MOSAICO: A Study of Heterologous Vaccine Regimen of Adenovirus Serotype 26 Mosaic4 Human Immunodeficiency Virus(Ad26.Mos4.HIV), 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

• Sponsor: Janssen Vaccines & Prevention B.V. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03964415
• Collaborator: (none)
• Enrollment: 3,900
• Locations: 53
• Arms: 2
• Anticipated Duration (Months): 52.4
• Patients Per Site: 73.6
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the vaccine efficacy (VE) of a heterologous vaccine regimen utilizing Ad26.Mos4.HIV and aluminum phosphate-adjuvanted Clade C gp140 and Mosaic gp140 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: Ad26.Mos4.HIV; Biological: Clade C and Mosaic gp140 HIV bivalent vaccine; Biological: Placebo	Phase 3

Detailed Description

Human immunodeficiency virus type 1 (HIV-1) is a retrovirus that, if left untreated, can progress to acquired immunodeficiency syndrome (AIDS), a condition in which the immune system is severely compromised, leading to life-threatening conditions. Ad26.Mos4.HIV is a tetravalent vaccine composed of Ad26.Mos1.Gag-Pol, Ad26.Mos2.Gag-Pol, Ad26.Mos1.Env, and Ad26.Mos2S.Env. Clade C and Mosaic gp140 HIV bivalent vaccine contains: Clade C gp140, HIV-1 Env gp140 of Clade C, Mosaic gp140, HIV-1 Env gp140, and aluminum phosphate adjuvant. Evidences showed that a combination of vaccination with Ad26.Mos.HIV followed by Ad26.Mos.HIV together with Clade C gp140 protein in aluminum phosphate adjuvant led to highest level of protection observed so far with this vaccine concept. Study comprises of a screening period of 45 days, a 12-month vaccination period and a follow-up period of at least 18 months after fourth vaccination (until Month 30) in participants who remain HIV-1 negative or up to 6 months after diagnosis of HIV-1 infection in participants who become HIV-1 infected. Participants who completed their Month 30 visit will be followed for HIV infection, medically-attended adverse event (MAAEs) and serious adverse events until the end of study (Month 30). Primary analysis of vaccine efficacy will evaluate the number of HIV-1 infections in the vaccine group compared to number of HIV-1 infections in the placebo group between Month 7 and Month X (with 24<=X<=30) in per-protocol population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3900 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: Oct 31, 2019
• Anticipated Primary Completion Date: Mar 13, 2024
• Anticipated Study Completion Date: Mar 13, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group1:Ad26.Mos4.HIV,Clade C and Mosaic gp140 bivalent vaccine Participants will receive adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) via intramuscular (IM) injection into the deltoid muscle at months 0 (Day 1) and 3 (preferably the deltoid of the non-dominant upper arm) and, Ad26.Mos4.HIV together with Clade C and Mosaic gp140 HIV bivalent vaccine IM into the deltoid muscle at Months 6 and 12 (different deltoid for each injection).	Biological: Ad26.Mos4.HIV; Participants will receive Ad26.Mos4.HIV via IM injection into the deltoid muscle at months 0 (Day 1), 3, 6 and 12.; Biological: Clade C and Mosaic gp140 HIV bivalent vaccine; Participants will receive Clade C and Mosaic gp140 HIV bivalent vaccine as IM injection into the deltoid muscle at Months 6 and 12.
Placebo Comparator: Group 2: Placebo Participants will receive placebo into the deltoid muscle on Months 0 (Day 1), 3 (1 injection), 6 and 12 (2 injections).	Biological: Placebo; Participants will receive matching placebo.

Outcome Measures

Primary Outcome Measures

1. Vaccine Efficacy (VE) as Derived From Confirmed HIV-1 Infections Diagnosed Between the Month 7 and Month X (with 24 Less Than or Equal to [<=] X <= 30) Visits [From Month 7 up to Month 30]

   Vaccine efficacy is defined as 1-cumulative incidence ratio (vaccine versus placebo) between Month 7 and Month X after first vaccination and is estimated by the transformation of the Nelson-Aalen estimator for the cumulative hazard function after enrollment in the per-protocol (PP) population. Here, month X will be between month 24 and month 30.

Secondary Outcome Measures

1. Number of Participants with Solicited Local and Systemic Adverse Events (AEs) [7 days after each vaccination on Months 0, 3, 6, and 12]

   Number of participants with local solicited adverse events will be evaluated. An adverse event is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product and does not necessarily have a causal relationship with the intervention, therefore it can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. Solicited local AEs include assessment of pain/tenderness, erythema and swelling. Solicited systemic AEs: fatigue, headache, nausea, myalgia, chills, arthralgia, and vomiting will be assessed.

2. Number of Participants with Unsolicited Adverse Events [28 days after each vaccination on Months 0, 3, 6, and 12]

   Number of Participants with unsolicited AEs will be evaluated. Unsolicited adverse events are all adverse events for which the participant is specifically not questioned in the participant diary.

3. Number of Participants with Adverse Events of Special Interest (AESIs) [Up to 6 months after the last vaccination (Month 18)]

   Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI.

4. Number of Participants with Medically-attended adverse events (MAAEs) [Up to 43 Months (participants will be followed until the last participant reaches Month 30)]

   Number of participants with MAAEs will be evaluated. MAAEs are defined as adverse events with medically attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.

5. Number of Participants with Serious Adverse Events (SAEs) [Up to 43 Months (participants will be followed until the last participant reaches Month 30)]

   Number of participants with SAE will be evaluated. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.

6. Number of Participants who Discontinue from the Study or Vaccination due to Adverse Events [Up to 43 Months (participants will be followed until the last participant reaches Month 30)]

   Number of participants who discontinue from the study or vaccination due to AEs will be evaluated. Participants will be withdrawn from study vaccine administration due to unblinding due to safety reasons, Pregnancy, Confirmed HIV-1 infection, Any related adverse event, Worsening of health status or intercurrent illnesses that in the opinion of the investigator, Required discontinuation from study vaccine, Anaphylactic reaction following vaccination, Serious adverse event or other potentially life-threatening (Grade 4) event that is determined to be related to study vaccine, Chronic or recurrent use of systemic immunomodulators/suppressants, example, cancer chemotherapeutic agents (after discussion with the sponsor), Use of HIV-related monoclonal antibodies (mAbs).

7. Vaccine Efficacy as Derived From Confirmed HIV-1 Infections Diagnosed at VE (0-X months) per Modified Intent-to-Treat (mITT) Population [Month 0 (Day 1) up to Month 30]

   Vaccine efficacy is defined as 1-cumulative incidence ratio (vaccine versus placebo) between Month 0 and Month X after first vaccination and is estimated by the transformation of the Nelson-Aalen estimator for the cumulative hazard function per mITT populations. Here, month X will be between month 24 and month 30.

8. Vaccine Efficacy as Derived From Confirmed HIV-1 Infections Diagnosed at VE (13-X months) per mITT Population [Month 13 up to Month 30]

   Vaccine efficacy is defined as 1-cumulative incidence ratio (vaccine versus placebo) between Month 13 and Month X after first vaccination and is estimated by the transformation of the Nelson-Aalen estimator for the cumulative hazard function per mITT populations. Here, month X will be between month 24 and month 30.

9. Frequency of HIV-1 Env-Specific Humoral Immune Responses as Determined by Clade C gp140 and Mos1 gp140 Specific ELISA [Month 0 (Day 1) up to Month 30]

   Frequency of HIV-1 Env-specific humoral immune responses in PP population will be determined by Clade C gp140 and Mos1 gp140 specific enzyme-linked immunosorbent assay (ELISA).

10. Frequency of HIV-1 Env-Specific Cellular Immune Responses as Determined by Clinical Potential T Cell Epitopes Envelope Peptide Enzyme-Linked Immunospot [Month 0 (Day 1) up to Month 30]

    Frequency of HIV-1 Env-specific cellular immune responses in PP population will be determined by clinical potential T cell epitopes (cPTE) envelope (Env) peptide enzyme-linked immunospot (ELISpot).

11. Magnitude of HIV-1 Env-Specific Humoral Immune Responses as Determined by Clade C gp140 and Mos1 gp140 specific ELISA [Month 0 (Day 1) up to Month 30]

    Magnitude of HIV-1 Env-specific humoral immune responses in PP population will be determined by Clade C gp140 and Mos1 gp140 specific ELISA.

12. Magnitude of HIV-1 Env-Specific Cellular Immune Responses as Determined by cPTE Env peptide ELISpot [Month 0 (Day 1) up to Month 30]

    Magnitude of HIV-1 Env-specific cellular immune responses in PP population will be determined by cPTE Env peptide ELISpot.

