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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02919306
Recruitment Status : Completed
First Posted : September 29, 2016
Results First Posted : March 11, 2022
Last Update Posted : March 11, 2022
Sponsor:
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Biological: Ad26.Mos.HIV Biological: MVA-Mosaic Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 2016
Actual Primary Completion Date : September 2018
Actual Study Completion Date : September 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Biological: Ad26.Mos.HIV
Recombinant replication-deficient Ad26 vectored vaccine and consists of 3 Ad26 vectors, one containing a mosaic insert of envelope (Env) sequence, and 2 vectors containing mosaic inserts of Gag and Pol sequences (Ad26.Mos.1.Env + Ad26.Mos1.Gag-Pol + Ad26.Mos2.Gag-Pol). Total dose is 5*10^10 viral particle per 0.5 milliliter (mL) injection administered intramuscularly.

Biological: MVA-Mosaic
Recombinant live attenuated MVA virus-vectored vaccine that has been genetically engineered to express 2 mosaic Gag, Pol, and Env sequences (Mosaic 1 and Mosaic 2). Total dose is 10^8 plaque-forming unit per 0.5 mL injection administered intramuscularly.

Placebo Comparator: Placebo
0.5 mL Sodium Chloride Injection United States Pharmacopeia (USP) 0.9% will be administered by intramuscular (IM) injection.
Drug: Placebo
Participants will receive placebo intramuscularly Weeks 0, 12, 24 and 48.




Primary Outcome Measures :
  1. Percentage of Participants With Grade 3 or 4 Solicited Local Adverse Events (AEs) [ Time Frame: 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.

  2. Percentage of Participants With Grade 3 or 4 Solicited Systemic AEs [ Time Frame: 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.

  3. Percentage of Participants With Grade 3 or 4 Unsolicited AEs [ Time Frame: 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.

  4. Percentage of Participants With Grade 3 or 4 Related AEs [ Time Frame: 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.

  5. Percentage of Participants With Solicited Local AEs for 7 Days After Each Vaccination [ Time Frame: 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.

  6. Percentage of Participants With Solicited Systemic AEs for 7 Days After Each Vaccination [ Time Frame: 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.

  7. Percentage of Participants With Unsolicited AEs 28 Days After Each Vaccination [ Time Frame: Up to Week 52 (28 days after each vaccination) ]
    Unsolicited AEs were defined as events that participants experienced but were not specifically asked about.

  8. Percentage of Participants With Related AEs and Serious Adverse Events (SAEs) [ Time Frame: 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.

  9. Percentage of Participants With AEs Leading to Discontinuation of Study Vaccination [ Time Frame: Up to Week 96 ]
    Percentage of participants with AEs leading to discontinuation of study vaccination were reported.

  10. Percentage of Participants With AEs [ Time Frame: Up to Week 52 (28 days after each vaccination) ]
    Percentage of participants with AEs were reported.

  11. Percentage of Participants With Worst Laboratory Toxicity Grades 1, 2, 3, and 4 and Non-graded Serum Chemistry Abnormalities [ Time Frame: 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'.

  12. Percentage of Participants With Worst Laboratory Toxicity Grade 1 and Non-graded Hematology Abnormalities [ Time Frame: 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'.

  13. 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 [ Time Frame: From Week 60 to Week 96 ]
    Percentage of participants with sustained viremic control (HIV RNA <50 copies/mL) during ATI phase were reported.

  14. Duration of Sustained Viremic Control With HIV RNA <50 Copies/mL During ATI Phase [ Time Frame: From Week 60 to Week 96 ]
    Duration of sustained viremic control With HIV RNA <50 copies/mL during ATI Phase was reported.


Secondary Outcome Measures :
  1. Total HIV Deoxyribonucleic Acid (DNA) Levels Over Time [ Time Frame: From Week 60 to Week 96 ]
    The total HIV DNA levels were assessed as a biomarker of the HIV reservoir.

  2. Change in Cluster of Differentiation (CD)4 Count Over Time [ Time Frame: 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).

  3. Time to Reinitiating ART [ Time Frame: Up to Week 96 ]
    Time to reinitiating ART was reported.

  4. Number of Participants With Acute Retroviral Syndrome Post-ARV ATI [ Time Frame: From Week 60 to Week 96 ]
    Number of participants with acute retroviral syndrome post-ARV ATI were reported.

  5. Duration of Acute Retroviral Syndrome Post-ARV ATI [ Time Frame: From Week 60 to Week 96 ]
    Duration of acute retroviral syndrome post-ARV ATI was reported.

  6. Percentage of Participants With HIV Resistance to ARV Drugs Who Experienced Rebound Viremia After ARV ATI [ Time Frame: 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.

  7. 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 [ Time Frame: 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.

  8. Percentage of Responders for Envelop (Env) Clade A, B, C and Mos1-specific Binding Antibody Titers [ Time Frame: 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.

  9. Percentage of Responders for Clade C (C97ZA.012) Env ELISA Immunoglobulin G1 (IgG1), IgG2, and IgG3 Glycoprotein (gp) 140 Binding Antibody [ Time Frame: 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.

  10. Breadth of T Cell Responses Analyzed by ELISPOT Assays [ Time Frame: 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.

  11. Percentage of Env Antibody-dependent Cellular Phagocytosis (ADCP) Glycoprotein (gp) Antibody Over Time [ Time Frame: 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.

  12. Percentage of Responders for HIV Neutralizing Antibody (nAb) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02919306


Locations
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Thailand
Bangkok, Thailand
Sponsors and Collaborators
Janssen Vaccines & Prevention B.V.
Investigators
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Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial Janssen Vaccines & Prevention B.V.
  Study Documents (Full-Text)

Documents provided by Janssen Vaccines & Prevention B.V.:
Study Protocol  [PDF] October 11, 2017
Statistical Analysis Plan  [PDF] October 17, 2018

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Janssen Vaccines & Prevention B.V.
ClinicalTrials.gov Identifier: NCT02919306    
Other Study ID Numbers: CR108161
VAC89220HTX1001 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
First Posted: September 29, 2016    Key Record Dates
Results First Posted: March 11, 2022
Last Update Posted: March 11, 2022
Last Verified: December 2021

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Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Blood-Borne Infections
Communicable Diseases
Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Slow Virus Diseases