A Combined Phase 1/2a, Exploratory Study of a Therapeutic Vaccine Using an Adenovirus Type 26 Vector Prime and Modified Vaccinia Ankara Boost Combination With Mosaic Inserts in HIV-1 Infected Adults Who Initiated Antiretroviral Treatment During Acute HIV Infection
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 27
- 主要终点
- Percentage of Participants With Grade 3 or 4 Solicited Systemic AEs
研究概览
简要总结
The purpose of the study is to assess: 1 safety and tolerability of adenovirus serotype 26 (Ad26) prime and Modified Vaccinia Ankara (MVA) boost versus placebo in participants on suppressive antiretroviral therapy (ART) that was initiated during acute Human Immunodeficiency Virus (HIV) infection; 2) Measure the frequency and duration of sustained viremic control after receiving Ad26 prime/MVA boost or placebo, defined as greater than 24 weeks with plasma HIV ribonucleic acid (RNA) lesser than (<)50 copies/ml after antiretroviral (ARV) analytical treatment interruption (ATI).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- 否
入选标准
- •Confirmed human immunodeficiency virus (HIV)-1 infected and started antiretroviral therapy (ART) during acute infection (Fiebig stages I, II, III or IV) as part of trial RV254
- •Treatment with current stable antiretroviral therapy (ART) (no changes to treatment) for at least 4 weeks prior to screening
- •All female participants of childbearing potential must have a negative serum pregnancy test (beta human chorionic gonadotropin) at the screening visit, and a negative urine pregnancy test prior to vaccination on Day 1 and prior to subsequent study vaccinations
- •HIV ribonucleic acid (RNA) less than (<)50 copies per milliliter (copies/ml) for at least 48 weeks at screening: a) One blip of HIV RNA greater than (>)50 and <200 copies/ml within 48 weeks is acceptable, provided that the most recent (before screening) HIV RNA <50 copies/ml
- •Laboratory criteria during screening: a) Hemoglobin: Women: greater than or equal to >=11 gram/deciliter (g/dL); Men >=12.5 g/dL, b) White cell count: 2,500 to 11,000 cells per cubic millimeter (cells/mm^3), c) Platelets: 125,000 to 450,000 per mm^3, d) Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to <=1.5x institutional upper limits of normal (ULN), e) Creatinine <=1.5x institutional ULN, f) CD4 > 400 cells/mm^3, g) Troponin <1x ULN
- •A woman must be either: a) Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 2 years, or any age with amenorrhea for at least 6 months and a serum follicle stimulation hormone [FSH] level >40 International Units Per Liter (IU/L); surgically sterile; or b) Of child-bearing potential and practicing an effective double method of birth control (example, prescription oral contraceptives, contraceptive injections, intrauterine device, contraceptive patch, or vaginal ring, in conjunction with either a female condom or one of the methods for male contraception before entry and through 3 months after the last vaccination
排除标准
- •Receipt of any vaccine within 30 days prior to the first vaccination or plans to receive within 30 days post-vaccination. In the case of medically indicated vaccines, the vaccination should be given at least 2 weeks before or after the first vaccination. However, if a vaccine is indicated in a post exposure setting (example, rabies or tetanus), it must take priority over the study vaccine and same rules will apply to subsequent study vaccinations
- •Any history of HIV-related illness under Centers for Disease Control and Prevention (CDC) category C
- •History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with permanent sequelae, clinically significant arrhythmia (including any arrhythmia requiring medication, treatment, or clinical follow-up)
- •Chronic active hepatitis B or active hepatitis C (for example, positive serology with confirmatory positive polymerase chain reaction) or active syphilis infection. Active syphilis documented by examination or serology unless positive serology is due to past treated infection
- •Receipt of blood products or immunoglobulin in the past 3 months
- •History of anaphylaxis or other serious adverse reactions to vaccines or vaccine products, or neomycin or streptomycin or egg products
- •History of chronic urticaria (recurrent hives)
- •Chronic or recurrent use of medications which modify host immune response, example (e.g.) cancer chemotherapeutic agents, parenteral corticosteroids (short course oral steroids given for non-chronic conditions not expected to recur is not an exclusion criteria, topical steroid use is not an exclusion criteria), etc. but not including ART
研究组 & 干预措施
Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine
Participants will receive adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV) 0.5 milliliter (mL) injection intramuscularly (containing 5 * 10^10 viral particles [vp]) at Weeks 0 and 12 followed by modified Vaccinia Ankara-Mosaic (MVA mosaic) 0.5 mL injection (containing 10^8 Plaque-forming unit [pfu]) at Week 24 and 48.
干预措施: Ad26.Mos.HIV (Biological)
Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine
Participants will receive adenovirus serotype 26-Mosaic -Human Immunodeficiency Virus (Ad26.Mos.HIV) 0.5 milliliter (mL) injection intramuscularly (containing 5 * 10^10 viral particles [vp]) at Weeks 0 and 12 followed by modified Vaccinia Ankara-Mosaic (MVA mosaic) 0.5 mL injection (containing 10^8 Plaque-forming unit [pfu]) at Week 24 and 48.
干预措施: MVA-Mosaic (Biological)
Placebo
0.5 mL Sodium Chloride Injection United States Pharmacopeia (USP) 0.9% will be administered by intramuscular (IM) injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Grade 3 or 4 Solicited Systemic AEs
时间窗: Up to Week 49 (7 days post each vaccination)
Solicited systemic AE of grade 3 or 4 and that is thought to be related to study vaccine were reported. Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching.
Percentage of Participants With Grade 3 or 4 Related AEs
时间窗: Up to Week 52 (28 days after each vaccination)
Related AEs of grade 3 or 4 and that is thought to be related to study vaccine were reported.
