A Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Participants With Multiple Sclerosis
- Conditions
- Multiple Sclerosis (MS)
- Interventions
- Registration Number
- NCT03972306
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with multiple sclerosis (MS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 134
- Diagnosis of Primary Progressive Multiple Sclerosis (PPMS) or Relapsing Multiple Sclerosis (RMS) according to the revised McDonald 2017 criteria (Thompson et al. 2018)
- Expanded Disability Status Scale (EDSS) score, 0-6.5, inclusive, at screening
- Absence of relapses for 30 days prior to the screening visit
- For the dose escalation phase for participants pretreated with ocrelizumab (Group A):
treatment with IV ocrelizumab for at least 1 year prior to screening (i.e., at least two 600-mg doses of ocrelizumab separated by 24 weeks)
- For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for 6 months after the final dose of ocrelizumab.
- For female perticipants without reproductive potential:
Women may be enrolled if post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile (i.e., hysterectomy, complete bilateral oophorectomy).
- MS disease duration of more than 15 years for participants with an Expanded Disability Status Scale (EDSS) score <2.0 at screening.
- Known presence of other neurologic disorders that may mimic MS, including, but not limited to, the following:
- History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord
- History or known presence of Central Nervous System (CNS) or spinal cord tumor (e.g., meningioma,glioma)
- History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency)
- History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1, herpes zoster and myelopathy.
- History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke syndrome)
- Neuromyelitis optica
- History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjögren syndrome, Behçet disease, sarcoidosis).
- History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B: Cohorts B1-B4 Ocrelizumab Ocrelizumab treatment- naive participants will receive a minimum of 3 patients in Cohort B will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. * Cohort B1: 40 mg of SC ocrelizumab * Cohort B2: 200 mg of SC ocrelizumab * Cohort B3: 600 mg of SC ocrelizumab * Cohort B4: 1200 mg of SC ocrelizumab Group B: Cohorts B1-B4 rHuPH20 Ocrelizumab treatment- naive participants will receive a minimum of 3 patients in Cohort B will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. * Cohort B1: 40 mg of SC ocrelizumab * Cohort B2: 200 mg of SC ocrelizumab * Cohort B3: 600 mg of SC ocrelizumab * Cohort B4: 1200 mg of SC ocrelizumab Group A: Cohort A5 rHuPH20 In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. Group A: Cohorts A1-A4 rHuPH20 Participants (participants pretreated with ocrelizumab) will receive a single injection of subcutaneous (SC) ocrelizumab co-mixed with rHuPH20 in the abdomen. For every new dose level, recruitment will be staggered by enrolling 1 participant in each cohort followed by a 48-hour waiting period to review safety and tolerability data by the Safety Monitoring Committee (SMC) prior to enrolling subsequent participants in the same cohort. Currently, the planned dose escalation steps for patients who enroll in Group A are as follows: * Cohort A1: 40 mg of SC ocrelizumab * Cohort A2: 200 mg of SC ocrelizumab * Cohort A3: 600 mg of SC ocrelizumab * Cohort A4: 1200 mg of SC ocrelizumab Group A: Cohorts A1-A4 Ocrelizumab Participants (participants pretreated with ocrelizumab) will receive a single injection of subcutaneous (SC) ocrelizumab co-mixed with rHuPH20 in the abdomen. For every new dose level, recruitment will be staggered by enrolling 1 participant in each cohort followed by a 48-hour waiting period to review safety and tolerability data by the Safety Monitoring Committee (SMC) prior to enrolling subsequent participants in the same cohort. Currently, the planned dose escalation steps for patients who enroll in Group A are as follows: * Cohort A1: 40 mg of SC ocrelizumab * Cohort A2: 200 mg of SC ocrelizumab * Cohort A3: 600 mg of SC ocrelizumab * Cohort A4: 1200 mg of SC ocrelizumab Group A: Cohort A5 Ocrelizumab In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen. Group A: Cohort AA Ocrelizumab Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion
- Primary Outcome Measures
Name Time Method Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration At predefined intervals from baseline through end of study (approximately 5 years) Percentage of participants with adverse events Baseline to end of study (approximately 5 years) Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters Baseline to end of study (approximately 5 years) Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration At predefined intervals from baseline through end of study (approximately 5 years) Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA) Baseline to end of study (approximately 5 years) Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS Baseline to end of study (approximately 5 years)
- Secondary Outcome Measures
Name Time Method Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20 Baseline to end of study (approximately 5 years) Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab Baseline to end of study (approximately 5 years)
Trial Locations
- Locations (20)
University of Colorado
🇺🇸Aurora, Colorado, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of South Florida School of Medicine Morsani Center for Advanced Health Care
🇺🇸Tampa, Florida, United States
The NeuroMedical Clinic of Central Louisiana
🇺🇸Alexandria, Louisiana, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
John Hopkins University School of Medicine
🇺🇸Baltimore, Maryland, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
🇺🇸Owosso, Michigan, United States
Washington Univ School of Med
🇺🇸Saint Louis, Missouri, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Cleveland Clinic Mellen Center
🇺🇸Cleveland, Ohio, United States
UC Health Neurology
🇺🇸Dayton, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Premier Neurology
🇺🇸Greer, South Carolina, United States
Neurology Clinic PC
🇺🇸Cordova, Tennessee, United States
University of Texas at Houston
🇺🇸Houston, Texas, United States
Swedish Neuroscience Institute
🇺🇸Seattle, Washington, United States
MultiCare Health System Institute for Research and Innovation
🇺🇸Tacoma, Washington, United States