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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
102
The 23-PPV vaccine will be given as a 0.5-milliliter (mL) intramuscular (IM) injection in the deltoid muscle on Day 112 (Group A) or Day 28 (Group B).
The 13-PCV booster will be given as an IM injection in the deltoid muscle on Day 140 (select participants in Group A).
The influenza vaccine will be given as an IM injection in the deltoid muscle at any time between Day 85 and Day 144 (select participants in Group A) or any time between Day 1 and Day 85 (Group B).
North Central Neurology Associates
Cullman, Alabama, United States
Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine
For participants with pre-vaccination tetanus antibody titers \< 0.1 IU/mL, a positive response was defined as an antibody titer \>/= 0.2 IU/mL measured 8 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers \>/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 8 weeks after vaccination compared with pre-vaccination levels.
Time frame: 8 weeks after TT vaccine
Percentage of Participants With Positive Response to TT Vaccine Measured 4 Weeks After TT Vaccine
For participants with pre-vaccination tetanus antibody titers \< 0.1 IU/mL, a positive response was defined as an antibody titer \>/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers \>/= 0.1 IU/mL, a positive response was defined as at least a 4-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.
Time frame: 4 weeks after TT vaccine
Percentage of Participants With Tetanus Antibody Titer >/=0.2 IU/mL or 2-Fold Increase in Tetanus Antibody Titers
For participants with pre-vaccination tetanus antibody titers \< 0.1 IU/mL, a positive response was defined as an antibody titer \>/= 0.2 IU/mL measured 4 weeks after vaccination. For participants with pre-vaccination tetanus antibody titers \>/= 0.1 IU/mL, a positive response was defined as at least a 2-fold increase in antibody titers measured 4 weeks after vaccination compared with pre-vaccination levels.
Time frame: 4 weeks after TT vaccine
Mean Levels of Anti-Tetanus Antibody
Anti-tetanus antibody levels were assessed by enzyme-linked immunosorbent assay (ELISA).
Time frame: Immediately prior to and at 4 and 8 weeks after TT vaccine
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KLH will be given as a 1-mg subcutaneous (SC) injection on Days 84, 112, and 140 (Group A) or Days 1, 28, and 56 (Group B).
OCR will be given as an intravenous (IV) infusion at a dose of 600 mg, with the first dose given as two infusions of 300mg 14 days apart, according to the specifications described in the corresponding Group A and Group B arms.
The TT-containing adsorbed vaccine will be given as a 0.5-mL IM injection in the deltoid muscle on Day 85 (Group A) or Day 1 (Group B).
Territory Neurology and Research Institute
Tucson, Arizona, United States
Fullerton Neurology and Headache Center
Fullerton, California, United States
Scripps Clinic
La Jolla, California, United States
University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center
Miami, Florida, United States
University of South Florida
Tampa, Florida, United States
Michigan Institute for Neurological Disorders
Farmington Hills, Michigan, United States
The Minneapolis Clinic of Neurology
Golden Valley, Minnesota, United States
Mercy Hospital St. Louis / Mercy Clinic Neurology
Chesterfield, Missouri, United States
Cleveland Clinic Lou Ruvo; Center for Brain Research
Las Vegas, Nevada, United States
...and 12 more locations
Mean Levels of Anti-KLH Antibody: Immunoglobulin (Ig) G
Anti-KLH antibody levels were assessed by ELISA.
Time frame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
Mean Levels of Anti-KLH Antibody: Ig M
Anti-KLH antibody levels were assessed by ELISA.
Time frame: Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration
Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 23-PPV
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or greater than (\>) 1 microgram per milliliter (mcg/mL) rise compared with pre-vaccination levels.
Time frame: 4 weeks after 23-PPV
Percentage of Participants With Positive Response Against >/=2 Pneumococcal Serotypes
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or \> 1 mcg/mL rise compared with pre-vaccination levels.