Percentage of Participants With Solicited Systemic AEs for 7 Days After Each Vaccination
时间窗: Up to Week 49 (7 days after each vaccination)
Solicited systemic AEs included fever (defined as body temperature of 38.0-degree celsius or higher), fatigue, headache, myalgia, arthralgia, chills, nausea, vomiting, rashes, and general itching were collected and reported for 7 days after each vaccination.
Percentage of Participants With AEs Leading to Discontinuation of Study Vaccination
时间窗: Up to Week 96
Percentage of participants with AEs leading to discontinuation of study vaccination were reported.
Percentage of Participants With Grade 3 or 4 Solicited Local Adverse Events (AEs)
时间窗: Up to Week 49 (7 days post each vaccination)
Solicited local AE of grade 3 or 4 and that is thought to be related to study vaccine were reported. An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. Solicited local AEs (at injection site) included pain/tenderness, erythema, induration, swelling, itching and warmth were collected and reported for 7 days after each vaccination.
Percentage of Participants With Grade 3 or 4 Unsolicited AEs
时间窗: Up to Week 52 (28 days after each vaccination)
Unsolicited AE with worst severity grade 3 or 4 and that is thought to be related to study vaccine were reported. Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.
Percentage of Participants With Solicited Local AEs for 7 Days After Each Vaccination
时间窗: Up to Week 49 (7 days post each vaccination)
An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. Solicited local AEs (at injection site) included pain/tenderness, erythema, induration, swelling, itching and warmth were collected and reported for 7 days after each vaccination.
Percentage of Participants With Worst Laboratory Toxicity Grades 1, 2, 3, and 4 and Non-graded Serum Chemistry Abnormalities
时间窗: Up to Week 96
Percentage of participants with worst laboratory grades 1 (mild), 2 (moderate), 3 (severe), and 4 (potentially life-threatening) and non-graded serum chemistry abnormalities were reported. Serum chemistry parameters included alanine aminotransferase, aspartate aminotransferase, creatine, hyperglycemia, hypoglycemia, gamma-gutamyl transferase, chloride, urea nitrogen, and bilirubin. The parameters not represented in the grading scale, abnormalities were indicated as being 'high' or 'low' or 'abnormal'.
Percentage of Participants With Worst Laboratory Toxicity Grade 1 and Non-graded Hematology Abnormalities
时间窗: Up to Week 96
Percentage of participants with worst laboratory toxicity grade 1 (mild) and non-graded hematology abnormalities were reported. Hematology parameters included absolute neutrophil count, basophils/leukocytes, eosinophils/leukocytes, hematocrit, lymphocytes/leukocytes, monocytes/leukocytes, neutrophils/leukocytes, erythrocytes, hematocrit, neutrophils, basophils, eosinophils, eosinophils/leukocytes, monocytes, neutrophils and platelet count. The parameters not represented in the grading scale, abnormalities were indicated as being 'high' or 'low' or 'abnormal'.
Percentage of Participants With Related AEs and Serious Adverse Events (SAEs)
时间窗: Up to Week 52 (28 days after each vaccination)
An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non-investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment. A SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product.
Duration of Sustained Viremic Control With HIV RNA <50 Copies/mL During ATI Phase
时间窗: From Week 60 to Week 96
Duration of sustained viremic control With HIV RNA \<50 copies/mL during ATI Phase was reported.
Percentage of Participants With Unsolicited AEs 28 Days After Each Vaccination
时间窗: Up to Week 52 (28 days after each vaccination)
Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.
Percentage of Participants With AEs
时间窗: Up to Week 52 (28 days after each vaccination)
Percentage of participants with AEs were reported.
Percentage of Participants With Sustained Viremic Control (Human Immunodeficiency Virus [HIV] Ribonucleic Acid [RNA] Less Than [<]50 Copies Per Milliliter [Copies/mL]) During ATI Phase
时间窗: From Week 60 to Week 96
Percentage of participants with sustained viremic control (HIV RNA \<50 copies/mL) during ATI phase were reported.
次要结局
- Total HIV Deoxyribonucleic Acid (DNA) Levels Over Time(From Week 60 to Week 96)
- Time to Reinitiating ART(Up to Week 96)
- Change in Cluster of Differentiation (CD)4 Count Over Time(Baseline and from Week 60 to Week 96)
- Number of Participants With Acute Retroviral Syndrome Post-ARV ATI(From Week 60 to Week 96)
- Percentage of Participants With HIV Resistance to ARV Drugs Who Experienced Rebound Viremia After ARV ATI(From Week 60 to Week 96)
- Percentage of Responders With Interferon-gamma (IFN-gamma) T Cell Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) at Week 24, 26, 48, and 50(At Week 24, 26, 48 and 50)
- Percentage of Env Antibody-dependent Cellular Phagocytosis (ADCP) Glycoprotein (gp) Antibody Over Time(At Week 24, 26, 48 and 50)
- Percentage of Responders for HIV Neutralizing Antibody (nAb)(Week 64)
- Duration of Acute Retroviral Syndrome Post-ARV ATI(From Week 60 to Week 96)
- Percentage of Responders for Envelop (Env) Clade A, B, C and Mos1-specific Binding Antibody Titers(At Week 24, 26, 48 and 50)
- Percentage of Responders for Clade C (C97ZA.012) Env ELISA Immunoglobulin G1 (IgG1), IgG2, and IgG3 Glycoprotein (gp) 140 Binding Antibody(Week 50)
- Breadth of T Cell Responses Analyzed by ELISPOT Assays(Baseline (Week 0), Week 26 and 50)