HVTN satellite 21 st July 2019 HIV Vaccine efficacy studies and the MOSAICO clinical trial Disclosure I have the following conflicts of interest to declare I am an employee of Janssen Vaccines amp Prevention BV a pharmaceutical company of Johnson amp Johnson ID: 1043712
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1. Sabrina Spinosa GuzmanJanssen Protocol Chair HVTN satellite21st July 2019HIV Vaccine efficacy studies and the MOSAICO clinical trial
2. DisclosureI have the following conflicts of interest to declare: I am an employee of Janssen Vaccines & Prevention B.V., a pharmaceutical company of Johnson & JohnsonI hold equity shares in Johnson & Johnson
3. Towards a globalHIV vaccine
4. Clade diversityTransmission modeUse of PrEPConsiderations forefficacyevaluation
5. D. Stieh: Tue, 23 Jul Palacio de Valparaíso 2Session: 16:30-18:00F. Tomaka: Tue, 23 Jul Casa Montejo 1 Session: 14:30-16:00Clinical development plan201420152016201720182019202020212022201420152016201720182020202220192021NHP #13-19 Ph2a TRAVERSE N=198 Ph2a ASCENT N=150Ad26.Mos4.HIV vs Ad26.Mos.HIVBoost with Clade C+Mos gp140 vs Clade C alone2023Ph2a APPROACH N=393FIH Ad26.Mos.HIV and heterologous regimens Ph2b IMBOKODO N=2,637 Ph3 MOSAICO N=3,800
6. IMBOKODOPh2bMOSAICOPh3Predominantly Clade CPredominantly Clade BHeterosexual WomenMSM + TGIntra-vaginal transmissionIntra-rectal transmissionSouthern AfricaAmericas, EuropeLimited PrEP useIncreased PrEP use
7. IMBOKODOHPX2008/HVTN705 A phase 2b multicenter, randomized, parallel group, placebo-controlled, double-blind clinical trial.
8. IMBOKODO - Study designFollow upMonth 24Primary analysisN=2,600 women, 1:1 randomization, +/- 1.5 year recruitmentVacc 1Mo 0 Vacc 3Mo 6GroupN11,300Ad26.Mos4.HIVAd26.Mos4.HIV Ad26.Mos4.HIV, CladeC gp140Ad26.Mos4.HIV, CladeC gp14021,300PlaceboPlaceboPlaceboPlaceboVacc 2Mo 3 Vacc 4Mo 12Study completionFollow upMonth 36
9. Primary Objectives and Endpoints Primary ObjectivesTo evaluate the preventive vaccine efficacy (VE) for the prevention of HIV infection in HIV-seronegative women residing in sub-Saharan Africa from confirmed HIV-1 infections diagnosed between the Month 7 and Month 24 visits.To evaluate the safety and tolerability of a heterologous regimen for the prevention of HIV infection in HIV-seronegative women.Primary EndpointsVaccine efficacy as derived from confirmed HIV-1 infections diagnosed between the Month 7 and Month 24 visits.Local and systemic reactogenicity after each vaccination.Serious adverse events, AESIs, and adverse events leading to discontinuation for the entire duration of the study.
10. Ph2b IMBOKODO N=2,600Clinical development plan201420152016201720182019202020212022201420152016201720182020202220192021NHP #13-19 Ph2a TRAVERSE N=198 Ph2a ASCENT N=150Ad26.Mos4.HIV vs Ad26.Mos.HIVBoost with Clade C+Mos gp140 vs Clade C alone2023Ph2a APPROACH N=393FIH Ad26.Mos.HIV and heterologous regimens Ph3 MOSAICO N=3,800
11. MOSAICOHPX3002/HVTN706A Multi-center, Randomized, Double-blind, Placebo-controlled Phase 3 Efficacy Study of a Heterologous Vaccine Regimen of Ad26.Mos4.HIV and Adjuvanted Clade C gp140 and Mosaic gp140 to Prevent HIV-1 Infection Among Cis-gender Men and Transgender Individuals who Have Sex with Cis-gender Men and/or Transgender Individuals.
