Clinical trial NCT03972306: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Sclerosis (MS)
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-06-03
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the pharmacokinetics, safety and tolerability, and immunogenicity of ocrelizumab administered subcutaneously to participants with 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

Primary outcomes:
measure: Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following subcutaneous (SC) administration
timeFrame: At predefined intervals from baseline through end of study (approximately 5 years)
measure: Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab following single IV (intravenous Infusion)administration
timeFrame: At predefined intervals from baseline through end of study (approximately 5 years)
measure: Percentage of participants with adverse events
timeFrame: Baseline to end of study (approximately 5 years)
measure: Percentage of participants with change from baseline in Marked Abnormality in Electrocardiogram (ECG) Parameters
timeFrame: Baseline to end of study (approximately 5 years)
measure: Incidence of local pain at site of injection assessed using Visual Analog Scale (VAS
timeFrame: Baseline to end of study (approximately 5 years)
measure: Incidence of local-injection reaction (ISR) assessed using Local Injection-Site Symptom Assessment (LISSA)
timeFrame: Baseline to end of study (approximately 5 years)
Secondary outcomes:
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs) to ocrelizumab
timeFrame: Baseline to end of study (approximately 5 years)
measure: Percentage of Participants with Anti-Drug Antibodies (ADAs) to rHuPH20
timeFrame: Baseline to end of study (approximately 5 years)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida School of Medicine Morsani Center for Advanced Health Care
state: Florida
city: Alexandria
country: United States
facility: The NeuroMedical Clinic of Central Louisiana
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Owosso
country: United States
facility: Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis
state: Michigan
city: Saint Louis
country: United States
facility: Washington Univ School of Med
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Mellen Center
state: Ohio
city: Dayton
country: United States
facility: UC Health Neurology
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Greer
country: United States
facility: Premier Neurology
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic PC
state: Tennessee
city: Houston
country: United States
facility: University of Texas at Houston
state: Texas
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: