Safety and Efficacy Study of Vaccine Schedule With Ad26.Mos.HIV and MVA-Mosaic in Human Immunodeficiency Virus (HIV)-Infected Adults

Phase 1

Completed

Conditions: Human Immunodeficiency Virus

Interventions: Biological: Ad26.Mos.HIV
Drug: Placebo
Biological: MVA-Mosaic

Registration Number: NCT02919306

Lead Sponsor: Janssen Vaccines & Prevention B.V.

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine	Ad26.Mos.HIV	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.
Ad26.Mos.HIV Vaccine or MVA mosaic Vaccine	MVA-Mosaic	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.
Placebo	Placebo	0.5 mL Sodium Chloride Injection United States Pharmacopeia (USP) 0.9% will be administered by intramuscular (IM) injection.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Grade 3 or 4 Solicited Systemic AEs	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	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	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	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)	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	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	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	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	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)	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	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	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	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	From Week 60 to Week 96	Percentage of participants with sustained viremic control (HIV RNA \<50 copies/mL) during ATI phase were reported.

Secondary Outcome Measures

Name	Time	Method
Total HIV Deoxyribonucleic Acid (DNA) Levels Over Time	From Week 60 to Week 96	The total HIV DNA levels were assessed as a biomarker of the HIV reservoir.
Time to Reinitiating ART	Up to Week 96	Time to reinitiating ART was reported.
Change in Cluster of Differentiation (CD)4 Count Over Time	Baseline and from Week 60 to Week 96	Change in CD4 count over time was reported. Assessment of residual HIV replication and viral reservoir in total CD4+ T cells was measured by quantitative real-time polymerase chain reaction (PCR).
Number of Participants With Acute Retroviral Syndrome Post-ARV ATI	From Week 60 to Week 96	Number of participants with acute retroviral syndrome post-ARV ATI were reported.
Percentage of Participants With HIV Resistance to ARV Drugs Who Experienced Rebound Viremia After ARV ATI	From Week 60 to Week 96	Percentage of participants with HIV resistance to ARV drugs who experienced rebound viremia after ARV ATI were reported. An HIV genotype test was done to evaluate and characterize HIV resistance to ARV drugs in participants who experience rebound viremia after ARV ATI.
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	Frozen peripheral blood mononuclear cell (PBMCs) was analyzed by interferon-gamma (IFN-gamma) (ELISpot). The response was defined as post-baseline value \>P95 if baseline \<P95 or missing or defined as post-baseline value \>3-fold increase from baseline if baseline \>=P95. The threshold for ELISpot test was based on the 95th percentile (P95) from the baseline values of participants on that test in the study.
Percentage of Env Antibody-dependent Cellular Phagocytosis (ADCP) Glycoprotein (gp) Antibody Over Time	At Week 24, 26, 48 and 50	The functionality of vaccine-induced antibody responses was investigated by the determination of ADCP. The response was defined as post-baseline value \> limit of detection (LOD) if baseline \<LOD or missing or defined as post-baseline value \>3-fold increase from baseline if baseline \>=LOD. The lower limits of detection (LODs) for this assay were 4.28 (phagocytic score) for Mos1.
Percentage of Responders for HIV Neutralizing Antibody (nAb)	Week 64	The functionality of vaccine-induced antibody responses was investigated by the determination of nAb activity in a virus neutralization assay (VNA) using TZM-bl cells and Env-pseudotyped viruses. The response was defined as post-baseline value \>LLOQ.
Duration of Acute Retroviral Syndrome Post-ARV ATI	From Week 60 to Week 96	Duration of acute retroviral syndrome post-ARV ATI was reported.
Percentage of Responders for Envelop (Env) Clade A, B, C and Mos1-specific Binding Antibody Titers	At Week 24, 26, 48 and 50	The Env Clade A (92UG037), B (1990a), and C (Con C), (C97ZA.012) and Mos1- specific binding antibody titer 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 less than (\<) LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline greater than or equal to (\>=) LLOQ. The lower limits of quantification (LLOQs) for this assay were 625, 156.25, 625, 156.25 and 78.125 endotoxin units per milliliter (EU/mL) for Clade A (92UG037), Clade B (1990a), Clade C (Con C), Clade C (C97ZA.012) and Mos1 respectively.
Percentage of Responders for Clade C (C97ZA.012) Env ELISA Immunoglobulin G1 (IgG1), IgG2, and IgG3 Glycoprotein (gp) 140 Binding Antibody	Week 50	Vaccine-induced binding antibody IgG1, IgG2, and IgG3 subclass responses were investigated using Clade C (C97ZA.012) specific ELISAs. The response was defined as post-baseline value \>LLOQ if baseline \<LLOQ or missing or defined as post-baseline value \>3-fold increase from baseline if baseline \>=LLOQ. The LLOQs for this assay were 12.3, 28.7, and 12.4, for IgG1, IgG2, and IgG3, respectively. Less participants were assessed for IgG2 responses due to lack of sample volume which led to a limit on the number of repeats that the analysis lab could perform. Reportable results were not generated for the remaining participants post vaccination.
Breadth of T Cell Responses Analyzed by ELISPOT Assays	Baseline (Week 0), Week 26 and 50	Breadth of T cell responses was assessed at baseline (Week 0), Week 26, and Week 50 by ELISPOT assays.