Ocarina II: 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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05232825

Collaborator

(none)

232

Enrollment

Locations

Arms

33.7

Anticipated Duration (Months)

6.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Relapsing Multiple Sclerosis Primary Progressive Multiple Sclerosis	Drug: Ocrelizumab IV Drug: Ocrelizumab SC Drug: Methylprednisolone IV Drug: Diphenhydramine IV Drug: Dexamethasone given orally Drug: Desloratadine given orally	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

232 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 2, 2022

Anticipated Primary Completion Date :

Sep 10, 2023

Anticipated Study Completion Date :

Feb 22, 2025

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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 48 weeks of study treatment.	Drug: Ocrelizumab IV IV Injection Other Names: RO4964913 Drug: Methylprednisolone IV Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion Drug: Diphenhydramine IV Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab infusion
Experimental: 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 48 weeks of study treatment.	Drug: Ocrelizumab SC SC Injection Other Names: RO4964913 Drug: Dexamethasone given orally Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection Drug: Desloratadine given orally Participants will receive mandatory (corticosteroids and antihistamine) and optional (analgesic) prophylactic treatment before the start of each ocrelizumab injection

Arm

Intervention/Treatment

Active Comparator: 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 48 weeks of study treatment.

Drug: Ocrelizumab IV

IV Injection

Other Names:

RO4964913

Drug: Methylprednisolone IV

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

Drug: Diphenhydramine IV

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

Experimental: 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 48 weeks of study treatment.

Drug: Ocrelizumab SC

SC Injection

Other Names:

RO4964913

Drug: Dexamethasone given orally

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

Drug: Desloratadine given orally

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

Outcome Measures

Primary Outcome Measures

Serum ocrelizumab area under the concentration-time curve (AUCW1-12) [Day 1 to Week 12]

Secondary Outcome Measures

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]
Incidence of treatment-emergent antibodies to rHuPH20 [Day 1 to Week 48]
Proportion of participants achieving CD19+ B cell level <5 cells/uL [Weeks 12 and 24]
Levels of neurofilament light (NfL) biomarker in serum [Day 1, Weeks 12, 24, 48]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurology Associates PA	Maitland	Florida	United States	32751
2	University of South Florida	Tampa	Florida	United States	33612
3	The NeuroMedical Clinic of Central Louisiana	Alexandria	Louisiana	United States	71301
4	Johns Hopkins Hospital; Neurology	Baltimore	Maryland	United States	21205
5	Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis	Owosso	Michigan	United States	48867
6	UC Health Neurology	Dayton	Ohio	United States	45417
7	Premier Neurology	Greer	South Carolina	United States	29650
8	Neurology Clinic PC	Cordova	Tennessee	United States	38018
9	Memorial University of Newfoundland (MUN) - Faculty of Medicine - St. Clare's Mercy Hospital (SCM)	St. John's	Newfoundland and Labrador	Canada	A1B 3V6
10	Fakultni nemocnice u sv. Anny; Neurologicka klinika	Brno		Czechia	656 91
11	Charles University, Medical faculty, Hradec Kralove ;Department of Neurology	Hradec Králové		Czechia	500 05
12	Nemocnice Jihlava; NEU-Neurologicke oddeleni	Jihlava		Czechia	58633
13	Fakultni nemocnice Ostrava; MS centrum	Ostrava-Poruba		Czechia	708 52
14	Pardubicka Krajska Nemocnice; Department of Neurology	Pardubice		Czechia	532 03
15	Fakultni poliklinika VFN; RS centrum	Praha 2		Czechia	128 08
16	Institut neuropsychiatricke pece (INEP)	Praha 8		Czechia	186 00
17	Fakultni nemocnice Motol; Neurologicka klinika	Praha		Czechia	150 06
18	Krajska zdravotni a.s Nemocnice Teplice o.z.; RS centrum	Teplice		Czechia	415 01
19	A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche	Napoli	Campania	Italy	80131
20	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio	Italy	00133
21	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio	Italy	00189
22	Irccs A.O.U.San Martino Ist; Dinogmi	Genova	Liguria	Italy	16132
23	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia	Italy	20132
24	Ospedale Civile di Montichiari; Centro Sclerosi Multipla	Montichiari	Lombardia	Italy	25018
25	IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla	Pozzilli	Molise	Italy	86077
26	Optimal Clinical Trials	Auckland		New Zealand	1010
27	Hawkes Bay Hospital	Hastings		New Zealand	4120
28	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz		Poland	85-796
29	Care Clinic	Katowice		Poland	40-568
30	Centrum Neurologii Krzysztof Selmaj	Lodz		Poland	90-324
31	EMC Instytut Medyczny S.A.	Wrocław		Poland	50-220
32	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid	Spain	28222
33	Hospital Universitario Virgen Macarena	Seville	Sevilla	Spain	41071
34	Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia	Santa Cruz De Tenerife	Tenerife	Spain	38010
35	Hospital Regional Universitario de Malaga - Hospital General; Servicio de Neurologia	Malaga		Spain	29010