Trial Outcomes & Findings for A Study to Assess the Efficacy of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa (NCT NCT03060629)

Last Updated: 2023-04-18

Results Overview

Number of participants with HIV-1 infection diagnosed between Month 7 to Month 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2636 participants

Primary outcome timeframe

Month 7 up to Month 24

Results posted on

2023-04-18

Participant Flow

For Participant Flow below, data were summarized based on assigned treatment.

Participant milestones

Participant milestones
Measure	Group 1: Ad26.Mos.HIV Vaccine Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Overall Study STARTED	1313	1323
Overall Study COMPLETED	78	88
Overall Study NOT COMPLETED	1235	1235

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: Ad26.Mos.HIV Vaccine Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Overall Study Death	4	5
Overall Study Withdrawal by Subject	50	35
Overall Study Unable to Adhere to Visit Schedule	21	23
Overall Study Participant Relocate	15	15
Overall Study Unable to Contact Participant	34	23
Overall Study Investigator Decision	7	7
Overall Study Study Terminated by Sponsor	1100	1123
Overall Study Other	4	4

Baseline Characteristics

A Study to Assess the Efficacy of a Heterologous Prime/Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1313 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1323 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.	Total n=2636 Participants Total of all reporting groups
Age, Continuous	22 years n=5 Participants	23 years n=7 Participants	23 years n=5 Participants
Sex: Female, Male Female	1313 Participants n=5 Participants	1323 Participants n=7 Participants	2636 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1313 Participants n=5 Participants	1323 Participants n=7 Participants	2636 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black	1302 Participants n=5 Participants	1317 Participants n=7 Participants	2619 Participants n=5 Participants
Race/Ethnicity, Customized Colored/Mixed	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Indian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment MALAWI	78 Participants n=5 Participants	79 Participants n=7 Participants	157 Participants n=5 Participants
Region of Enrollment MOZAMBIQUE	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Region of Enrollment SOUTH AFRICA	882 Participants n=5 Participants	892 Participants n=7 Participants	1774 Participants n=5 Participants
Region of Enrollment ZAMBIA	164 Participants n=5 Participants	165 Participants n=7 Participants	329 Participants n=5 Participants
Region of Enrollment ZIMBABWE	166 Participants n=5 Participants	165 Participants n=7 Participants	331 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 7 up to Month 24

Population: Per protocol (PP) population set included participants from the full analysis set (FAS; all randomized participants who received at least one study vaccine administration) who were HIV-1 uninfected 4 weeks after the third vaccination visit, who received all planned vaccinations at the first 3 vaccination visits within the respective visit windows and had no other major protocol deviations that were judged to possibly impact the efficacy of the vaccine.

Number of participants with HIV-1 infection diagnosed between Month 7 to Month 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1080 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1108 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Number of Participants With Human Immuno Deficiency Virus-1 (HIV-1) Infection Diagnosed Between Month 7 to Month 24 Post Enrollment	54 Participants	65 Participants

PRIMARY outcome

Timeframe: Up to 7 days after first vaccination on Day 0 (Day 7)

Population: FAS included all randomized participants who received at least 1 vaccine administration. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure. The safety analyses were performed based on the actual treatment that the participants received after the first vaccination. Hence, one participant from Group 2 was analyzed in Group 1 for this outcome measure.

Percentage of participants with local reactogenicity signs and symptoms after first vaccination were reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1316 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1320 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After First Vaccination	34.2 Percentage of participants	9.4 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after second vaccination on Day 84 (Day 91)

Percentage of participants with local reactogenicity signs and symptoms after second vaccination was reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1190 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1215 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After Second Vaccination	20.0 Percentage of participants	8.1 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after third vaccination on Day 168 (Up to Day 175)

Percentage of participants with local reactogenicity signs and symptoms after third vaccination was reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1160 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1188 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After Third Vaccination	25.2 Percentage of participants	8.9 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)