12. MOSAICO - Study designFollow‑upHIV-1 negative: ≥24 m after 3rd vaccinationHIV-1 positive: 6 m after diagnosisFollow upMonth 24-30Primary analysis3,800 participants; 1:1 randomization (stratified by site)Vacc 1Mo 0 Vacc 3Mo 6GroupN11,900Ad26.Mos4.HIVAd26.Mos4.HIV Ad26.Mos4.HIV, CladeC + Mosaic gp140Ad26.Mos4.HIV, CladeC + Mosaic gp14021,900PlaceboPlaceboPlaceboPlaceboVacc 2Mo 3 Vacc 4Mo 12
13. Primary Objective and Endpoint Primary ObjectiveTo evaluate the vaccine efficacy (VE) for the prevention of HIV-1 infection in HIV-1 seronegative cis-gender men and transgender individuals having sex with cis-gender men and/or transgender individuals.Primary EndpointConfirmed HIV-1 infections diagnosed between Month 7 and Month x (with 24≤x≤30 months) visits in the per-protocol (PP) population.
14. Secondary ObjectivesSecondary ObjectivesTo evaluate the safety and reactogenicity.To evaluate VE at other timepoints and in other analysis populations.To evaluate the immune responses elicited by the vaccine regimen.To evaluate VE by and adjusting for potential (baseline) confounders.
15. Main inclusion criteriaHIV-uninfected cis-gender men and transgender individuals having sex with cis-gender men and/or transgender individuals who are considered to be at increased risk for HIV infection. Participants must in the last 6 months have had:Any condomless receptive anal or vaginal sex (not included is condomless anal sex within a mutually monogamous relationship ≥12 months if the partner is HIV negative or living with HIV and virally suppressed), ORRectal or urethral gonorrhea or chlamydia or incident syphilis, ORAny stimulant use (eg, cocaine, amphetamine), OR5 or more sex partners Potential participant is negative for HIV-1 and HIV-2 infection <28 days prior to first vaccination.
16. Main exclusion criteriaPotential participant shares needles during injection of drugs or any other substance.Potential participant choosing to use PrEPNote: Once participants received the first vaccination, they can decide at any time to initiate PrEP, while remaining in the study. The use of long acting PrEP is disallowed from 24 months prior to Day 1.
17. HIV prevention in the studyAll participants will be offered comprehensive prevention methods:Risk reduction counselingCondom and lubricant provisionPre-Exposure prophylaxis counseling, referral, and linkagePost Exposure prophylaxis counseling referral, and linkageSTI screening, access to treatment and referralThe trial will allow some comparison of the Vaccine + Standard Prevention package vs. Standard Prevention package alone
18. Global site distributionArgentina: 4USA: 24Mexico: 3Peru: 5Brazil: 9Poland: 3Spain: 6Italy: 3EuropeAmericas
19. 0 months3679121315-30FU After 30VaccinationHIV testQ3moQ3moHumoralQ6moCellularChlamydia/GonorrheaQ6moQ6moSyphilisQ6moQ6moSafetySolicitedUnsolicited Solicited UnsolicitedSolicited UnsolicitedSolicited UnsolicitedSafetyContinuouslyOverview of Study Evaluations
20. Efficacy EvaluationsAn HIV test will be performed approximately every 3 months. Testing will be performed according to a sponsor-approved HIV testing algorithm that differentiates VISP from true HIV infection. Flexibility is given for additional HIV tests as unscheduled visits.Participants should refrain from performing any HIV testing outside of the study protocol. Participant with a confirmed positive HIV test during the study, will remain in the study but NO further vaccinations will be administered.A blinded endpoint adjudication process will be in place.
