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A Study To Investigate The Pharmacokinetics, Safety, And Tolerability Of Subcutaneous Ocrelizumab Administration In Participants With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT03972306
Recruitment Status : Recruiting
First Posted : June 3, 2019
Last Update Posted : February 10, 2021
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Multiple Sclerosis (MS) Drug: Ocrelizumab Drug: rHuPH20 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 12, 2019
Estimated Primary Completion Date : February 15, 2021
Estimated Study Completion Date : October 2, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Ocrelizumab

Arm Intervention/treatment
Experimental: Group A: Cohorts A1-A4

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
Drug: Ocrelizumab
Administered by subcutaneous Injection

Drug: rHuPH20
Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab

Experimental: Group A: Cohort A5
In the non-randomized subphase, participants will receive a single SC injection of ocrelizumab co-mixed with rHuPH20 in the abdomen.
Drug: Ocrelizumab
Administered by subcutaneous Injection

Drug: rHuPH20
Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab

Experimental: Group A: Cohort AA
Participants will receive a single 600-mg dose ocrelizumab by intravenous (IV) infusion
Drug: Ocrelizumab
Administered by Intravenous (IV) Injection

Experimental: Group B: Cohorts B1-B4

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
Drug: Ocrelizumab
Administered by subcutaneous Injection

Drug: rHuPH20
Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab




Primary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. Percentage of participants with adverse events [ Time Frame: Baseline to end of study (approximately 5 years) ]
  4. Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters [ Time Frame: Baseline to end of study (approximately 5 years) ]
  5. Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS [ Time Frame: Baseline to end of study (approximately 5 years) ]
  6. 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 Measures :
  1. Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab [ Time Frame: Baseline to end of study (approximately 5 years) ]
  2. Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20 [ Time Frame: Baseline to end of study (approximately 5 years) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03972306


Contacts
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Contact: Reference Study ID Number: CN41144 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03972306    
Other Study ID Numbers: CN41144
First Posted: June 3, 2019    Key Record Dates
Last Update Posted: February 10, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Ocrelizumab
Immunologic Factors
Physiological Effects of Drugs