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

Phase 3

Active, not recruiting

• Conditions: Relapsing Multiple Sclerosis; Primary Progressive Multiple Sclerosis
• Interventions: Drug: Ocrelizumab IV; Drug: Ocrelizumab SC; Drug: Dexamethasone given orally; Drug: Methylprednisolone IV; Drug: Desloratadine given orally; Drug: Diphenhydramine IV

• Registration Number: NCT05232825
• Lead Sponsor: Hoffmann-La Roche

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-27
• Study First Submitted QC: 2022-01-31
• Study First Posted: 2022-02-10
• Study Start: 2022-05-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-23
• Last Update Posted: 2024-12-27
• Primary Completion: 2025-04-01
• Study Completion: 2025-04-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 236

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ocrelizumab: Intravenous (IV) formulation	Ocrelizumab IV	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.
Ocrelizumab: Subcutaneous (SC) formulation	Dexamethasone given orally	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.
Ocrelizumab: Subcutaneous (SC) formulation	Ocrelizumab SC	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.
Ocrelizumab: Subcutaneous (SC) formulation	Desloratadine given orally	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.
Ocrelizumab: Intravenous (IV) formulation	Methylprednisolone IV	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.
Ocrelizumab: Intravenous (IV) formulation	Diphenhydramine IV	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.

Primary Outcome Measures

Name	Time	Method
Serum ocrelizumab area under the concentration-time curve (AUCW1-12)	Day 1 to Week 12

Secondary Outcome Measures

Name	Time	Method
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
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
Percentage of participants with Adverse Events	Day 1 to Week 48

Trial Locations

Locations (37)

Johns Hopkins Hospital; Neurology; 🇺🇸 Baltimore, Maryland, United States

Premier Neurology; 🇺🇸 Greenville, South Carolina, United States

UC Health Neurology; 🇺🇸 Dayton, Ohio, United States

Neurology Associates PA; 🇺🇸 Hickory, North Carolina, United States

Fakultni nemocnice u sv. Anny; Neurologicka klinika; 🇨🇿 Brno, Czechia

Neurology Clinic PC; 🇺🇸 Cordova, Tennessee, United States

Charles University, Medical faculty, Hradec Kralove ;Department of Neurology; 🇨🇿 Hradec Králové, Czechia

Clinica Amo - Assistencia Medica Em Oncologia; 🇧🇷 Salvador, BA, Brazil

Nemocnice Jihlava; NEU-Neurologicke oddeleni; 🇨🇿 Jihlava, Czechia

Pardubicka Krajska Nemocnice; Department of Neurology; 🇨🇿 Pardubice, Czechia

Fakultni nemocnice Ostrava; MS centrum; 🇨🇿 Ostrava-Poruba, Czechia

Fakultni nemocnice Motol; Neurologicka klinika; 🇨🇿 Praha, Czechia

Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla; 🇮🇹 Roma, Lazio, Italy

Krajska zdravotni a.s Nemocnice Teplice o.z.; RS centrum; 🇨🇿 Teplice, Czechia

Azienda Ospedaliera Sant'Andrea; UOC Neurologia; 🇮🇹 Roma, Lazio, Italy

IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla; 🇮🇹 Pozzilli, Molise, Italy

Hawkes Bay Hospital; 🇳🇿 Hastings, New Zealand

Neurocentrum Bydgoszcz sp. z o.o; 🇵🇱 Bydgoszcz, Poland

Centrum Neurologii Krzysztof Selmaj; 🇵🇱 Lodz, Poland

Przychodnia EuroMediCare; 🇵🇱 Wroc?aw, Poland

Hospital Universitario Virgen Macarena; 🇪🇸 Seville, Sevilla, Spain

Bakirkoy State Mental Hospital; 🇹🇷 Istanbul, Turkey

Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi; Noroloji; 🇹🇷 Süleymanpa?a, Turkey

Fakultni poliklinika VFN; RS centrum; 🇨🇿 Praha 2, Czechia

Optimal Clinical Trials; 🇳🇿 Auckland, New Zealand

Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis; 🇺🇸 Owosso, Michigan, United States

CEDOES - Diagnóstico e Pesquisa; 🇧🇷 Vitoria, ES, Brazil

Ospedale Civile di Montichiari; Centro Sclerosi Multipla; 🇮🇹 Montichiari, Lombardia, Italy

Hospital Universitario Puerta de Hierro Majadahonda; 🇪🇸 Majadahonda, Madrid, Spain

Care Clinic; 🇵🇱 Katowice, Poland

Hospital Universitario Reina Sofia; Servicio de Neurologia; 🇪🇸 Cordoba, Spain

Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia; 🇪🇸 Santa Cruz De Tenerife, Tenerife, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali; 🇹🇷 Istanbul, Turkey

Katip Celebi University Ataturk Training and Research Hospital; Neurology; 🇹🇷 Izmir, Turkey

Kocaeli University Hospital; Department of Neurology; 🇹🇷 Kocaeli, Turkey

University of South Florida; 🇺🇸 Tampa, Florida, United States