A Study To Investigate The Pharmacokinetics, Pharmacodynamics, Safety And Radiological And Clinical Effects Of Subcutaneous Ocrelizumab Versus Intravenous Ocrelizumab In Patients With Multiple Sclerosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 236
- 试验地点
- 37
- 主要终点
- Serum Ocrelizumab Area Under the Concentration-Time Curve Over the First 12 Weeks (AUCW1-12) After SC Administration
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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 96 weeks of study treatment.
干预措施: Diphenhydramine IV (Drug)
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 96 weeks of study treatment.
干预措施: Desloratadine given orally (Drug)
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 96 weeks of study treatment.
干预措施: Dexamethasone given orally (Drug)
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 96 weeks of study treatment.
干预措施: Ocrelizumab IV (Drug)
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 96 weeks of study treatment.
干预措施: Ocrelizumab SC (Drug)
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 96 weeks of study treatment.
干预措施: Methylprednisolone IV (Drug)
结局指标
主要结局
Serum Ocrelizumab Area Under the Concentration-Time Curve Over the First 12 Weeks (AUCW1-12) After SC Administration
时间窗: Day 1 Week 1 to Week 12
次要结局
- Maximum Serum Concentration (Cmax) of Ocrelizumab SC(Day 1 Week 1 to Week 24)
- Rate of Gadolinium-enhancing Lesions on T1-weighted (T1Gd+) Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) at Weeks 8 and 24(At Weeks 8 and 24)
- Rate of New or Enlarging T2 Lesions as Detected by Brain MRI at Weeks 12 and 24(At Weeks 12 and 24)
- Number of Participants With Adverse Events (AEs)(From initiation of study drug until 24 weeks after the final dose of study drug (up to 138.1 weeks))
- Number of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab After SC or IV Administration(Up to 138.1 weeks)
- Number of Participants With ADAs to rHuPH20 After Ocrelizumab SC Administration(Up to 138.1 weeks)
- Percentage of Participants Who Achieved CD19+ B Cell Level of ≤5 Cells/Microliters (µL) at Weeks 12, 24, 48, and/or 96(At Weeks 12, 24, 48, and 96)