21. Participant Reported OutcomesSexual Activity QuestionnaireAssess determinants of HIV acquisition throughout the study as well as information on HIV testing outside the study. Questionnaire on the Use of Oral PrEP Information on use of and adherence to PrEP. Social Impact Questionnaire Problems experienced with personal relationships, employment, education, health care, housing, health, disability or life insurance, travel, and immigration. Vaccine regimen acceptability
22. Evaluation HIV infected individualsParticipants will remain in the study but NO further vaccinations will be administered. The participant will be followed‑up until approximately 6 months after the diagnosis. Referral to a local clinic for medical treatment and follow-up.Time and eventsEventConfirm36ExitHIV testHIV VLCD4ARTSocial ImpactCounselHumoral/Cellular
23. IMBOKODOPh2bMOSAICOPh3Predominantly Clade CPredominantly Clade BHeterosexual WomenMSM + TGIntra-vaginal transmissionIntra-rectal transmissionSouthern AfricaAmericas, EuropeLimited PrEP useIncreased PrEP useFully enrolled Q2 2019Start Q3 2019
24. HPX3002/HVTN 706 Protocol Team AcknowledgementsJanssen TeamSabrina Spinosa Guzman, Protocol Leadership ChairLudo Lavreys, Study Responsible Physician Vicky Cárdenas, Study Responsible ScientistFrank Tomaka, Franchise Clinical LeaderMaria Grazia Pau, Compound Development Team LeaderCarla Truyers, Study StatisticianSteven Nijs, Clinical Team Statistical LeadDaniel Stieh, Biomarkers LeadZelda Euler, Senior ScientistWolf Ribbens, Senior Associate ScientistRaphaele Roten, Medical Safety OfficerLorenz Scheppler, Global Regulatory AffairsOlive Yuan, Associate Director Data Management Caroline Hodin, Global Data Manager SpecialistWouter Vandermeiren, Senior Global Data ManagerChris McShane, GCDO Clinical Program LeaderKaren Buleza, GCDO Clinical Trial Leader Johan De Decker, Senior Clinical Trial ManagerCornelia Linthicum, Senior Clinical Trial ManagerEveline Hoste, Associate Director Reg Medical WritingAnick Vandingenen, Associate Dir. Reg Medical WritingCorina Ramers-Verhoeven, Global Communication Leader, Vaccines R&D
25. HPX3002/HVTN 706 Protocol Team AcknowledgementsHVTN TeamLarry Corey, Principal InvestigatorJim Kublin, Principal Staff ScientistSusan Buchbinder, HVTN ChairPhilipp Mann, Protocol Team LeaderMegan Jones, Clinical Safety SpecialistRobert De La Grecca, Regional Medical LiaisonIndia Tindale, Clinical Trials ManagerNiles Eaton, Director of Site OperationsLaurie Rinn, Regulatory AssociateMariel Franklin, Regulatory Project ManagerStephaun Wallace, Sen Community Engagement Project ManagerAziel Gangerdine, Director of CommunicationSteven Wakefield, Director of External RelationsDAIDSJulia Hutter, Medical OfficerLabJohn Hural, Associate Director of Laboratory OperationsMike Stirewalt, Quality Assurance Program ManagerKatheryn Dougherty, Quality Assurance AssociateJennifer Hanke, Protocol Operations CoordinatorLisa Sanders, Protocol Operations CoordinatorSCHARPJessica Andriesen, Associate Director of Data OperationsLisa Bunts, Data Operations Project ManagerLauren Young, Lab Data ManagerNada Aboulhosn, Research Project ManagerKate Ostbye, Sr. Manager, ProgrammingJulie Stofel, Manager, Clinical ProgrammingCraig Chin, Prin. Clinical ProgrammerBrad Fischer, Sr. Clinical ProgrammerAbby Isaacs, Statistical Research AssociateAlex Luedtke, Study StatisticianMarco Carone, Study Statistician
26. HPX3002/HVTN 706 AcknowledgementsNational Institute of Allergy and Infectious DiseasesU.S. Army Medical Research and Development Command
27. Acknowledgements Janssen COMPOUND DEVELOPMENT TEAMIedo BeeksmaAntoine El Khoury Ad KnaapenSteven NijsValerie Oriol-MathieuMaria Grazia PauLorenz SchepplerDaniel StiehFrank TomakaJohn TrottFrank WegmannMo Weijtens...and their teamsSenior management Jerry SadoffStefan ThoelenMacaya DouoguihJenny HendriksHanneke SchuitemakerJohan van HoofMathai MammenPaul StoffelsAll the investigators, their staffs and study participants, external consultants and funders of the clinical development programDAIDS, NIAIDCarl DieffenbachJulia HutterMary MarovichTina TongCommunities and advocates for their valuable input