Time frame: 4 weeks after 23-PPV
Percentage of Participants With Positive Response Against >/=12 Pneumococcal Serotypes
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or \> 1 mcg/mL rise compared with pre-vaccination levels.
Time frame: 4 weeks after 23-PPV
Mean Levels of Anti-Pneumococcal Antibody
Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).
Time frame: Immediately prior to and 4 weeks after 23-PPV
Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 13-PCV
Positive response against a serotype was defined as a 2-fold increase in anti-pneumococcal antibody level or \> 1 mcg/mL rise compared with pre-vaccination levels.
Time frame: 8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV
Mean Level of Anti-Pneumococcal Antibody
Serotype-specific antibody levels (IgG) were assessed by bead-based multi-analyte immunodetection (MAID).
Time frame: Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV
Percentage of Participants With Seroprotection
Seroprotection was defined as specific hemagglutination inhibition (HI) titers \>40 at 4 weeks after vaccination.
Time frame: 4 weeks after seasonal influenza vaccine administration
Percentage of Participants With 2-Fold Increase in Strain-Specific HI Titers
2-fold increase from prevaccination HI titer.
Time frame: 4 weeks after seasonal influenza vaccine administration
Percentage of Participants With 4-Fold Increase in Strain-Specific HI Titers
4-fold increase from prevaccination HI titer.
Time frame: 4 weeks after seasonal influenza vaccine administration
Percentage of Participants With Seroconversion
Seroconversion at 4 weeks after vaccination defined, as per protocol, as a prevaccination HI titer \<10 and an HI titer \>40 at 4 weeks after vaccination. Seroconversion at 4 weeks after vaccination, defined per FDA guidance, as either a) a pre-vaccination HI titer \<10 and HI titer \>/= 40 at 4 weeks after vaccination, or b) a pre-vaccination HI titer \>/= 10 and at least 4-fold increase in HI antibody titer at 4 weeks after vaccination.
Time frame: 4 weeks after influenza immunization
Strain-Specific Geometric Mean Titer Levels
Geometric mean titers (GMTs) in participants in Groups A2 and B were measured 4 weeks after vaccination.
Time frame: Baseline and Week 4
Ratio of Strain-Specific Geometric Mean Titer Levels Postvaccination to Prevaccination
Strain-specific GMT ratios were calculated as post-vaccination : pre-vaccination.
Time frame: Immediately prior to and 4 weeks after influenza vaccine
Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Number of T2 Lesions
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Categorical Number of T2 Lesions
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Number of Gadolinium (Gd)-Enhancing T1 Lesions
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Categorical Number of Gd-enhancing T1 Lesions
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Normalized Brain Volume
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Volume of T2 Lesions: White Matter Volume
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Cortical Grey Matter Volume
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: T1 Unenhancing Lesion Volume
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
MRI Parameters: Total Number of Lesions
MRI assessments done to evaluate the long-term effects of ocrelizumab on MRI parameters.
Time frame: Baseline
Cellular Immune Response Assessed by Flow Cytometry
Flow cytometry is a laser-based technology commonly used for cell counting and sorting. In this study, this outcome measure is focusing on a single variable, CD19 count (total B cells). LLN = 80 cells/ul. Repleted is defined as CD19 \>= LLN or baseline, whichever is lower.
Time frame: Days 1, 15, 85, 112, 140 and 169
Total Immunoglobulin
Time frame: Days 1, 85, and 169
Percentage of Participants With Anti-Drug Antibody Formation
Anti-Drug Antibodies (ADA) may induce unwanted side effects, especially in biotechnology-derived pharmaceuticals, such as therapeutic antibodies and growth factors.
Time frame: Up to 24 Weeks (ISP)
Percentage of Participants With Adverse Events (AEs), Serious AEs, or AEs Leading to Study Discontinuation
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious AE is any AE that is fatal, life-threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug, or is a significant medical event in the investigator's judgment.
Time frame: During ISP (24 weeks for Group A and 12 weeks for Group B)