SAFETY AND IMMUNOGENICITY STUDY OF VLA15, A MULTIVALENT RECOMBINANT OSPA BASED VACCINE CANDIDATE AGAINST LYME BORRELIOSIS: A RANDOMIZED, CONTROLLED, OBSERVER-BLIND PHASE 2 STUDY IN A HEALTHY PEDIATRIC AND ADULT STUDY POPULATION
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 625
- 试验地点
- 41
- 主要终点
- Geometric Mean Titers (GMTs) for Immunoglobulin G (IgG) Against Each Outer Surface Protein A (OspA) Serotype (ST1 to ST6) at Day 208 During the Main Study Phase
研究概览
简要总结
VLA15-221 is a Phase 2 study, which will be conducted in two parts: Main Study Phase (Part A) and Booster Phase (Part B). The study will compare the safety and immunogenicity of two different primary immunization schedules applying three (Month 0-2-6) or two (Month 0- 6) vaccinations. Within the study, 600 healthy subjects aged 5-65 years will be included. Subjects with a history of Lyme borreliosis (previous infection with Borrelia) as well as Borrelia naïve subjects will be enrolled. Study duration per subject will be a maximum of 50 months per subject.
详细描述
VLA15-221 is a randomized, observer-blind, placebo controlled, multicenter Phase 2 study, which is set up in two parts: Main Study Phase (Part A) and Booster Phase (Part B). In Part A 600 subjects aged 5-65 years will be enrolled 1:1:1 into three groups: Group 1 will be vaccinated with VLA15 at Month 0-2-6, Group 2 will be vaccinated with VLA15 at Month 0-6 and with placebo at Month 2 and Group 3 will be vaccinated with placebo at Month 0-2-6. In Part B all eligible subjects will receive booster injections with VLA15 or placebo at Month 18, 30 and 42.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is aged 5 to 65 years at the day of screening (Visit 0)
- •Subject is of good general health
- •Parent(s)/legal representative(s) and subject understand the study and its procedures, agree to its provisions
- •for subjects aged 18-65 years: written informed consent prior to any study related procedures
- •for subjects aged 5-17 years: written informed consent by the subject's legal representative(s), according to local requirements, and written informed assent of the subject, if applicable, prior to any study related procedures.
- •If subject is of childbearing potential: Subject has a negative serum pregnancy test at screening (Visit 0) and agrees to employ adequate birth control measures according to following timelines:
- •Main Study Phase: duration of entire study
- •Booster Phase: until 5 months after each booster vaccination (Booster 1 until Month 23, Booster 2 until Month 35 and Booster 3 until Month 47)
- •Subject is willing and able to comply with scheduled visits, treatment plan, and other study procedures
- •Subject is available for the duration of the study and can be contacted by telephone during study participation
排除标准
- •Subject has a chronic illness related to Lyme borreliosis (LB), an active symptomatic LB, or received treatment for LB within the last 3 months prior to Day 1;
- •Subject received previous vaccination against LB;
- •Subject had a tick bite within 4 weeks prior to Day 1;
- •Subject has a medical history of or currently has a clinically relevant disease;
- •Subject has a medical history of or currently has a neuro- inflammatory or autoimmune disease;
- •Subject has a known thrombocytopenia, bleeding disorder, or received anticoagulants in the 3 weeks prior to Day 1;
- •Subject has received an active or passive immunization within 4 weeks prior to Day 1;
- •Subject has received any other registered or non-registered medicinal product in another clinical trial within 4 weeks prior to vaccination at Day 1;
- •Subject has a known or suspected defect of the immune system or received immuno-suppressive therapy within 4 weeks prior to Day 1;
- •Subject has a history of anaphylaxis of unknown cause or severe allergic reactions of unknown cause or has a known hypersensitivity or allergic reactions to one of the components of the vaccine;
- •Subject had any malignancy in the past 5 years;
- •Subject is pregnant, has plans to become pregnant during the course of the study or is lactating at the time of enrollment;
- •Subject has donated or plans to donate blood or blood-derived products 4 weeks prior to Day 1;
- •Subject has any condition that may compromise its well-being, might interfere with evaluation of study endpoints, or would limit the subject's ability to complete the study;
- •Subject is in a dependent relationship with the sponsor/investigator
研究组 & 干预措施
Part A+B - Group 1
Part A: VLA15 at Month 0, 2 and 6 Part B: VLA15 at Month 18, 30 and 42
干预措施: VLA15 (Biological)
Part A+B - Group 2
Part A: VLA15 at Month 0 and 6, placebo at Month 2 Part B: VLA15 at Month 18, 30 and 42
干预措施: VLA15 (Biological)
Part A+B - Group 2
Part A: VLA15 at Month 0 and 6, placebo at Month 2 Part B: VLA15 at Month 18, 30 and 42
干预措施: Placebo (Biological)
Part A+B - Group 3
Part A: Placebo at Month 0, 2 and 6 Part B: Placebo at Month 18, 30 and 42
干预措施: Placebo (Biological)
结局指标
主要结局
Geometric Mean Titers (GMTs) for Immunoglobulin G (IgG) Against Each Outer Surface Protein A (OspA) Serotype (ST1 to ST6) at Day 208 During the Main Study Phase
时间窗: Day 208 (Month 7)
GMTs for IgG against each OspA serotype ST1 to ST6, determined by an IgG binding assay at Day 208 is presented in this outcome measure.
Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Any Vaccination During the Main Study Phase
时间窗: From Day 1 to Day 7 after vaccination 1, 2 or 3 at Month 0, 2 and 6 respectively
Participants or their legal guardians were required to record any solicited local and systemic adverse events in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema (redness), swelling and induration (hardening). Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever. Two-sided 95% confidence intervals were calculated according to Altman method.
Percentage of Participants With Solicited Local and Solicited Systemic Adverse Events (AEs) Within 7 Days After Vaccination 1
时间窗: From Day 1 to Day 7 after vaccination 1 at Month 0
Participants or their legal guardians were required to record any solicited local and systemic AEs in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema/redness meeting grading scale (MGS), swelling MGS and induration/hardening MGS. Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever.
Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 2
时间窗: From Day 1 to Day 7 after vaccination 2 at Month 2
Participants or their legal guardians were required to record any solicited local and systemic AEs in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema/redness MGS, swelling MGS and induration/hardening MGS. Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever.
Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 3
时间窗: From Day 1 to Day 7 after vaccination 3 at Month 6
Participants or their legal guardians were required to record any solicited local and systemic AEs in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema/redness MGS, swelling MGS and induration/hardening MGS. Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever.
Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Any Vaccination During the Main Study Phase
时间窗: From Day 1 to Day 7 after any vaccination 1, 2 or 3 at Month 0, 2 and 6, respectively
Participants or their legal guardians were required to record any solicited local and systemic AEs in the electronic diary. Solicited symptoms were pre-defined symptoms which were collected via an electronic diary. Solicited local AEs included pain, tenderness, erythema/redness MGS, swelling MGS and induration/hardening MGS. Solicited systemic AEs included headache, muscle pain, joint pain, nausea, vomiting, fatigue and fever.
Geometric Mean Titers (GMTs) for Immunoglobulin G (IgG) Against Each Outer Surface Protein A (OspA) Serotype (ST1 to ST6) at Day 208 During the Main Study Phase
时间窗: At Day 208 (Month 7)
GMTs for IgG against each OspA serotype ST1 to ST6, determined by an IgG binding assay at Day 208 was presented in this outcome measure.
