1. HIV Vaccine efficacy studies and the MOSAICO clinical trial
Sabrina Spinosa Guzman Janssen Protocol Chair
HVTN satellite
21st July 2019

2. Disclosure I have the following conflicts of interest to declare:
I am an employee of Janssen Vaccines & Prevention B.V., a pharmaceutical company of Johnson & Johnson
I hold equity shares in Johnson & Johnson

3. Towards a global HIV vaccine

4. Clade diversity Transmission mode Use of PrEP
Considerations for efficacy
evaluation

5. Clinical development plan
NHP #13-19
Ph2a APPROACH N=393
FIH Ad26.Mos.HIV and heterologous regimens
F. Tomaka: Tue, 23 Jul
Casa Montejo 1
Session: 14:30-16:00
Ph2a TRAVERSE N=198
Ad26.Mos4.HIV vs Ad26.Mos.HIV
Ph2b IMBOKODO N=2,637
Ph2a ASCENT N=150
Boost with Clade C+Mos gp140 vs Clade C alone
D. Stieh: Tue, 23 Jul
Palacio de Valparaíso 2
Session: 16:30-18:00
Ph3 MOSAICO N=3,800
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2014
2015
2016
2017
2018
2019
2020
2021
2022

6. IMBOKODO MOSAICO Ph2b Ph3 Southern Africa Americas, Europe
Predominantly Clade C
Predominantly Clade B
Heterosexual Women
MSM + TG
Intra-vaginal transmission
Intra-rectal transmission
Limited PrEP use
Increased PrEP use

7. IMBOKODO
HPX2008/HVTN705
A phase 2b multicenter, randomized, parallel group, placebo-controlled, double-blind clinical trial.

8. IMBOKODO - Study design
N=2,600 women, 1:1 randomization, +/- 1.5 year recruitment
Primary analysis
Study completion
Group N
Vacc 1
Mo 0
Vacc 2
Mo 3
Vacc 3 Mo 6
Vacc 4 Mo 12
Follow up
Month 24
Follow up
Month 36 1
1,300
Ad26.Mos4.HIV
Ad26.Mos4.HIV,
CladeC gp140 2
Placebo

9. Primary Objectives and Endpoints
Primary Objectives To 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 Endpoints
Vaccine 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. Clinical development plan
NHP #13-19
Ph2a APPROACH N=393
FIH Ad26.Mos.HIV and heterologous regimens
Ph2a TRAVERSE N=198
Ad26.Mos4.HIV vs Ad26.Mos.HIV
Ph2b IMBOKODO N=2,600
Ph2a ASCENT N=150
Boost with Clade C+Mos gp140 vs Clade C alone
Ph3 MOSAICO N=3,800
2014
2015
2016
2017
2018
2019
2020
2021
2022
2023
2014
2015
2016
2017
2018
2019
2020
2021
2022

11. MOSAICO
HPX3002/HVTN706
A 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 design
3,800 participants; 1:1 randomization (stratified by site)
Group N
Vacc 1
Mo 0
Vacc 2
Mo 3
Vacc 3 Mo 6
Vacc 4 Mo 12
Follow‑up
HIV-1 negative: ≥24 m after 3rd vaccination
HIV-1 positive: m after diagnosis
Follow up
Month 24-30
Primary analysis 1
1,900
Ad26.Mos4.HIV
Ad26.Mos4.HIV,
CladeC + Mosaic gp140 2
Placebo

13. Primary Objective and Endpoint
Primary Objective To 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 Endpoint
Confirmed HIV-1 infections diagnosed between Month 7 and Month x (with 24≤x≤30 months) visits in the per- protocol (PP) population.

14. Secondary Objectives
Secondary Objectives To 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 criteria
HIV-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), OR
Rectal or urethral gonorrhea or chlamydia or incident syphilis, OR
Any stimulant use (eg, cocaine, amphetamine), OR
5 or more sex partners 
Potential participant is negative for HIV-1 and HIV-2 infection <28 days prior to first vaccination.

16. Main exclusion criteria
Potential participant shares needles during injection of drugs or any other substance.
Potential participant choosing to use PrEP
Note: 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 study
All participants will be offered comprehensive prevention methods:
Risk reduction counseling
Condom and lubricant provision
Pre-Exposure prophylaxis counseling, referral, and linkage
Post Exposure prophylaxis counseling referral, and linkage
STI screening, access to treatment and referral
The trial will allow some comparison of the Vaccine + Standard Prevention package vs. Standard Prevention package alone

18. Global site distribution
Argentina: 4
USA: 24
Mexico: 3
Peru: 5
Brazil: 9
Poland: 3
Spain: 6
Italy: 3
Europe
Americas

