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)

• ClinicalTrials.gov Identifier: NCT05232825
• Recruitment Status: Active, not recruiting
• First Posted: February 10, 2022
• Last Update Posted: January 17, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 27, 2022
• First Posted Date: February 10, 2022
• Last Update Posted Date: January 17, 2023
• Actual Study Start Date: May 3, 2022
• Estimated Primary Completion Date: September 10, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 31, 2022): Serum ocrelizumab area under the concentration-time curve (AUCW1-12) [ Time Frame: Day 1 to Week 12 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 31, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Relapsing Multiple Sclerosis
• Primary Progressive Multiple Sclerosis

Intervention

• Drug: Ocrelizumab IV
  IV Injection
  Other Name: RO4964913
• Drug: Ocrelizumab SC
  SC 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
• 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

Study Arms

• 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.
  Interventions:

  • Drug: Ocrelizumab IV
  • Drug: Methylprednisolone IV
  • Drug: Diphenhydramine IV
• 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.
  Interventions:

  • Drug: Ocrelizumab SC
  • Drug: Dexamethasone given orally
  • Drug: Desloratadine given orally

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 13, 2023): 234
• Original Estimated Enrollment (submitted: January 31, 2022): 232
• Estimated Study Completion Date: February 22, 2025
• Estimated Primary Completion Date: September 10, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Canada, Czechia, Italy, New Zealand, Poland, Spain, Turkey, United States
• Removed Location Countries: Russian Federation, Ukraine

Administrative Information

• NCT Number: NCT05232825
• Other Study ID Numbers: CN42097
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: January 2023