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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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Janssen Vaccines & Prevention B.V.
ClinicalTrials.gov Identifier:
NCT02919306
First received: September 1, 2016
Last updated: February 20, 2017
Last verified: February 2017
  Purpose
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 Intervention Phase
Human Immunodeficiency Virus (HIV)
Biological: Ad26.Mos.HIV
Biological: MVA-Mosaic
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Janssen Vaccines & Prevention B.V.:

Primary Outcome Measures:
  • Number of Participants With Vaccine Related - Grade 3 or Greater Reactogenicity and Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Day 1 through Week 96 ]
  • Number of Participants With Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) less than (<)50 copies per milliliter (copies/ml) at 24 Weeks After Antiretroviral (ARV) Analytical Treatment Interruption (ATI) [ Time Frame: Week 60 ]

Secondary Outcome Measures:
  • Cell-Associated HIV RNA in Total Cluster of Differentiation (CD)4+ Thymus (T) Cells [ Time Frame: Week 96 ]
    Assessment of residual HIV replication and viral reservoir in total CD4+ T cells as measured by quantitative real-time polymerase chain reaction (PCR).

  • Cell-Associated HIV RNA in the Memory CD4 Subsets [ Time Frame: Week 96 ]
    Assessment of residual HIV replication and viral reservoir in memory CD4+T cells as measured by quantitative real-time PCR.

  • Cell-Associated Human Immunodeficiency Virus Deoxyribonucleic Acid (HIV DNA) (total, integrated and 2 Long Terminal Repeats [LTR] Circles) in Total CD4+ T Cells [ Time Frame: Week 96 ]
    Assessment of the viral reservoir in total CD4+ T cells as measured by total and integrated HIV DNA and by 2-LTR circles.

  • Cell-Associated HIV DNA (Total, Integrated and 2 LTR Circles) in the Memory CD4 Subsets [ Time Frame: Week 96 ]
    Assessment of the viral reservoir in memory CD4+ T cells as measured by total and integrated HIV DNA and by 2-LTR circles.

  • Quantification of Latent HIV in Total CD4+ T Cells Using a Viral Outgrowth Assay [ Time Frame: Week 96 ]
    Quantitative viral outgrowth assay (QVOA) performed on participants undergoing leukapheresis and only if plasma HIV-1 RNA viral load less than (<)50 copies/mL to evaluate the viral outgrowth.

  • Quantification of Latent HIV in Memory CD4+ T Cells Using a Viral Outgrowth Assay [ Time Frame: Week 96 ]
  • Quantification of the Size of the Inducible Viral Reservoir in Total CD4+ T Cells [ Time Frame: Week 96 ]
    Measurement of the magnitude of the inducible viral reservoir will be done using the tat/rev induced limiting dilution assay (TILDA) using total CD4+ T cells.

  • Quantification of the Size of the Inducible Viral Reservoir in Memory CD4+ T Cells [ Time Frame: Week 96 ]
    Measurement of the magnitude of the inducible viral reservoir will be done using the tat/rev induced limiting dilution assay (TILDA) using memory CD4+ T cells.

  • Single Copy HIV RNA in Samples With HIV RNA <50 copies per milliliter (copies/ml) pre and post Antiretroviral (ARV) Analytical Treatment Interruption (ATI) [ Time Frame: Week 96 ]
  • Frequency of Epitope Recognition by Enzyme-Linked Immunospot (ELISPOT) [ Time Frame: Week 96 ]
    Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme linked immunospot assay (ELISPOT) with mapping of positive pools to determine the number of positive epitopes.

  • Magnitude of Epitope Recognition by Enzyme-Linked Immunospot (ELISPOT) [ Time Frame: Week 96 ]
    Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme-linked immunospot assay (ELISPOT) with mapping of positive pools to determine the number of positive epitopes.

  • Breadth of Epitope Recognition by Enzyme-Linked Immunospot (ELISPOT) [ Time Frame: Week 96 ]
    Assays of peptide pool sets covering the Gag, Env or Pol will be evaluated by standard enzyme-linked immunospot assay (ELISPOT) with mapping of positive pools to determine the number of positive epitopes.

  • Polyfunctionality of Thymus (T) cell Responses [ Time Frame: Week 96 ]
    Polyfunctionality of T cell responses allow correlations to reveal the critical information on therapeutic vaccination and treatment interruption and evaluation of immunogenicity.

  • Number of Binding Antibody to Envelope (Env) Regions [ Time Frame: Week 96 ]
    Binding antibody to immunogen inserts and a panel of HIV envelope proteins representing the circulating HIV-1 strains will assess the immunogenicity.

  • Breadth of antibody neutralization across different HIV-1 strains from different clades will assess immunogenicity as measured in the TZM-bl neutralization assay [ Time Frame: Week 96 ]
    Inducing potent neutralizing antibodies (that are group specific and capable of neutralizing all isolates of HIV-1) will evaluate the immunogenicity.


Enrollment: 27
Study Start Date: September 2016
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02919306

Locations
Thailand
Bangkok, Thailand
Sponsors and Collaborators
Janssen Vaccines & Prevention B.V.
Investigators
Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial Janssen Vaccines & Prevention B.V.
  More Information

Responsible Party: Janssen Vaccines & Prevention B.V.
ClinicalTrials.gov Identifier: NCT02919306     History of Changes
Other Study ID Numbers: CR108161
VAC89220HTX1001 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
Study First Received: September 1, 2016
Last Updated: February 20, 2017

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 23, 2017