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

NCT ID: NCT05232825

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-03
• Study Completion Date: 2025-06-06

Brief 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 multiple sclerosis (PPMS).

Conditions

Relapsing Multiple Sclerosis; Primary Progressive Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Ocrelizumab IV

Intervention Type: DRUG

IV Injection

Methylprednisolone IV

Intervention Type: DRUG

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

Diphenhydramine IV

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Ocrelizumab SC

Intervention Type: DRUG

SC Injection

Dexamethasone given orally

Intervention Type: DRUG

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

Desloratadine given orally

Intervention Type: DRUG

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

Interventions

Ocrelizumab IV

IV Injection

Intervention Type: DRUG

Ocrelizumab SC

SC Injection

Intervention Type: DRUG

Methylprednisolone IV

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

Intervention Type: DRUG

Diphenhydramine IV

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

Intervention Type: DRUG

Dexamethasone given orally

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

Intervention Type: DRUG

Desloratadine given orally

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

Intervention Type: DRUG

Other Intervention Names

RO4964913; RO4964913

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Neurology Associates PA

Maitland, Florida, United States

University of South Florida

Tampa, Florida, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis

Owosso, Michigan, United States

UC Health Neurology

Dayton, Ohio, United States

Premier Neurology

Greenville, South Carolina, United States

Neurology Clinic PC

Cordova, Tennessee, United States

CEDOES - Diagnóstico e Pesquisa

Vitória, Espírito Santo, Brazil

Clinica Amo - Assistencia Medica Em Oncologia

Salvador, Estado de Bahia, Brazil

Fakultni nemocnice u sv. Anny

Brno, , Czechia

Charles University, Medical faculty, Hradec Kralove

Hradec Králové, , Czechia

Nemocnice Jihlava

Jihlava, , Czechia

Fakultni nemocnice Ostrava

Ostrava-Poruba, , Czechia

Pardubicka Krajska Nemocnice

Pardubice, , Czechia

Fakultni poliklinika VFN

Prague, , Czechia

Fakultni nemocnice Motol

Prague, , Czechia

Krajska zdravotni a.s Nemocnice Teplice o.z.

Teplice, , Czechia

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

Rome, Lazio, Italy

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, Italy

Ospedale Civile di Montichiari

Montichiari, Lombardy, Italy

IRCCS Istituto Neurologico Neuromed

Pozzilli, Molise, Italy

Optimal Clinical Trials

Auckland, , New Zealand

Hawkes Bay Hospital

Hastings, , New Zealand

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, , Poland

Care Clinic

Katowice, , Poland

Centrum Neurologii Krzysztof Selmaj

Lodz, , Poland

Przychodnia EuroMediCare

Wroc?aw, , Poland

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario Virgen Macarena

Seville, Sevilla, Spain

Complejo Hospitalario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, Tenerife, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Bakirkoy State Mental Hospital

Istanbul, , Turkey (Türkiye)

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Katip Celebi University Ataturk Training and Research Hospital

Izmir, , Turkey (Türkiye)

Kocaeli University Hospital

Kocaeli, , Turkey (Türkiye)

Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi

Süleymanpa?a, , Turkey (Türkiye)

Countries

United States; Brazil; Czechia; Italy; New Zealand; Poland; Spain; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 40245351 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39460719 (View on PubMed)

Other Identifiers

CN42097

Identifier Type: -

Identifier Source: org_study_id