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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 : Active, not recruiting
First Posted : February 10, 2022
Last Update Posted : January 17, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 27, 2022
First Posted Date  ICMJE February 10, 2022
Last Update Posted Date January 17, 2023
Actual Study Start Date  ICMJE May 3, 2022
Estimated Primary Completion Date September 10, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsing Multiple Sclerosis
  • Primary Progressive Multiple Sclerosis
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 13, 2023)
234
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2022)
232
Estimated Study Completion Date  ICMJE February 22, 2025
Estimated Primary Completion Date September 10, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Canada,   Czechia,   Italy,   New Zealand,   Poland,   Spain,   Turkey,   United States
Removed Location Countries Russian Federation,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT05232825
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Current Responsible Party Hoffmann-La Roche
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Hoffmann-La Roche
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP