A Randomized, Parallel-Group, Placebo-Controlled, Double-Blind Phase 1/2a Study in Healthy HIV Uninfected Adults to Assess the Safety/Tolerability and Immunogenicity of 2 Different Prime/Boost Regimens; Priming With Trivalent Ad26.Mos.HIV and Boosting With Trivalent Ad26.Mos.HIV And Clade C Gp140 Plus Adjuvant or Priming With Tetravalent Ad26.Mos4.HIV and Boosting With Tetravalent Ad26.Mos4.HIV and Clade C Gp140 Plus Adjuvant
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 201
- 主要终点
- Percentage of Participants With Solicited Local AEs Post Third Vaccination
研究概览
简要总结
The purpose of this study is to assess the safety/tolerability of the 2 different vaccine regimens of priming with trivalent Ad26.Mos.HIV and boosting with trivalent Ad26.Mos.HIV and Clade C gp140 plus adjuvant or priming with tetravalent Ad26.Mos4.HIV and boosting with Ad26.Mos4.HIV and Clade C glycoprotein (gp)140 plus adjuvant. Immune responses of the different vaccine schedules will be assessed.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Are negative for human immunodeficiency virus (HIV) infection at screening
- •Is healthy on the basis of physical examination, medical history, electrocardiogram (ECG), and vital signs measurement performed at screening
- •Are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures
- •Female participants of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin [beta hCG]) at the Screening visit, and a negative urine pregnancy test pre-dose on Day 1
- •Are assessed by the clinic staff as being at low risk for HIV infection
排除标准
- •Has chronic hepatitis B (measured by hepatitis B surface antigen test) or active hepatitis C (measured by hepatitis C virus [HCV] Ab test; if positive, HCV ribonucleic acid [RNA] PCR test will be used to confirm active versus past HCV infection), active syphilis infection, chlamydia, gonorrhea, or trichomonas . Active syphilis documented by serology unless positive serology is due to past treated infection
- •Has had a thyroidectomy or active thyroid disease requiring medication during the last 12 months (not excluded: a stable thyroid supplementation)
- •Has had major psychiatric illness and/or substance abuse problems during the past 12 months (including hospitalization or periods of work disability) that in the opinion of the investigator would preclude participation
- •Has been in receipt of any licensed vaccine within 14 days prior to the first dose of study vaccine/placebo, plans to receive within 14 days after the first study vaccination, or plans to receive within 14 days before or after the second, third or fourth vaccination
- •Is a recipient of a prophylactic or therapeutic HIV vaccine candidate at any time, or a recipient of other experimental vaccine(s) within the last 12 months prior to the Day 1 visit (Vaccination 1). For participants who received an experimental vaccine (except HIV vaccine) more than 12 months prior to the Day 1 visit (Vaccination 1), documentation of the identity of the experimental vaccine must be provided to the sponsor, who will determine eligibility on a case-by-case basis
研究组 & 干预措施
Group 1B: Placebo
Participants will receive placebo at Weeks 0, 12, 24 and 48.
干预措施: Placebo (Drug)
Group 1A: Ad26.Mos.HIV
Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12, followed by Ad26.Mos.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 micrograms (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48.
干预措施: Ad26.Mos.HIV (Biological)
Group 1A: Ad26.Mos.HIV
Participants will receive Ad26.Mos.HIV vaccine at Week 0 and 12, followed by Ad26.Mos.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 micrograms (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48.
干预措施: Clade C gp140 (Biological)
Group 2A: Ad26.Mos4.HIV
Participants will receive Ad26.Mos4.HIV vaccine at Week 0 and 12; followed by Ad26.Mos4.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 micrograms (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48. Participants will be included in an optional Long-term Extension (LTE) phase (3 years or 4 years Follow-up after Week 72, every 6 months visit) to assess immunogenicity and safety (serious adverse events [SAEs]).
干预措施: Ad26.Mos4.HIV (Biological)
Group 2A: Ad26.Mos4.HIV
Participants will receive Ad26.Mos4.HIV vaccine at Week 0 and 12; followed by Ad26.Mos4.HIV vaccine + Clade C glycoprotein 140 vaccine containing 250 micrograms (mcg) of total protein mixed with adjuvant (aluminum phosphate) at Week 24 and 48. Participants will be included in an optional Long-term Extension (LTE) phase (3 years or 4 years Follow-up after Week 72, every 6 months visit) to assess immunogenicity and safety (serious adverse events [SAEs]).
干预措施: Clade C gp140 (Biological)
Group 2B: Placebo
Participants will receive placebo at Weeks 0, 12, 24 and 48.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Solicited Local AEs Post Third Vaccination
时间窗: 7 days after third vaccination on Day 169 (Day 176)
Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination.
Percentage of Participants With Solicited Local Adverse Events (AEs) Post First Vaccination
时间窗: 7 days after first vaccination on Day 1 (Day 8)
Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination.
Percentage of Participants With Solicited Local AEs Post Second Vaccination
时间窗: 7 days after second vaccination on Day 85 (Day 92)
Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination.
Percentage of Participants With Solicited Local AEs Post Fourth Vaccination
时间窗: 7 days after fourth vaccination on Day 337 (Day 344)
Solicited local AEs were predefined local events (at the injection site: erythema, induration, swelling, itching and warmth) that were by definition considered as related to the study vaccine and collected within 7 days after vaccination.
