Clinical trial NCT02545868: A Study to Evaluate the Effects of Ocrelizumab on Immune Responses In Participants With Relapsing Forms of Multiple Sclerosis
Official title: A Phase IIIB, Multicenter, Randomized, Parallel-Group, Open-Label Study to Evaluate the Effects of Ocrelizumab on Immune Responses in Patients With Relapsing Forms of Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2015-09-10
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This multicenter, randomized, open-label study will evaluate the immune response to vaccines (tetanus toxoid \[TT\]-containing adsorbed vaccine, 23-valent pneumococcal polysaccharide vaccine \[23-PPV\] either unboosted or boosted with 13-valent pneumococcal conjugate vaccine \[13-PCV\], influenza vaccine, keyhole limpet hemocyanin \[KLH\]) after administration of a dose of ocrelizumab (OCR) in participants with relapsing multiple sclerosis (RMS).


Eligibility criteria: Inclusion Criteria:

* Diagnosis of RMS in accordance with the revised McDonald criteria
* Received at least one previous immunization against TT or tetanus and diphtheria (DT/Td) or tetanus, diphtheria, and acellular pertussis (DTaP/Tdap)
* Expanded Disability Status Scale (EDSS) at Screening from 0 to 5.5 points, inclusive
* For sexually active female participants of reproductive potential, use of reliable means of contraception

Exclusion Criteria:

* Contraindications for or intolerance to oral or IV corticosteroids, including IV methylprednisolone, according to the country label
* Known presence of other neurologic disorders
* Treatment with any investigational agent within 24 weeks of screening or 5 half-lives of the investigational drug, whichever is longer, or treatment with any experimental procedure for multiple sclerosis

Primary outcomes:
measure: Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine
timeFrame: 8 weeks after TT vaccine
Secondary outcomes:
measure: Percentage of Participants With Positive Response to TT Vaccine Measured 4 Weeks After TT Vaccine
timeFrame: 4 weeks after TT vaccine
measure: Percentage of Participants With Tetanus Antibody Titer >/=0.2 IU/mL or 2-Fold Increase in Tetanus Antibody Titers
timeFrame: 4 weeks after TT vaccine
measure: Mean Levels of Anti-Tetanus Antibody
timeFrame: Immediately prior to and at 4 and 8 weeks after TT vaccine
measure: Mean Levels of Anti-KLH Antibody: Immunoglobulin (Ig) G
timeFrame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
measure: Mean Levels of Anti-KLH Antibody: Ig M
timeFrame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
measure: Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 23-PPV
timeFrame: 4 weeks after 23-PPV
measure: Percentage of Participants With Positive Response Against >/=2 Pneumococcal Serotypes
timeFrame: 4 weeks after 23-PPV
measure: Percentage of Participants With Positive Response Against >/=12 Pneumococcal Serotypes
timeFrame: 4 weeks after 23-PPV
measure: Mean Levels of Anti-Pneumococcal Antibody
timeFrame: Immediately prior to and 4 weeks after 23-PPV
measure: Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 13-PCV
timeFrame: 8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV
measure: Mean Level of Anti-Pneumococcal Antibody
timeFrame: Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV
measure: Percentage of Participants With Seroprotection
timeFrame: 4 weeks after seasonal influenza vaccine administration
measure: Percentage of Participants With 2-Fold Increase in Strain-Specific HI Titers
timeFrame: 4 weeks after seasonal influenza vaccine administration
measure: Percentage of Participants With 4-Fold Increase in Strain-Specific HI Titers
timeFrame: 4 weeks after seasonal influenza vaccine administration
measure: Percentage of Participants With Seroconversion
timeFrame: 4 weeks after influenza immunization
measure: Strain-Specific Geometric Mean Titer Levels
timeFrame: Baseline and Week 4
measure: Ratio of Strain-Specific Geometric Mean Titer Levels Postvaccination to Prevaccination
timeFrame: Immediately prior to and 4 weeks after influenza vaccine
measure: Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions
timeFrame: Baseline
measure: MRI Parameters: Number of T2 Lesions
timeFrame: Baseline
measure: MRI Parameters: Categorical Number of T2 Lesions
timeFrame: Baseline
measure: MRI Parameters: Number of Gadolinium (Gd)-Enhancing T1 Lesions
timeFrame: Baseline
measure: MRI Parameters: Categorical Number of Gd-enhancing T1 Lesions
timeFrame: Baseline
measure: MRI Parameters: Normalized Brain Volume
timeFrame: Baseline
measure: MRI Parameters: Volume of T2 Lesions: White Matter Volume
timeFrame: Baseline
measure: MRI Parameters: Cortical Grey Matter Volume
timeFrame: Baseline
measure: MRI Parameters: T1 Unenhancing Lesion Volume
timeFrame: Baseline
measure: MRI Parameters: Total Number of Lesions
timeFrame: Baseline
measure: Cellular Immune Response Assessed by Flow Cytometry
timeFrame: Days 1, 15, 85, 112, 140 and 169
measure: Total Immunoglobulin
timeFrame: Days 1, 85, and 169
measure: Percentage of Participants With Anti-Drug Antibody Formation
timeFrame: Up to 24 Weeks (ISP)
measure: Percentage of Participants With Adverse Events (AEs), Serious AEs, or AEs Leading to Study Discontinuation
timeFrame: During ISP (24 weeks for Group A and 12 weeks for Group B)
Other outcomes:
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates
state: Alabama
city: Tucson
country: United States
facility: Territory Neurology and Research Institute
state: Arizona
city: Fullerton
country: United States
facility: Fullerton Neurology and Headache Center
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Miami
country: United States
facility: University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Farmington Hills
country: United States
facility: Michigan Institute for Neurological Disorders
state: Michigan
city: Golden Valley
country: United States
facility: The Minneapolis Clinic of Neurology
state: Minnesota
city: Chesterfield
country: United States
facility: Mercy Hospital St. Louis / Mercy Clinic Neurology
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo; Center for Brain Research
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Staten Island
country: United States
facility: Staten Island Univ Hospital
state: New York
city: Hickory
country: United States
facility: Neurology Associates PA
state: North Carolina
city: Columbus
country: United States
facility: Ohio Health Research Institute Grant Medical Center
state: Ohio
city: Westerville
country: United States
facility: MDH Research LLC
state: Ohio
city: Abington
country: United States
facility: Abington Neurological Associates
state: Pennsylvania
city: Cordova
country: United States
facility: Neurology Clinic PC
state: Tennessee
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain MS Clinic
state: Utah
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia Hospital; Division of Neurology
state: British Columbia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Bar-Or A, Calkwood JC, Chognot C, Evershed J, Fox EJ, Herman A, Manfrini M, McNamara J, Robertson DS, Stokmaier D, Wendt JK, Winthrop KL, Traboulsee A. Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Neurology. 2020 Oct 6;95(14):e1999-e2008. doi: 10.1212/WNL.0000000000010380. Epub 2020 Jul 29.