Percentage of participants with local reactogenicity signs and symptoms after fourth vaccination was reported. Local reactogenicity events (solicited local adverse events) were defined as events at the injection site. Local reactogenicity signs and symptoms included pain and/or tenderness proximal to the injection site.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1099 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1111 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Local Reactogenicity Signs and Symptoms After Fourth Vaccination	25.7 Percentage of participants	8.6 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after first vaccination on Day 0 (Day 7)

Percentage of participants with systematic reactogenicity signs and symptoms after first vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1316 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1320 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After First Vaccination	52.9 Percentage of participants	40.9 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after second vaccination on Day 84 (Day 91)

Percentage of participants with systematic reactogenicity signs and symptoms after second vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1190 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1215 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Second Vaccination	33.2 Percentage of participants	28.6 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after third vaccination on Day 168 (Up to Day 175)

Percentage of participants with systematic reactogenicity signs and symptoms after third vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1160 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1188 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Third Vaccination	31.5 Percentage of participants	26.8 Percentage of participants

PRIMARY outcome

Timeframe: Up to 7 days after fourth vaccination on Day 364 (Up to Day 371)

Percentage of participants with systematic reactogenicity signs and symptoms after fourth vaccination was reported. Systemic reactogenicity events (solicited systemic adverse events) defined as events occurred in a predefined post-vaccination period for which the subject was specifically questioned. Systemic reactogenicity signs and symptoms included increased body temperature, malaise and/or fatigue, myalgia, headache, chills, arthralgia, nausea, and vomiting.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1099 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1111 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Systematic Reactogenicity Signs and Symptoms After Fourth Vaccination	29.4 Percentage of participants	23.6 Percentage of participants

PRIMARY outcome

Timeframe: 30 days after first vaccination on Day 0 (Up to Day 30)

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1316 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1320 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Unsolicited Adverse Events (AEs) for 30 Days After First Vaccination	16.6 Percentage of participants	14.8 Percentage of participants

PRIMARY outcome

Timeframe: 30 days after second vaccination on Day 84 (Up to Day 114)

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1190 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1215 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Unsolicited AEs for 30 Days After Second Vaccination	17.1 Percentage of participants	15.1 Percentage of participants

PRIMARY outcome

Timeframe: 30 days after third vaccination on Day 168 (Up to Day 198)

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1160 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1188 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Unsolicited AEs for 30 Days After Third Vaccination	39.8 Percentage of participants	40.3 Percentage of participants

PRIMARY outcome

Timeframe: 30 days after fourth vaccination on Day 364 (Up to Day 394)

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1099 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1111 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Unsolicited AEs for 30 Days After Fourth Vaccination	63.5 Percentage of participants	62.5 Percentage of participants

PRIMARY outcome

Timeframe: Up to Month 36 (up to end of the study)

Population: FAS included all randomized participants who received at least 1 vaccine administration. The safety analyses were performed based on the actual treatment that the participants received.

An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with the study treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1317 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1319 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Serious Adverse Events (SAEs)	3.7 Percentage of participants	2.8 Percentage of participants

PRIMARY outcome

Timeframe: Up to Month 36 (up to end of the study)

Population: FAS included all randomized participants who received at least 1 vaccine administration. The safety analyses were performed based on the actual treatment that the participants received.

Percentage of participants with AESIs was reported. Immune-mediated diseases were considered as AESIs in this study.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1317 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1319 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With Adverse Events of Special Interest (AESIs)	0.2 Percentage of participants	0.2 Percentage of participants

PRIMARY outcome

Timeframe: Up to Month 36 (up to end of the study)

Population: FAS included all randomized participants who received at least 1 vaccine administration. The safety analyses were performed based on the actual treatment that the participants received.

Percentage of participants with AEs leading to early participant withdrawal or early discontinuation of study product were reported. An AE is any untoward medical occurrence in a clinical investigation participant administered a study product and which does not necessarily have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1317 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1319 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Percentage of Participants With AEs Leading to Early Participant Withdrawal or Early Discontinuation of Study Product	0.2 Percentage of participants	0.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: Modified Intent-to-Treat (MITT) analysis set included participants in the FAS who were HIV-1 uninfected on the date of first vaccination.

