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)

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: Relapsing Multiple Sclerosis; Primary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: Ocrelizumab IV; Drug: Methylprednisolone IV; Drug: Diphenhydramine IV; Drug: Ocrelizumab SC; Drug: Dexamethasone given orally; Drug: Desloratadine given orally

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 41950640
      • Clinica Amo - Assistencia Medica Em Oncologia
  • Espírito Santo
    • Vitoria, Espírito Santo, Brazil, 29055-450
      • CEDOES - Diagnóstico e Pesquisa
• 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
  • Praha, Czechia, 150 06
    • Fakultni nemocnice Motol
  • Praha 2, Czechia, 128 08
    • Fakultni Poliklinika VFN
  • Teplice, Czechia, 415 01
    • Krajska zdravotni a.s Nemocnice Teplice o.z.
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
    • Roma, Lazio, Italy, 00133
      • Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
  • Lombardia
    • Montichiari, Lombardia, 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
  • Cordoba, 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
  • Istanbul, Turkey, 34000
    • Bakirkoy State Mental Hospital
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi
  • Izmir, Turkey, 35360
    • Katip Celebi University Ataturk Training and Research Hospital
  • Kocaeli, Turkey, 41380
    • Kocaeli University Hospital
  • Süleymanpa?a, Turkey, 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

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

How is the study designed?

Design Details

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

Number of Arms

2

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 (AUCW1-12)	Day 1 to Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS	Day 1 to Week 12
Total number of T1Gd+ lesions as detected by brain MRI	Weeks 8 and 24
Total number of new or enlarging T2 lesions as detected by brain MRI	Weeks 12 and 24
Percentage of participants with Adverse Events	Day 1 to Week 48
Incidence of treatment-emergent antidrug antibodies to ocrelizumab after SC or IV administration	Day 1 to Week 48
Incidence of treatment-emergent antibodies to rHuPH20	Day 1 to Week 48
Proportion of participants achieving CD19+ B cell level ≤5 cells/uL	Day 1 to Week 48

Collaborators and Investigators

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

Study record dates

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 6, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• 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; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Chronic Progressive; Sleep Aids, Pharmaceutical; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Histamine Antagonists; Histamine Agents; Neurotransmitter Agents; Hypnotics and Sedatives; Protective Agents; Anti-Allergic Agents; Neuroprotective Agents; Antipruritics; Cholinergic Antagonists; Cholinergic Agents; Histamine H1 Antagonists; Histamine H1 Antagonists, Non-Sedating; Dexamethasone; Methylprednisolone; Diphenhydramine; Promethazine; Ocrelizumab; Desloratadine
• 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