次要结局
- Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Booster Dose(Within 7 days after booster dose)
- Percentage of Participants With Serious Adverse Events (SAEs)(From Day 1 of vaccination up to Day 208 (Month 7))
- Percentage of Participants With Adverse Events of Special Interest (AESIs)(From Day 1 of vaccination up to Day 208 (Month 7))
- Percentage of Participants With Unsolicited Adverse Events(From Day 1 to Day 28 after vaccination 1, 2 and 3 at Month 0, 2 and 6, respectively)
- Percentage of Participants With SAEs, AESIs, Solicited and Unsolicited AEs Stratified by Age Group(SAEs, AESIs: From Day 1 of vaccination (vac) up to Day 208 (Month 7), Solicited AEs: From Day 1 to Day 7 after vac 1, 2 and 3 at Month 0, 2 and 6, respectively; Unsolicited AEs: From Day 1 to Day 28 after vac 1, 2 and 3 at Month 0, 2 and 6, respectively)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) at Baseline, Day 85, Day 180 and Day 194 During the Main Study Phase(Baseline, Day 85, Day 180 and Day 194)
- Seroconversion Rate for Each OspA Serotype (ST1 to ST6) Specific IgG at Day 85, 180, 194 and 208(Day 85, Day 180, Day 194 and Day 208)
- Geometric Mean of the Fold Rise (GMFR) for IgG Against Each OspA Serotype (ST1 to ST6) at Day 85 and Day 208 During the Main Study Phase(Baseline, Day 85 and 208)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Group at Baseline, Day 85, Day 180, Day 194 and Day 208 During the Main Study Phase(Baseline, Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208)
- Seroconversion Rate for Each OspA Serotype (ST1 to ST6) Specific IgG at Day 85, 180, 194 and 208 Stratified by Age Group During the Main Study Phase(Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208)
- Geometric Mean of the Fold Rise (GMFR) for IgG Against Each OspA Serotype (ST1 to ST6) at Day 85, Day 180, Day 194 and Day 208 Stratified by Age Group During the Main Study Phase(Baseline, Day 85, Day 180, Day 194 (18 to 65 years only) and Day 208)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) During the Booster Phase(Up to Month 48)
- SCR for Each OspA Serotype (ST1 to ST6) IgG During the Booster Phase(Up to Month 48)
- GMFR for IgG Against Each OspA Serotype (ST1 to ST6) at Month 19 During the Booster Phase(Month 19)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Cohort During the Booster Phase(Up to Month 48)
- SCR for Each OspA Serotype (ST1 to ST6) IgG Stratified by Age Cohort During the Booster Phase(Up to Month 48)
- GMFR for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Cohort During the Booster Phase(Up to Month 48)
- Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 1 Booster Dose(From Day 1 to Day 7 after vaccination 1 booster dose at Month 18)
- Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 2 Booster Dose(From Day 1 to Day 7 after vaccination 2 booster dose at Month 30)
- Percentage of Participants With Solicited Local and Solicited Systemic AEs Within 7 Days After Vaccination 3 Booster Dose(From Day 1 to Day 7 after vaccination 3 booster dose at Month 42)
- Percentage of Participants With Serious Adverse Events (SAEs)(From Day 1 of vaccination 1 up to 6 months following the last booster dose (up to Month 48))
- Percentage of Participants With Adverse Events of Special Interest (AESIs)(From Day 1 of vaccination 1 up to 6 months following the last booster dose (up to Month 48))
- Percentage of Participants With Unsolicited AE(Up to 28 Days after vaccination 1, 2 or 3 at Month 0, 2 and 6, respectively, and up to 28 Days after vaccination 1, 2 or 3 booster dose at Month 18, 30 and 42, respectively)
- Percentage of Participants With SAEs, AESIs, Solicited and Unsolicited AEs Stratified by Age Group(SAEs & AESIs: From Day 1 of vaccination up to Month 48; Solicited AEs: from Day 1 to Day 7 after vaccination 1, 2, 3, 4, 5 and 6; Unsolicited AEs: up to 28 Days after vaccination 1, 2, 3, 4, 5 and 6)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) at Baseline, Days 85, 180, 365 and Month 18(Baseline; Days 85, 180 and 365; Month 18)
- Seroconversion Rate (SCR) at Days 85, 180, 208, 365 and Month 18(Days 85, 180, 208 and 365; Month 18)
- Geometric Mean of the Fold Rise (GMFR) for IgG When Compared to Baseline Against Each OspA Serotype (ST1 to ST6) at Days 85 and 208(Days 85 and 208)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Group at Baseline, Days 85, 180, 194, 365 and Month 18(Baseline; Days 85, 180, 194 (18 to 65 years only) and 365; Month 18)
- SCR Stratified by Age Group at Days 85, 180, 194, 208, 365 and Month 18(Days 85, 180, 194 (18 to 65 years only), 208 and 365; Month 18)
- GMFR for IgG When Compared to Baseline Against Each OspA Serotype (ST1 to ST6) Stratified by Age Group at Days 85 and 208(Days 85 and 208)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) at Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48(Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48)
- SCR at Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48(Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48)
- GMFR for IgG Against Each OspA Serotype (ST1 to ST6) at Months 19, 31 and 43 During the Booster Phase(Months 19, 31 and 43)
- GMTs for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Group at Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48(Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48)
- SCR Stratified by Age Group at Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48(Months 18, 19, 23, 26, 30, 31, 39, 42, 43 and 48)
- GMFR for IgG Against Each OspA Serotype (ST1 to ST6) Stratified by Age Group at Months 19, 31 and 43 During the Booster Phase(Months 19, 31 and 43)