13. Vaccine Efficacy Assessed by Demographic Characteristics [Month 0 (Day 1) up to Month 30]

    The vaccine efficacy assessed by demographic characteristics diagnosed by HIV-1 infection will be reported.

14. Number of Participants who are Ad26 Seropositive [Month 0 (Day 1) up to Month 30]

    Number of participants who are Ad26 seropositive will be assessed by vector neutralization assay.

15. Antibody Titers for Ad26 as Determined by Vector Neutralization Assay [Month 0 (Day 1) up to Month 30]

    Antibody titers will be determined by vector neutralization assay.

16. Sexual Risk Behavior as Assessed by Sexual Activity Questionnaire [Month 0 (Day 1) up to Month 30]

    Sexual risk behavior collected through sexual activity questionnaire (composed with 36 questions) in which participants will be asked about specific sexual activities.

17. Pre-Exposure Prophylaxis (PrEP) Uptake as Measured by Self Report Questionnaire [Month 0 (Day 1), 3, 6, 9, 12, 15, 18, 21, 24, 27, 30 and every 3 months post month 30 (up to 48 months)]

    For HIV-negative participants, participants will be asked whether they use HIV PrEP as part of a self-report questionnaire (composed of 5 questions).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Individual is either cis-gender man having sex with cis-gender men and/or transgender individuals or transgender woman having sex with cis-gender men and/or transgender individuals or transgender man having sex with cis-gender men and/or transgender women or gender non-conforming individual having receptive or insertive anal and/or vaginal condom-less intercourse and who is considered by the site staff to be at increased risk for HIV-1 infection. The potential participants must in the last 6 months have had any condom-less receptive anal or vaginal sex (not included is condom-less 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 or any other drug and/or substance which in the local context may be associated with increased HIV transmission (example, cocaine, amphetamine) or 5 or more sex partners

• Potential participant has a negative test result for HIV-1 and HIV-2 infection less than or equal to (<=) 28 days prior to first vaccination

• Potential participant must be healthy based on medical history, physical examination, and vital sign measurement performed at screening

• Contraceptive use by participants assigned female at birth and who have not had sexual reassignment surgery should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies

• All participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening and have a negative urine beta-hCG pregnancy test immediately prior to each study vaccine administration

Exclusion Criteria:

• Potential participants choosing to use PrEP. However, once participants are enrolled and received their first vaccination, and they change their mind regarding PrEP usage, they will be allowed to take PrEP according to the site PrEP plan and will continue to receive further vaccinations. The use of long acting PrEP is disallowed from 24 months prior to Day 1

• Potential participant is a recipient of a HIV-vaccine candidate at any time, or a recipient of other experimental vaccine(s) within the last 12 months prior to Day 1. For participants who received an experimental vaccine (except HIV vaccine) more than 12 months prior to Day 1, documentation of the identity of the experimental vaccine must be provided to the HPX3002/HVTN 706 safety review team, who will determine eligibility on a case by-case basis. Exceptions: participants can be included if the vaccine received (except HIV vaccine) was subsequently licensed or authorized for emergency use (example, Emergency Use Authorization (EUA), Emergency Use Listing (EUL), or similar program). Participants with proof of having received only placebo can also be included. Participants who are currently still in an interventional study of such a licensed/emergency use-authorized vaccine are to be excluded from the current study

• Potential participant has received an HIV-related mAb, whether licensed or investigational, within the last 12 months prior to Day 1. For participants who received an HIV-related mAb more than 12 months prior to Day 1, documentation of the identity of the mAb must be provided to the HPX3002/HVTN 706 safety review team, who will determine eligibility on a case-by-case basis.

• Potential participant has known allergy or history of anaphylaxis or other serious adverse reactions to vaccines

• Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study vaccination

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35222
2	Bridge HIV	San Francisco	California	United States	94102
3	Whitman Walker Health	Washington	District of Columbia	United States	20816
4	University of Miami	Miami	Florida	United States	33136
5	Orlando Immunology Center	Orlando	Florida	United States	32803
6	Emory University Rollins School of Public Health - Ponce De Leon CRS	Atlanta	Georgia	United States	30322
7	The Hope Clinic at Emory University	Decatur	Georgia	United States	30030
8	University Of Illinois	Chicago	Illinois	United States	60612
9	New Orleans Adolescent Trials Unit CRS	New Orleans	Louisiana	United States	70112
10	Dana-Farber/Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
11	Fenway Health	Boston	Massachusetts	United States	02215
12	Rutgers, The State University of New Jersey - The University Hospital/ACTG Network	Newark	New Jersey	United States	07103
13	Harlem Prevention Center CRS	New York	New York	United States	10027
14	Columbia University Medical Center	New York	New York	United States	10032
15	New York Blood Center	New York	New York	United States	10065
16	Strong Memorial Infectious Disease	Rochester	New York	United States	14642
17	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
18	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212
19	Gordon E. Crofoot MD	Houston	Texas	United States	77098
20	Seattle Vaccine Trials Unit	Seattle	Washington	United States	98104
21	Helios Salud Sa	Buenos Aires		Argentina	C1141ACG
22	Fundacion Huesped	Ciudad Autonoma De Buenos Aire		Argentina	C1202ABB
23	Hospital J. M. Ramos Mejía	Ciudad de Buenos Aires		Argentina	C1221Adc
24	Instituto Caici Srl.	Rosario		Argentina	S2000PBJ
25	Hospital de Clinicas da Universidade Federal De Minas Geraisnas Gerais	Belo Horizonte		Brazil	30130-100
26	Centro Medico Sao Francisco	Curitiba		Brazil	80810-050
27	Fundação De Medicina Tropical Doutor Heitor Vieira Dourado	Manaus		Brazil	69040-000
28	Instituto Nacional de Infectologia Evandro Chagas (INI) - FIOCRUZ	Rio De Janeiro		Brazil	21040-360
29	Hospital Geral de Nova Iguacu - HGNI DST/AIDS	Rio De Janeiro		Brazil	26030-380
30	Instituto de infectologia Emilio Ribas	Sao Paulo		Brazil	01246-900
31	Centro de Referencia E Treinamento Dst/Aids	Sao Paulo		Brazil	02141-000
32	Faculdade De Medicina Da Universidade De São Paulo	São Paulo		Brazil	01246-903
33	Ospedale San Raffaele	Milano		Italy	20127
34	Azienda Ospedaliero-Universitaria Policlinico di Modena	Modena		Italy	41124
35	Istituto nazionale malattie infettive 'L. Spallanzani'	Roma		Italy	00149
36	Hospital Civil Fray Antonio Alcalde	Guadalajara		Mexico	44280
37	Unidad de Atención Medica e Investigacion en Salud (UNAMIS)	Merida		Mexico	97000
38	Inst. Nal. de Ciencias Med. Y Nutricion Salvador Zubiran	Mexico City		Mexico	14000
39	Centro de Investigaciones Tecnologicas, Biomedica y medio ambientales (CITBM)	Callao		Peru	07066
40	Asociacion Civil Selva Amazonica (ACSA)	Iquitos		Peru	16001
41	Asociacion Civil Impacta Salud y Educacion - Barranco	Lima - Barranco		Peru	Barranco 15063
42	Asociacion Civil Impacta Salud y Educacion- San Miguel CRS	Lima - San Miguel		Peru	15088
43	Asociacion Civil Via Libre	Lima		Peru	15001
44	Neutrum Lekarze M.Hlebowicz i Partnerzy spolka partnerska	Gdansk		Poland	80-462
45	Wroclawskie Centrum Zdrowia SPZOZ, Poradnia Profilaktyczno-Lecznicza	Wroclaw		Poland	50-136
46	Clinical Research Puerto Rico Inc	San Juan		Puerto Rico	00909
47	University of Puerto Rico	San Juan		Puerto Rico	00936-5067
48	Hosp. Univ. Germans Trias I Pujol	Badalona		Spain	08916
49	Hosp. Univ. Vall D Hebron	Barcelona		Spain	08001
50	Hosp. Reina Sofia	Córdoba		Spain	14004
51	Hosp. Univ. Fund. Jimenez Diaz	Madrid		Spain	28015
52	Hosp. Clinico San Carlos	Madrid		Spain	28040
53	Hosp. Gral. Univ. Valencia	Valencia		Spain	46014

Sponsors and Collaborators

• Janssen Vaccines & Prevention B.V.

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial, Janssen Vaccines & Prevention B.V.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Vaccines & Prevention B.V.
• ClinicalTrials.gov Identifier: NCT03964415
• Other Study ID Numbers: CR108604; 2018-003666-13; VAC89220HPX3002; HVTN 706
• First Posted: May 28, 2019
• Last Update Posted: Aug 3, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections

Study Results

No Results Posted as of Aug 3, 2022