Percentage of Participants With Solicited Systemic AEs Post First Vaccination
时间窗: 7 days after first vaccination on Day 1 (Day 8)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination.
Percentage of Participants With Solicited Systemic AEs Post Second Vaccination
时间窗: 7 days after second vaccination on Day 85 (Day 92)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination.
Percentage of Participants With Solicited Systemic AEs Post Third Vaccination
时间窗: 7 days after third vaccination on Day 169 (Day 176)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination.
Percentage of Participants With Solicited Systemic AEs Post Fourth Vaccination
时间窗: 7 days after fourth vaccination on Day 337 (Day 344)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Solicited systemic AEs including pyrexia/fever, headache, fatigue, myalgia, nausea and chills were collected within 7 days after vaccination.
Percentage of Participants With Unsolicited AEs for 28 Days After First Vaccination
时间窗: 28 days after first vaccination on Day 1 (Day 29)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as "solicited AEs" and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days.
Percentage of Participants With Unsolicited AEs for 28 Days After Second Vaccination
时间窗: 28 days after second vaccination on Day 85 (Day 113)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as "solicited AEs" and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days.
Percentage of Participants With Unsolicited AEs for 28 Days After Third Vaccination
时间窗: 28 days after third vaccination on Day 169 (Day 197)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as "solicited AEs" and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days.
Percentage of Participants With Unsolicited AEs for 28 Days After Fourth Vaccination
时间窗: 28 days after fourth vaccination on Day 334 (Day 362)
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. Unsolicited AEs were defined as the AEs other than those categorized as "solicited AEs" and were required to be collected for any events that occurred from the time of vaccination and through the subsequent 28 days.
Percentage of Participants With Discontinuations From Vaccination Due to AEs
时间窗: Up to Week 72
Percentage of participants with discontinuations from vaccination due to AEs were reported.
Percentage of Participants With Serious Adverse Events (SAEs) During Main Study
时间窗: Up to Week 72
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. SAE was defined as any AE that resulted in: death, persistent or significant disability/incapacity, required inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, was a congenital anomaly/birth defect and would jeopardize participant and/or required medical or surgical intervention to prevent one of the outcomes listed above.
Percentage of Participants With SAEs During Long Term Extension (LTE) Period
时间窗: From Week 96 to Week 264
An AE was defined as any untoward medical event that occurred in a participant administered an investigational product, and it did not necessarily indicated only events with clear causal relationship with the relevant investigational product. SAE was defined as any AE that resulted in: death, persistent or significant disability/incapacity, required inpatient hospitalization or prolongation of existing hospitalization, was life-threatening experience, was a congenital anomaly/birth defect and would jeopardize participant and/or required medical or surgical intervention to prevent one of the outcomes listed above. This outcome measure was planned to be analyzed for specified arm only.
Percentage of Participants With AEs of Special Interest During Main Study
时间窗: Up to Week 72
Percentage of participants with AEs of special interest during main study were reported. HIV infection was considered as an AE of special interest.
Percentage of Participants With AEs of Special Interest During LTE Period
时间窗: From Week 96 to Week 264
Percentage of participants with AEs of special interest during LTE period were reported. HIV infection was considered as an AE of special interest. This outcome measure was planned to be analyzed for specified arm only.
Percentage of Responders for Envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) Specific Binding Antibody Titers at Week 28
时间窗: Week 28
Percentage of responders for envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) specific binding antibody titers at Week 28 were reported. Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)-specific binding antibody titers were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (\>) lower limit of quantification (LLOQ) if baseline value less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline value greater than or equal to (\>=) LLOQ.
Percentage of Responders for Envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) Specific Binding Antibody Titers at Week 52
时间窗: Week 52
Percentage of responders for envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) specific binding antibody titers at Week 52 were reported. Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)-specific binding antibody titers were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (\>) lower limit of quantification (LLOQ) if baseline value less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline value greater than or equal to (\>=) LLOQ.
Percentage of Responders for Envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) Specific Binding Antibody Titers at Week 72
时间窗: Week 72
Percentage of responders for envelop (Env) Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012) specific binding antibody titers at Week 72 were reported. Env Clade A (92UG037.1), B (1990a), and C (Con C), (C97ZA.012)-specific binding antibody titers were assessed using enzyme-linked immunosorbent assay (ELISA). The response was defined as post-baseline value greater than (\>) lower limit of quantification (LLOQ) if baseline value less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline value greater than or equal to (\>=) LLOQ.
次要结局
- Percentage of Responders for Human Immunodeficiency Virus Neutralizing Antibody (HIV nAb)(Weeks 28, 52 and 72)
- Percentage of Responders for Immunoglobulin G1 (IgG1) and IgG3 Gylcoprotein (gp) 140 Binding Antibody Assessed Using Clade C (C97ZA.012) Env Enzyme-linked Immunosorbent Assay (ELISA)(Weeks 28, 52 and 72)
- Percentage of Responders for CD4+ and CD8+ T-Cell Responses(Weeks 28, 52 and 72)
- Percentage of Responders for Env Antibody-dependent Cellular Phagocytosis (ADCP) gp Antibody(Weeks 28, 52 and 72)
- Percentage of Responders With Interferon-gamma (IFN-gamma) T Cell Responses Assessed Using Enzyme-linked Immunospot Assay (ELISpot)(Weeks 26, 52 and 72)
- Percentage of Participants With T-cell Development(Up to Week 264)