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

Multiple Sclerosis (MS) Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03972306
• Other study ID #: CN41144
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: August 12, 2019
• Est. completion date: June 20, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 134
• Est. completion date: June 20, 2025
• Est. primary completion date: June 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis (MS)
• Sclerosis

Intervention

Drug:
• Ocrelizumab
Administered by subcutaneous Injection
• Ocrelizumab
Administered by Intravenous (IV) Injection
• rHuPH20
Administered in a 2-mL glass vial as a sterile, single-use, injectable liquid to be manually mixed with SC ocrelizumab

Locations

Country	Name	City	State
United States	The NeuroMedical Clinic of Central Louisiana	Alexandria	Louisiana
United States	University of Colorado; Anschutz Medical Campus Department of Neurology	Aurora	Colorado
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	Cleveland Clinic Mellen Center; U10	Cleveland	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	UC Health Neurology	Dayton	Ohio
United States	Wayne State University; Department of Neurology	Detroit	Michigan
United States	Premier Neurology	Greenville	South Carolina
United States	University of Texas at Houston; Neurology	Houston	Texas
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis	Owosso	Michigan
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington Univ School of Med; Dept Neurology	Saint Louis	Missouri
United States	Swedish Neuroscience Institute; Multiple Sclerosis Center	Seattle	Washington
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
United States	University of South Florida School of Medicine Morsani Center for Advanced Health Care	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Percentage of participants with adverse events		Baseline to end of study (approximately 5 years)
Primary	Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters		Baseline to end of study (approximately 5 years)
Primary	Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS		Baseline to end of study (approximately 5 years)
Primary	Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA)		Baseline to end of study (approximately 5 years)
Secondary	Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab		Baseline to end of study (approximately 5 years)
Secondary	Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20		Baseline to end of study (approximately 5 years)