Back to resultsA Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Participants With Multiple Sclerosis
Primary Purpose
Multiple Sclerosis (MS)
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ocrelizumab
Ocrelizumab
rHuPH20
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis (MS)
Eligibility Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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
Sites / Locations
- University of Colorado; Anschutz Medical Campus Department of Neurology
- Georgetown University Medical Center
- University of South Florida School of Medicine Morsani Center for Advanced Health Care
- The NeuroMedical Clinic of Central Louisiana
- Ochsner Clinic Foundation
- John Hopkins University School of Medicine
- University of Massachusetts Medical School
- Wayne State University; Department of Neurology
- Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
- Washington Univ School of Med; Dept Neurology
- Columbia University Medical Center
- Cleveland Clinic Mellen Center; U10
- UC Health Neurology
- University of Pennsylvania
- University of Pittsburgh
- Premier Neurology
- Neurology Clinic PC
- University of Texas at Houston; Neurology
- Swedish Neuroscience Institute; Multiple Sclerosis Center
- MultiCare Health System Institute for Research and Innovation
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Group A: Cohorts A1-A4
Group A: Cohort A5
Group A: Cohort AA
Group B: Cohorts B1-B4
Arm Description
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
In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.
Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion
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
Outcomes
Primary Outcome Measures
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration
Percentage of participants with adverse events
Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters
Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS
Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA)
Secondary Outcome Measures
Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab
Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03972306
Brief Title
A Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Participants With Multiple Sclerosis
Official Title
A Phase Ib, Open-Label, Multicenter Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Patients With Multiple Sclerosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 12, 2019 (Actual)
Primary Completion Date
January 27, 2023 (Actual)
Study Completion Date
June 20, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with multiple sclerosis (MS).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis (MS)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
134 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A: Cohorts A1-A4
Arm Type
Experimental
Arm Description
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
Arm Title
Group A: Cohort A5
Arm Type
Experimental
Arm Description
In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.
Arm Title
Group A: Cohort AA
Arm Type
Experimental
Arm Description
Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion
Arm Title
Group B: Cohorts B1-B4
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Ocrelizumab
Intervention Description
Administered by subcutaneous Injection
Intervention Type
Drug
Intervention Name(s)
Ocrelizumab
Intervention Description
Administered by Intravenous (IV) Injection
Intervention Type
Drug
Intervention Name(s)
rHuPH20
Intervention Description
Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab
Primary Outcome Measure Information:
Title
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration
Time Frame
At predefined intervals from baseline through end of study (approximately 5 years)
Title
Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration
Time Frame
At predefined intervals from baseline through end of study (approximately 5 years)
Title
Percentage of participants with adverse events
Time Frame
Baseline to end of study (approximately 5 years)
Title
Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters
Time Frame
Baseline to end of study (approximately 5 years)
Title
Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS
Time Frame
Baseline to end of study (approximately 5 years)
Title
Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA)
Time Frame
Baseline to end of study (approximately 5 years)
Secondary Outcome Measure Information:
Title
Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab
Time Frame
Baseline to end of study (approximately 5 years)
Title
Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20
Time Frame
Baseline to end of study (approximately 5 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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).
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
University of Colorado; Anschutz Medical Campus Department of Neurology
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of South Florida School of Medicine Morsani Center for Advanced Health Care
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The NeuroMedical Clinic of Central Louisiana
City
Alexandria
State/Province
Louisiana
ZIP/Postal Code
71301
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
John Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Wayne State University; Department of Neurology
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
City
Owosso
State/Province
Michigan
ZIP/Postal Code
48867
Country
United States
Facility Name
Washington Univ School of Med; Dept Neurology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Cleveland Clinic Mellen Center; U10
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
UC Health Neurology
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Premier Neurology
City
Greer
State/Province
South Carolina
ZIP/Postal Code
29650
Country
United States
Facility Name
Neurology Clinic PC
City
Cordova
State/Province
Tennessee
ZIP/Postal Code
38018
Country
United States
Facility Name
University of Texas at Houston; Neurology
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Swedish Neuroscience Institute; Multiple Sclerosis Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
MultiCare Health System Institute for Research and Innovation
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
Learn more about this trial
A Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Participants With Multiple Sclerosis
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