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Relapsing Multiple SclerosisPhase 3Ocarina IINCT05232825

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

A Phase 3 study testing Ocrelizumab IV, Ocrelizumab SC and Methylprednisolone IV in people with Relapsing Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by Hoffmann-La Roche at 37 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
Ocrelizumab IV, Ocrelizumab SC and Methylprednisolone IV
Could I receive a placebo?
No, everyone receives an active treatment
How many people
236 participants
Where
37 sitesin 8 countries
Study dates
3 May 2022to 6 Jun 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 30Show fewer
  • 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

Trial locations and contacts

37 sites in 8 countries.

37 sites in 8 countries

Czechia8 sites

  • Fakultni nemocnice u sv. Anny

    Brno, 656 91

  • Charles University, Medical faculty, Hradec Kralove

    Hradec Králové, 500 05

  • Nemocnice Jihlava

    Jihlava, 58633

  • Fakultni nemocnice Ostrava

    Ostrava-Poruba, 708 52

  • Pardubicka Krajska Nemocnice

    Pardubice, 532 03

  • Fakultni poliklinika VFN

    Prague, 128 08

  • Fakultni nemocnice Motol

    Prague, 150 06

  • Krajska zdravotni a.s Nemocnice Teplice o.z.

    Teplice, 415 01

Other trials in Czechia

United States7 sites

  • Johns Hopkins Hospital

    Baltimore, Maryland, 21287

  • Neurology Clinic PC

    Cordova, Tennessee, 38018

  • UC Health Neurology

    Dayton, Ohio, 45417

  • Premier Neurology

    Greenville, South Carolina, 29605

  • Neurology Associates PA

    Maitland, Florida, 32751

  • Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis

    Owosso, Michigan, 48867

  • University of South Florida

    Tampa, Florida, 33612

Other trials in United States

Spain5 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario Reina Sofia

    Córdoba, 14011

  • Hospital Universitario Puerta de Hierro Majadahonda

    Majadahonda, Madrid, 28222

  • Complejo Hospitalario Nuestra Señora de la Candelaria

    Santa Cruz de Tenerife, Tenerife, 38010

  • Hospital Universitario Virgen Macarena

    Seville, Sevilla, 41071

Other trials in Spain

Turkey (Türkiye)5 sites

  • Bakirkoy State Mental Hospital

    Istanbul, 34000

  • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi

    Istanbul, 34098

  • Katip Celebi University Ataturk Training and Research Hospital

    Izmir, 35360

  • Kocaeli University Hospital

    Kocaeli, 41380

  • Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi

    Süleymanpa?a, 59100

Other trials in Turkey (Türkiye)

Italy4 sites

  • Ospedale Civile di Montichiari

    Montichiari, Lombardy, 25018

  • IRCCS Istituto Neurologico Neuromed

    Pozzilli, Molise, 86077

  • Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla

    Rome, Lazio, 00133

  • Azienda Ospedaliera Sant'Andrea

    Rome, Lazio, 00189

Other trials in Italy

Poland4 sites

  • Neurocentrum Bydgoszcz sp. z o.o

    Bydgoszcz, 85-796

  • Care Clinic

    Katowice, 40-568

  • Centrum Neurologii Krzysztof Selmaj

    Lodz, 90-324

  • Przychodnia EuroMediCare

    Wroc?aw, 50-220

Other trials in Poland

Brazil2 sites

  • Clinica Amo Assistencia Medica Em Oncologia

    Salvador, Estado de Bahia, 41950640

  • CEDOES - Diagnóstico e Pesquisa

    Vitória, Espírito Santo, 29055-450

Other trials in Brazil

New Zealand2 sites

  • Optimal Clinical Trials

    Auckland, 1010

  • Hawkes Bay Hospital

    Hastings, 4120

Other trials in New Zealand

About this study

Official title: 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).

Being tested
Ocrelizumab IV, Ocrelizumab SC, Methylprednisolone IV, Diphenhydramine IV, Dexamethasone given orally
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ocrelizumab IVDrug

    Also called RO4964913

    IV Injection

  • Ocrelizumab SCDrug

    Also called RO4964913

    SC Injection

  • Methylprednisolone IVDrug

    Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion

  • Diphenhydramine IVDrug

    Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion

  • Dexamethasone given orallyDrug

    Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection

  • Desloratadine given orallyDrug

    Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection

Study groups in NCT05232825
Study groupRoleWhat they receive
Ocrelizumab: Intravenous (IV) formulationActive comparatorParticipants 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.
Receives: Drug: Ocrelizumab IV; Drug: Methylprednisolone IV; Drug: Diphenhydramine IV
Ocrelizumab: Subcutaneous (SC) formulationExperimentalParticipants 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.
Receives: Drug: Ocrelizumab SC; Drug: Dexamethasone given orally; Drug: Desloratadine given orally

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Serum Ocrelizumab Area Under the Concentration-Time Curve Over the First 12 Weeks (AUCW1-12) After SC Administration

    Measured: Day 1 Week 1 to Week 12

Secondary outcomes (7)

  1. Maximum Serum Concentration (Cmax) of Ocrelizumab SC

    Measured: Day 1 Week 1 to Week 24

  2. Rate of Gadolinium-enhancing Lesions on T1-weighted (T1Gd+) Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) 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.

    Measured: At Weeks 8 and 24

  3. Rate of New or Enlarging T2 Lesions as Detected by Brain MRI 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).

    Measured: At Weeks 12 and 24

  4. Number of Participants With Adverse Events (AEs)

    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.

    Measured: From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks)

  5. Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab After SC or IV Administration

    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.

    Measured: Up to 138.1 weeks

  6. Number of Participants With ADAs to rHuPH20 After Ocrelizumab SC Administration

    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.

    Measured: Up to 138.1 weeks

  7. Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96

    B-cells were assessed in fresh whole blood using flow cytometry. Percentages have been rounded off.

    Measured: At Weeks 12, 24, 48, and 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2022
  2. Study start3 May 2022
  3. Primary completion10 Mar 2023
  4. Study completion6 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
236 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05232825
Sponsor's protocol ID
CN42097
Acronym
Ocarina II
Status last verified
Jul 2026
First submitted
27 Jan 2022
Last updated
11 Aug 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Newsome SD, Krzystanek E, Selmaj KW, Dufek M, Goldstick L, Pozzilli C, Figueiredo C, Townsend B, Kletzl H, Bortolami O, Zecevic D, Giacobino C, Clinch S, Shen YA, Bhullar GD, Schneble HM, Centonze D. Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase 3 OCARINA II Study. Neurology. 2025 May 13;104(9):e213574. doi: 10.1212/WNL.0000000000213574. Epub 2025 Apr 17.

    PubMed 40245351

  • Newsome SD, Goldstick L, Robertson DS, Bowen JD, Naismith RT, Townsend B, Figueiredo C, Kletzl H, Giraudon M, Bortolami O, Zecevic D, Giacobino C, Clinch S, Shen YA, Deol-Bhullar G, Bermel RA. Subcutaneous ocrelizumab in multiple sclerosis: Results of the Phase 1b OCARINA I study. Ann Clin Transl Neurol. 2024 Dec;11(12):3215-3226. doi: 10.1002/acn3.52229. Epub 2024 Oct 26.

    PubMed 39460719

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ocrelizumab IV, Ocrelizumab SC and Methylprednisolone IV in people with Relapsing Multiple Sclerosis and Primary Progressive Multiple Sclerosis, run by Hoffmann-La Roche at 37 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in Czechia, United States, Spain, Turkey (Türkiye), Italy and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05232825, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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