Number of participants with HIV-1 infection diagnosed from enrollment (baseline) through month 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1311 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1319 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Number of Participants With HIV-1 Infection Diagnosed From Enrollment (Baseline) Through Month 24 Post Enrollment	91 Participants	102 Participants

SECONDARY outcome

Timeframe: Baseline up to Month 36 (End of study)

Population: MITT analysis set included participants in the FAS who were HIV-1 uninfected on the date of first vaccination.

Number of participants with HIV-1 infection diagnosed from enrollment (baseline) through Month 36 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1311 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1319 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Number of Participants With HIV-1 Infection Diagnosed From Enrollment (Baseline) Through Month 36 (End of Study) Post Enrollment	115 Participants	127 Participants

SECONDARY outcome

Timeframe: Month 13 up to Month 24

Population: Full immunization set (FIS) included participants in the FAS who were HIV-1 uninfected 4 week after the fourth vaccination visit and who received all planned vaccinations within the respective visit windows.

Number of participants with HIV-1 infection diagnosed from Month 13 through Month 24 post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=981 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=995 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Number of Participants With HIV-1 Infection Diagnosed From Month 13 Through Month 24 Post Enrollment	32 Participants	35 Participants

SECONDARY outcome

Timeframe: Month 13 up to Month 36 (End of study)

Population: FIS included participants in the FAS who were HIV-1 uninfected 4 week after the fourth vaccination visit and who received all planned vaccinations within the respective visit windows.

Number of participants with HIV-1 infection diagnosed from Month 13 through Month 36 (end of study) post enrollment was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=981 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=995 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Number of Participants With HIV-1 Infection Diagnosed From Month 13 Through Month 36 (End of Study) Post Enrollment	53 Participants	58 Participants

SECONDARY outcome

Timeframe: Months 0, 7, 13 and 24

Population: FIS included participants in the FAS who were HIV-1 uninfected 4 weeks after the fourth vaccination visit and who received all planned vaccinations within the respective visit windows. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

A weighted geometric mean of the binding antibody responses to HIV envelope (ENV) gp140 Clade C 97ZA protein analyzed by ELISA was reported.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=50 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=10 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Geometric Mean of Binding Antibody Responses to HIV Envelop (ENV) Clade (gp140) C (ZA) Analyzed by Enzyme-linked Immunosorbent Assay (ELISA) Month 0	53 ELISA Units per milliliter (EU/mL) Interval 45.0 to 63.0	43 ELISA Units per milliliter (EU/mL) Interval 37.0 to 49.0
Geometric Mean of Binding Antibody Responses to HIV Envelop (ENV) Clade (gp140) C (ZA) Analyzed by Enzyme-linked Immunosorbent Assay (ELISA) Month 7	38834 ELISA Units per milliliter (EU/mL) Interval 26484.0 to 56942.0	43 ELISA Units per milliliter (EU/mL) Interval 37.0 to 49.0
Geometric Mean of Binding Antibody Responses to HIV Envelop (ENV) Clade (gp140) C (ZA) Analyzed by Enzyme-linked Immunosorbent Assay (ELISA) Month 13	66147 ELISA Units per milliliter (EU/mL) Interval 50523.0 to 86602.0	62 ELISA Units per milliliter (EU/mL) Interval 36.0 to 109.0
Geometric Mean of Binding Antibody Responses to HIV Envelop (ENV) Clade (gp140) C (ZA) Analyzed by Enzyme-linked Immunosorbent Assay (ELISA) Month 24	5920 ELISA Units per milliliter (EU/mL) Interval 4559.0 to 7688.0	49 ELISA Units per milliliter (EU/mL) Interval 33.0 to 72.0

SECONDARY outcome

Timeframe: Months 0, 7, 13 and 24

Population: FIS included participants who were HIV-1 uninfected 4 week after the fourth vaccination visit and who received all planned vaccinations within the respective visit windows. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure and 'n' (number analyzed) signifies number of participants who were analyzed at specified timepoints.

