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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 (Ocarina II)

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ClinicalTrials.gov Identifier: NCT05232825
Recruitment Status : Recruiting
First Posted : February 10, 2022
Last Update Posted : November 21, 2022
Sponsor:
Information provided by (Responsible Party):
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).

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

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Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : September 10, 2023
Estimated Study Completion Date : February 22, 2025


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 Name: 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 Name: 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




Primary Outcome Measures :
  1. Serum ocrelizumab area under the concentration-time curve (AUCW1-12) [ Time Frame: Day 1 to Week 12 ]

Secondary Outcome Measures :
  1. Maximum serum concentration (Cmax) of ocrelizumab SC in patients with MS [ Time Frame: Day 1 to Week 12 ]
  2. Total number of T1Gd+ lesions as detected by brain MRI [ Time Frame: Weeks 8 and 24 ]
  3. Total number of new or enlarging T2 lesions as detected by brain MRI [ Time Frame: Weeks 12 and 24 ]
  4. Percentage of participants with Adverse Events [ Time Frame: Day 1 to Week 48 ]
  5. Incidence of treatment-emergent antidrug antibodies to ocrelizumab after SC or IV administration [ Time Frame: Day 1 to Week 48 ]
  6. Incidence of treatment-emergent antibodies to rHuPH20 [ Time Frame: Day 1 to Week 48 ]
  7. Proportion of participants achieving CD19+ B cell level <5 cells/uL [ Time Frame: Weeks 12 and 24 ]
  8. Levels of neurofilament light (NfL) biomarker in serum [ Time Frame: Day 1, Weeks 12, 24, 48 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05232825


Contacts
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Contact: Reference Study ID Number: CN42097 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05232825    
Other Study ID Numbers: CN42097
First Posted: February 10, 2022    Key Record Dates
Last Update Posted: November 21, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Diphenhydramine
Promethazine
Dexamethasone
Methylprednisolone
Desloratadine
Ocrelizumab
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Neuroprotective Agents
Protective Agents
Sleep Aids, Pharmaceutical