Print

Purpose

This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with multiple sclerosis (MS).

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Active, not recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.