Geometric mean of IFN-gamma T-cells responses analyzed by ELISpot were reported. A weighted geometric mean of the number of spot-forming cells (SFC) per million peripheral blood mononuclear cells (PBMCs) producing Interferon-gamma upon stimulation with potential T-cell epitope (PTE) ENV peptide pools analyzed by ELISpot was reported. Reported responses are the sum of the number of SFCs/10\^6 PBMCS for PTE Env1, Env2 and Env3 sub-pools.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=50 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=10 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Geometric Mean of Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) Month 0	33.5 SFC/million PBMCs Interval 29.7 to 33.7	30.0 SFC/million PBMCs Interval 30.0 to 30.0
Geometric Mean of Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) Month 7	241.2 SFC/million PBMCs Interval 168.0 to 346.2	33.9 SFC/million PBMCs Interval 26.7 to 43.0
Geometric Mean of Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) Month 13	287.1 SFC/million PBMCs Interval 201.3 to 409.5	33.2 SFC/million PBMCs Interval 28.8 to 38.2
Geometric Mean of Interferon-gamma (IFN-gamma) T-Cells Responses Analyzed by Enzyme-linked Immunospot Assay (ELISpot) Month 24	172.7 SFC/million PBMCs Interval 117.0 to 254.8	30.8 SFC/million PBMCs Interval 29.2 to 32.5

SECONDARY outcome

Timeframe: Month 7 up to Month 24

Population: PP population set included participants from the FAS; all randomized participants who received at least one study vaccine administration) who were HIV-1 uninfected 4 weeks after the third vaccination visit, who received all planned vaccinations at the first 3 vaccination visits within the respective visit windows and had no other major protocol deviations that were judged to possibly impact the efficacy of the vaccine.

Number of participants with viral sequences were reported. Viral sequencing was conducted on the earliest available plasma specimens with positive HIV-1 ribose nucleic acid polymerase chain reaction (RNA PCR) tests from study participants who were diagnosed with HIV-1 infection.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1080 Participants Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1108 Participants Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Number of Participants With Viral Sequences	51 Participants	63 Participants

Adverse Events

Group 1: Ad26.Mos.HIV Vaccine

Serious events: 49 serious events

Other events: 798 other events

Deaths: 5 deaths

Group 2: Placebo

Serious events: 37 serious events

Other events: 806 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Group 1: Ad26.Mos.HIV Vaccine n=1317 participants at risk Participants received adenovirus serotype 26-Mosaic-Human Immunodeficiency Virus (Ad26.Mos4.HIV) 5\*10\^10 virus particles (vp) per 0.5 milliliter (mL) via Intramuscular (IM) injection at Months 0, 3, 6, and 12 and Clade C glycoprotein (gp) 140 (250 \[micrograms\] mcg) mixed with aluminum phosphate adjuvant 425 mcg per 0.5 mL IM injection at Months 6 and 12.	Group 2: Placebo n=1319 participants at risk Participants received Placebo matching to Ad26.Mos4.HIV as 0.5 mL via IM injection at Months 0, 3, 6, and 12 and Placebo matching to Clade C gp140/aluminum phosphate adjuvant as 0.5 mL IM injection at Months 6 and 12.
Infections and infestations Genitourinary chlamydia infection	40.1% 528/1317 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.	40.0% 527/1319 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.
Infections and infestations Genitourinary tract gonococcal infection	20.4% 269/1317 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.	21.8% 288/1319 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.
Infections and infestations Syphilis	5.2% 69/1317 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.	6.0% 79/1319 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.
Infections and infestations Upper respiratory tract infection	6.0% 79/1317 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.	5.8% 77/1319 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.
Infections and infestations Vulvovaginitis trichomonal	18.6% 245/1317 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.	18.1% 239/1319 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.
Reproductive system and breast disorders Vaginal discharge	7.7% 102/1317 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.	8.6% 113/1319 • Up to Month 36 Full analysis set (FAS) included all randomized participants who received at least 1 vaccine administration. Here, N (total number of participants at risk) signifies participants who were assessed for AEs as safety analyses were performed based on the actual treatment that the participants received. Therefore, number of participants affected for all-cause mortality are different in participant flow section and adverse event section.

Additional Information

CLINICAL FRANCHISE LEADER

Janssen Vaccines & Prevention B.V

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER