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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 22
- 主要终点
- Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
干预措施: 23-PPV (Biological)
Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
干预措施: 13-PCV Booster (Biological)
Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
干预措施: Influenza Vaccine (Biological)
Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
干预措施: KLH (Biological)
Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
干预措施: OCR (Drug)
Group A: OCR + Vaccines
Participants will receive dual infusion of OCR 300 milligrams (mg) on Day 1 and then on Day 15, and then participants will further receive immunization course (TT-containing adsorbed vaccine, 23-PPV either unboosted or boosted with 13-PCV, influenza vaccine, and repeated administration with KLH) at 12 weeks post-OCR treatment until Week 24. Participants who complete the 24-week immunization study period will have the option for retreatment with a single infusion of 600 mg OCR on Day 169 and subsequent single infusions (600 mg OCR) at intervals of 24 weeks. Participants who have received one or more infusions of OCR will enter the 48-week safety follow-up period.
干预措施: TT Vaccine (Biological)
Group B: Vaccines (Optional OCR in Extension)
Participants will receive immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization period.
干预措施: 23-PPV (Biological)
Group B: Vaccines (Optional OCR in Extension)
Participants will receive immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization period.
干预措施: Influenza Vaccine (Biological)
Group B: Vaccines (Optional OCR in Extension)
Participants will receive immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization period.
干预措施: KLH (Biological)
Group B: Vaccines (Optional OCR in Extension)
Participants will receive immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization period.
干预措施: OCR (Drug)
Group B: Vaccines (Optional OCR in Extension)
Participants will receive immunizations (TT-containing adsorbed vaccine, 23-PPV, influenza vaccine, and repeated administration with KLH) on Day 1 until Week 12 of the immunization period.
干预措施: TT Vaccine (Biological)
结局指标
主要结局
Percentage of Participants With Positive Response to TT Vaccine Measured 8 Weeks After TT Vaccine
时间窗: 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.
次要结局
- Percentage of Participants With Tetanus Antibody Titer >/=0.2 IU/mL or 2-Fold Increase in Tetanus Antibody Titers(4 weeks after TT vaccine)
- Mean Levels of Anti-Tetanus Antibody(Immediately prior to and at 4 and 8 weeks after TT vaccine)
- Mean Levels of Anti-Pneumococcal Antibody(Immediately prior to and 4 weeks after 23-PPV)
- Percentage of Participants With Positive Response Against Individual Pneumococcal Serotypes in 13-PCV(8 weeks after 23-PPV, which was 4 weeks after Group A1 participants received 13-PCV)
- Percentage of Participants With Positive Response to TT Vaccine Measured 4 Weeks After TT Vaccine(4 weeks after TT vaccine)
- Mean Levels of Anti-KLH Antibody: Ig M(Immediately prior to first KLH administration and 4, 8, and 12 weeks after first KLH administration)
- Percentage of Participants With 2-Fold Increase in Strain-Specific HI Titers(4 weeks after seasonal influenza vaccine administration)
- Percentage of Participants With 4-Fold Increase in Strain-Specific HI Titers(4 weeks after seasonal influenza vaccine administration)
- Mean Levels of Anti-KLH Antibody: Immunoglobulin (Ig) G(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(4 weeks after 23-PPV)
- Mean Level of Anti-Pneumococcal Antibody(Immediately prior to 23-PPV and 4 and 8 weeks after 23-PPV)
- Percentage of Participants With Seroprotection(4 weeks after seasonal influenza vaccine administration)
- Percentage of Participants With Positive Response Against >/=2 Pneumococcal Serotypes(4 weeks after 23-PPV)
- Percentage of Participants With Positive Response Against >/=12 Pneumococcal Serotypes(4 weeks after 23-PPV)
- Percentage of Participants With Seroconversion(4 weeks after influenza immunization)
- Strain-Specific Geometric Mean Titer Levels(Baseline and Week 4)
- Ratio of Strain-Specific Geometric Mean Titer Levels Postvaccination to Prevaccination(Immediately prior to and 4 weeks after influenza vaccine)
- Magnetic Resonance Imaging (MRI) Parameters: Volume of T2 Lesions(Baseline)
- MRI Parameters: Number of T2 Lesions(Baseline)
- MRI Parameters: Categorical Number of T2 Lesions(Baseline)
- MRI Parameters: Number of Gadolinium (Gd)-Enhancing T1 Lesions(Baseline)
- MRI Parameters: Categorical Number of Gd-enhancing T1 Lesions(Baseline)
- MRI Parameters: Normalized Brain Volume(Baseline)
- MRI Parameters: Volume of T2 Lesions: White Matter Volume(Baseline)
- MRI Parameters: Cortical Grey Matter Volume(Baseline)
- MRI Parameters: T1 Unenhancing Lesion Volume(Baseline)
- MRI Parameters: Total Number of Lesions(Baseline)
- Cellular Immune Response Assessed by Flow Cytometry(Days 1, 15, 85, 112, 140 and 169)
- Total Immunoglobulin(Days 1, 85, and 169)
- Percentage of Participants With Anti-Drug Antibody Formation(Up to 24 Weeks (ISP))
- Percentage of Participants With Adverse Events (AEs), Serious AEs, or AEs Leading to Study Discontinuation(During ISP (24 weeks for Group A and 12 weeks for Group B))