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

Relapsing Multiple Sclerosis Clinical Trial

— Ocarina II  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05232825
• Other study ID #: CN42097
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 3, 2022
• Est. completion date: April 1, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 multiple sclerosis (PPMS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 236
• Est. completion date: April 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Primary Progressive Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ocrelizumab IV
IV Injection
• Ocrelizumab SC
SC Injection
• Methylprednisolone IV
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
• Diphenhydramine IV
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
• Dexamethasone given orally
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection
• Desloratadine given orally
Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection

Locations

Country	Name	City	State
Brazil	Clinica Amo - Assistencia Medica Em Oncologia	Salvador	BA
Brazil	CEDOES - Diagnóstico e Pesquisa	Vitoria	ES
Czechia	Fakultni nemocnice u sv. Anny; Neurologicka klinika	Brno
Czechia	Charles University, Medical faculty, Hradec Kralove ;Department of Neurology	Hradec Králové
Czechia	Nemocnice Jihlava; NEU-Neurologicke oddeleni	Jihlava
Czechia	Fakultni nemocnice Ostrava; MS centrum	Ostrava-Poruba
Czechia	Pardubicka Krajska Nemocnice; Department of Neurology	Pardubice
Czechia	Fakultni nemocnice Motol; Neurologicka klinika	Praha
Czechia	Fakultni poliklinika VFN; RS centrum	Praha 2
Czechia	Krajska zdravotni a.s Nemocnice Teplice o.z.; RS centrum	Teplice
Italy	Ospedale Civile di Montichiari; Centro Sclerosi Multipla	Montichiari	Lombardia
Italy	IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla	Pozzilli	Molise
Italy	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio
Italy	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio
New Zealand	Optimal Clinical Trials	Auckland
New Zealand	Hawkes Bay Hospital	Hastings
Poland	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz
Poland	Care Clinic	Katowice
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Przychodnia EuroMediCare	Wroc?aw
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Neurologia	Cordoba
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia	Santa Cruz De Tenerife	Tenerife
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Turkey	Bakirkoy State Mental Hospital	Istanbul
Turkey	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	Namik Kemal Universitesi Sagli Uygulama ve Arastirma Hastanesi; Noroloji	Süleymanpa?a
United States	Johns Hopkins Hospital; Neurology	Baltimore	Maryland
United States	Neurology Clinic PC	Cordova	Tennessee
United States	UC Health Neurology	Dayton	Ohio
United States	Premier Neurology	Greenville	South Carolina
United States	Neurology Associates PA	Hickory	North Carolina
United States	Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis	Owosso	Michigan
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Brazil,  Czechia,  Italy,  New Zealand,  Poland,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum ocrelizumab area under the concentration-time curve (AUCW1-12)		Day 1 to Week 12
Secondary	Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS		Day 1 to Week 12
Secondary	Total number of T1Gd+ lesions as detected by brain MRI		Weeks 8 and 24
Secondary	Total number of new or enlarging T2 lesions as detected by brain MRI		Weeks 12 and 24
Secondary	Percentage of participants with Adverse Events		Day 1 to Week 48
Secondary	Incidence of treatment-emergent antidrug antibodies to ocrelizumab after SC or IV administration		Day 1 to Week 48
Secondary	Incidence of treatment-emergent antibodies to rHuPH20		Day 1 to Week 48
Secondary	Proportion of participants achieving CD19+ B cell level =5 cells/uL		Day 1 to Week 48