19. Overview of Study Evaluations
0 months 3 6 7 9 12 13
15-30
FU After 30
Vaccination
HIV test
Q3mo
Humoral
Q6mo
Cellular
Chlamydia/
Gonorrhea
Q6mo
Syphilis
Safety
Solicited
Unsolicited
Continuously

20. Efficacy Evaluations
An 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 Outcomes
Sexual Activity Questionnaire Assess 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 individuals
Participants 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 events
Event
Confirm 3 6
Exit
HIV test
HIV VL
CD4
ART
Social Impact
Counsel
Humoral/
Cellular

23. IMBOKODO MOSAICO Ph2b Ph3 Fully enrolled Q2 2019 Start Q3 2019
Southern Africa
Americas, Europe
Predominantly Clade C
Predominantly Clade B
Heterosexual Women
MSM + TG
Intra-vaginal transmission
Intra-rectal transmission
Limited PrEP use
Increased PrEP use
Fully enrolled Q2 2019
Start Q3 2019

24. HPX3002/HVTN 706 Protocol Team Acknowledgements
Janssen Team
Sabrina Spinosa Guzman, Protocol Leadership Chair
Ludo Lavreys, Study Responsible Physician
Chris McShane, GCDO Clinical Program Leader
Vicky Cárdenas, Study Responsible Scientist
Karen Buleza, GCDO Clinical Trial Leader
Frank Tomaka, Franchise Clinical Leader
Johan De Decker, Senior Clinical Trial Manager
Maria Grazia Pau, Compound Development Team Leader
Cornelia Linthicum, Senior Clinical Trial Manager
Carla Truyers, Study Statistician
Eveline Hoste, Associate Director Reg Medical Writing
Steven Nijs, Clinical Team Statistical Lead
Anick Vandingenen, Associate Dir. Reg Medical Writing
Daniel Stieh, Biomarkers Lead
Corina Ramers-Verhoeven, Global Communication Leader, Vaccines R&D
Zelda Euler, Senior Scientist
Wolf Ribbens, Senior Associate Scientist
Raphaele Roten, Medical Safety Officer
Lorenz Scheppler, Global Regulatory Affairs
Olive Yuan, Associate Director Data Management
Caroline Hodin, Global Data Manager Specialist
Wouter Vandermeiren, Senior Global Data Manager

25. HPX3002/HVTN 706 Protocol Team Acknowledgements
HVTN Team Larry Corey, Principal Investigator Jim Kublin, Principal Staff Scientist Susan Buchbinder, HVTN Chair Philipp Mann, Protocol Team Leader Megan Jones, Clinical Safety Specialist Robert De La Grecca, Regional Medical Liaison India Tindale, Clinical Trials Manager Niles Eaton, Director of Site Operations Laurie Rinn, Regulatory Associate Mariel Franklin, Regulatory Project Manager Stephaun Wallace, Sen Community Engagement Project Manager Aziel Gangerdine, Director of Communication Steven Wakefield, Director of External Relations DAIDS Julia Hutter, Medical Officer Lab John Hural, Associate Director of Laboratory Operations Mike Stirewalt, Quality Assurance Program Manager Katheryn Dougherty, Quality Assurance Associate Jennifer Hanke, Protocol Operations Coordinator Lisa Sanders, Protocol Operations Coordinator SCHARP Jessica Andriesen, Associate Director of Data Operations Lisa Bunts, Data Operations Project Manager Lauren Young, Lab Data Manager Nada Aboulhosn, Research Project Manager Kate Ostbye, Sr. Manager, Programming Julie Stofel, Manager, Clinical Programming Craig Chin, Prin. Clinical Programmer Brad Fischer, Sr. Clinical Programmer Abby Isaacs, Statistical Research Associate Alex Luedtke, Study Statistician Marco Carone, Study Statistician

26. HPX3002/HVTN 706 Acknowledgements
National Institute of Allergy and Infectious Diseases
U.S. Army Medical Research
and Development Command

27. Acknowledgements Communities and advocates for their valuable input
Janssen COMPOUND DEVELOPMENT TEAM Iedo Beeksma
Antoine El Khoury
Ad Knaapen
Steven Nijs
Valerie Oriol-Mathieu
Maria Grazia Pau
Lorenz Scheppler
Daniel Stieh
Frank Tomaka
John Trott
Frank Wegmann
Mo Weijtens
...and their teams
DAIDS, NIAID Carl Dieffenbach
Julia Hutter
Mary Marovich
Tina Tong
Senior management
Jerry Sadoff
Stefan Thoelen
Macaya Douoguih
Jenny Hendriks
Hanneke Schuitemaker
Johan van Hoof
Mathai Mammen
Paul Stoffels
Communities and advocates for their valuable input
All the investigators, their staffs and study participants, external consultants and funders of the clinical development program