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

NCT05232825 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: CN42097
• Study Type: interventional
• Target: 236
• Locations: 8 countries
• Sites: 37

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

Outcome Measures

Primary Outcomes (1)

• Serum ocrelizumab area under the concentration-time curve (AUCW1-12)

  Day 1 to Week 12

Secondary Outcomes (7)

• 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

Study Arms (2)

Ocrelizumab: Intravenous (IV) formulation

ACTIVE COMPARATOR

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; Drug: Methylprednisolone IV; Drug: Diphenhydramine IV

Ocrelizumab: Subcutaneous (SC) formulation

EXPERIMENTAL

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; Drug: Dexamethasone given orally; Drug: Desloratadine given orally

Interventions

Ocrelizumab IV DRUG

IV Injection

Also known as: RO4964913

Ocrelizumab: Intravenous (IV) formulation

Ocrelizumab SC DRUG

SC Injection

Also known as: RO4964913

Ocrelizumab: Subcutaneous (SC) formulation

Methylprednisolone IV DRUG

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

Ocrelizumab: Intravenous (IV) formulation

Diphenhydramine IV DRUG

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

Ocrelizumab: Intravenous (IV) formulation

Dexamethasone given orally DRUG

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

Ocrelizumab: Subcutaneous (SC) formulation

Desloratadine given orally DRUG

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

Ocrelizumab: Subcutaneous (SC) formulation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (37)

Neurology Associates PA

Maitland, Florida, 32751, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis

Owosso, Michigan, 48867, United States

Location

UC Health Neurology

Dayton, Ohio, 45417, United States

Location

Premier Neurology

Greenville, South Carolina, 29605, United States

Location

Neurology Clinic PC

Cordova, Tennessee, 38018, United States

Location

CEDOES - Diagnóstico e Pesquisa

Vitória, Espírito Santo, 29055-450, Brazil

Location

Clinica Amo - Assistencia Medica Em Oncologia

Salvador, Estado de Bahia, 41950640, Brazil

Location

Fakultni nemocnice u sv. Anny

Brno, 656 91, Czechia

Location

Charles University, Medical faculty, Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Nemocnice Jihlava

Jihlava, 58633, Czechia

Location

Fakultni nemocnice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

Pardubicka Krajska Nemocnice

Pardubice, 532 03, Czechia

Location

Fakultni poliklinika VFN

Prague, 128 08, Czechia

Location

Fakultni nemocnice Motol

Prague, 150 06, Czechia

Location

Krajska zdravotni a.s Nemocnice Teplice o.z.

Teplice, 415 01, Czechia

Location

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

Rome, Lazio, 00133, Italy

Location

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, 00189, Italy

Location

Ospedale Civile di Montichiari

Montichiari, Lombardy, 25018, Italy

Location

IRCCS Istituto Neurologico Neuromed

Pozzilli, Molise, 86077, Italy

Location

Optimal Clinical Trials

Auckland, 1010, New Zealand

Location

Hawkes Bay Hospital

Hastings, 4120, New Zealand

Location

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, 85-796, Poland

Location

Care Clinic

Katowice, 40-568, Poland

Location

Centrum Neurologii Krzysztof Selmaj

Lodz, 90-324, Poland

Location

Przychodnia EuroMediCare

Wroc?aw, 50-220, Poland

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41071, Spain

Location

Complejo Hospitalario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, Tenerife, 38010, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14011, Spain

Location

Bakirkoy State Mental Hospital

Istanbul, 34000, Turkey (Türkiye)

Location

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi

Istanbul, 34098, Turkey (Türkiye)

Location

Katip Celebi University Ataturk Training and Research Hospital

Izmir, 35360, Turkey (Türkiye)

Location

Kocaeli University Hospital

Kocaeli, 41380, Turkey (Türkiye)

Location

Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi

Süleymanpa?a, 59100, Turkey (Türkiye)

Location

Related Publications (2)

• 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.

  PMID: 40245351 DERIVED

• 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.

  PMID: 39460719 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: February 10, 2022
• Study Start: May 3, 2022
• Primary Completion: March 10, 2023
• Study Completion: June 6, 2025
• Last Updated: August 6, 2025

Record last verified: 2025-08

Locations

PL (4); ES (5); IT (4); BR (2); CZ (8); US (7); TU (5); NZ (2)