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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

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ClinicalTrials.gov Identifier: NCT02919306
Recruitment Status : Completed
First Posted : September 29, 2016
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Vaccines & Prevention B.V.

Tracking Information
First Submitted Date  ICMJE September 1, 2016
First Posted Date  ICMJE September 29, 2016
Last Update Posted Date September 20, 2019
Actual Study Start Date  ICMJE October 2016
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2016)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2016)
  • 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 immnunogenicity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Vaccine Schedule With Ad26.Mos.HIV and MVA-Mosaic in Human Immunodeficiency Virus (HIV)-Infected Adults
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Human Immunodeficiency Virus
Intervention  ICMJE
  • 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.
  • Drug: Placebo
    Participants will receive placebo intramuscularly Weeks 0, 12, 24 and 48.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: Ad26.Mos.HIV
    • Biological: MVA-Mosaic
  • Placebo Comparator: Placebo
    0.5 mL Sodium Chloride Injection United States Pharmacopeia (USP) 0.9% will be administered by intramuscular (IM) injection.
    Intervention: Drug: Placebo
Publications * Colby DJ, Sarnecki M, Barouch DH, Tipsuk S, Stieh DJ, Kroon E, Schuetz A, Intasan J, Sacdalan C, Pinyakorn S, Grandin P, Song H, Tovanabutra S, Shubin Z, Kim D, Paquin-Proulx D, Eller MA, Thomas R, de Souza M, Wieczorek L, Polonis VR, Pagliuzza A, Chomont N, Peter L, Nkolola JP, Vingerhoets J, Truyers C, Pau MG, Schuitemaker H, Phanuphak N, Michael N, Robb ML, Tomaka FL, Ananworanich J. Safety and immunogenicity of Ad26 and MVA vaccines in acutely treated HIV and effect on viral rebound after antiretroviral therapy interruption. Nat Med. 2020 Apr;26(4):498-501. doi: 10.1038/s41591-020-0774-y. Epub 2020 Mar 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 17, 2016)
27
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2016)
36
Actual Study Completion Date  ICMJE September 2018
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02919306
Other Study ID Numbers  ICMJE CR108161
VAC89220HTX1001 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Janssen Vaccines & Prevention B.V.
Study Sponsor  ICMJE Janssen Vaccines & Prevention B.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial Janssen Vaccines & Prevention B.V.
PRS Account Janssen Vaccines & Prevention B.V.
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP