and 24 to monitor CNS lesions in participants with MS. Estimand variable (adjusted lesion rate) was modeled by a negative binomial regression that included treatment variable & was adjusted for covariates: baseline T2 lesion count, geographical region (United States of America vs. Rest of the world).
At Weeks 12 and 24
Number of Participants With Adverse Events (AEs)
Time Frame: From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks)
Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab After SC or IV Administration
Time Frame: Up to 138.1 weeks
Participants who received ocrelizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following ocrelizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Up to 138.1 weeks
Number of Participants With ADAs to rHuPH20 After Ocrelizumab SC Administration
Time Frame: Up to 138.1 weeks
Ocrelizumab SC formulation is co-formulated with rHuPH20 at a concentration of 1000 units per milliliter (U/mL). Participants who received ocrelizumab SC were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following ocrelizumab SC exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants with a positive post-baseline sample has been reported here.
Up to 138.1 weeks
Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96
Time Frame: At Weeks 12, 24, 48, and 96
B-cells were assessed in fresh whole blood using flow cytometry. Percentages have been rounded off.
At Weeks 12, 24, 48, and 96

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 3, 2022

Primary Completion (Actual)

March 10, 2023

Study Completion (Actual)

June 6, 2025

Study Registration Dates

First Submitted

January 27, 2022

First Submitted That Met QC Criteria

January 31, 2022

First Posted (Actual)

February 10, 2022

Study Record Updates

Last Update Posted (Actual)

August 11, 2026

Last Update Submitted That Met QC Criteria

July 17, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CN42097

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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