Trial Outcomes & Findings for 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 (NCT NCT03964415)

Last Updated: 2024-07-31

Results Overview

Number of participants with a confirmed HIV-1 infections diagnosed between the Month 7 and Month 24 visits (PP set) was reported. The data represents the cumulative incidence of HIV-1 infections.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

3900 participants

Primary outcome timeframe

From Month 7 up to Month 24

Results posted on

2024-07-31

Participant Flow

Participant milestones

Participant milestones
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Overall Study STARTED	1948	1952
Overall Study Treated: Full Analysis Set (FAS)	1942	1945
Overall Study COMPLETED	95	103
Overall Study NOT COMPLETED	1853	1849

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Overall Study Sponsor's decision	1563	1528
Overall Study Lost to Follow-up	139	146
Overall Study Withdrawal by Subject	68	72
Overall Study Physician Decision	34	48
Overall Study Adverse Event	3	0
Overall Study Death	4	6
Overall Study Protocol Violation	1	4
Overall Study Other	35	38
Overall Study Randomized but not treated	6	7

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).	Total n=3887 Participants Total of all reporting groups
Age, Continuous	29.7 years STANDARD_DEVIATION 8.28 • n=113 Participants	29.9 years STANDARD_DEVIATION 8.58 • n=163 Participants	29.8 years STANDARD_DEVIATION 8.43 • n=160 Participants
Sex/Gender, Customized Female (at birth)	9 Participants n=113 Participants	7 Participants n=163 Participants	16 Participants n=160 Participants
Sex/Gender, Customized Male (at birth)	1933 Participants n=113 Participants	1937 Participants n=163 Participants	3870 Participants n=160 Participants
Sex/Gender, Customized Undifferentiated (at birth)	0 Participants n=113 Participants	1 Participants n=163 Participants	1 Participants n=160 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1690 Participants n=113 Participants	1675 Participants n=163 Participants	3365 Participants n=160 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	238 Participants n=113 Participants	246 Participants n=163 Participants	484 Participants n=160 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	14 Participants n=113 Participants	24 Participants n=163 Participants	38 Participants n=160 Participants
Race (NIH/OMB) American Indian or Alaska Native	63 Participants n=113 Participants	59 Participants n=163 Participants	122 Participants n=160 Participants
Race (NIH/OMB) Asian	13 Participants n=113 Participants	12 Participants n=163 Participants	25 Participants n=160 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	3 Participants n=113 Participants	7 Participants n=163 Participants	10 Participants n=160 Participants
Race (NIH/OMB) Black or African American	140 Participants n=113 Participants	161 Participants n=163 Participants	301 Participants n=160 Participants
Race (NIH/OMB) White	868 Participants n=113 Participants	862 Participants n=163 Participants	1730 Participants n=160 Participants
Race (NIH/OMB) More than one race	814 Participants n=113 Participants	809 Participants n=163 Participants	1623 Participants n=160 Participants
Race (NIH/OMB) Unknown or Not Reported	41 Participants n=113 Participants	35 Participants n=163 Participants	76 Participants n=160 Participants
Region of Enrollment Argentina	202 Participants n=113 Participants	203 Participants n=163 Participants	405 Participants n=160 Participants
Region of Enrollment Brazil	425 Participants n=113 Participants	426 Participants n=163 Participants	851 Participants n=160 Participants
Region of Enrollment Italy	46 Participants n=113 Participants	44 Participants n=163 Participants	90 Participants n=160 Participants
Region of Enrollment Mexico	175 Participants n=113 Participants	172 Participants n=163 Participants	347 Participants n=160 Participants
Region of Enrollment Peru	812 Participants n=113 Participants	808 Participants n=163 Participants	1620 Participants n=160 Participants
Region of Enrollment Poland	57 Participants n=113 Participants	60 Participants n=163 Participants	117 Participants n=160 Participants
Region of Enrollment Puerto Rico	5 Participants n=113 Participants	5 Participants n=163 Participants	10 Participants n=160 Participants
Region of Enrollment Spain	128 Participants n=113 Participants	130 Participants n=163 Participants	258 Participants n=160 Participants
Region of Enrollment United States	92 Participants n=113 Participants	97 Participants n=163 Participants	189 Participants n=160 Participants

PRIMARY outcome

Timeframe: From Month 7 up to Month 24

Population: The PP set included all participants in the full analysis set (FAS; all randomized participants who received at least one vaccine administration) population who had a negative HIV test 4 weeks post 3rd vaccination visit (that is, at the Month 7 Visit) and who received all planned vaccinations at the first three vaccination visits within the respective visit windows.

Number of participants with a confirmed HIV-1 infections diagnosed between the Month 7 and Month 24 visits (PP set) was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1525 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1494 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Between the Month 7 and Month 24 Visits (Per-protocol [PP] Set)	65 Participants	58 Participants

PRIMARY outcome

Timeframe: From Month 7 up to Month 30

Population: The PP set included all participants in the FAS (all randomized participants who received at least one vaccine administration) population who had a negative HIV test 4 weeks post 3rd vaccination visit (that is, at the Month 7 Visit) and who received all planned vaccinations at the first three vaccination visits within the respective visit windows.

Number of participants with a confirmed HIV-1 infections diagnosed between the Month 7 and Month 30 visits (PP set) was reported. The data represents the cumulative incidence of HIV-1 infections.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1525 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1494 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Between the Month 7 and Month 30 Visits (PP Set)	71 Participants	67 Participants

SECONDARY outcome

Timeframe: Up to 7 days post each vaccination (dose) on Days 1 (up to Day 8), 84 (up to Day 91), 168 (up to Day 175), and 364 (up to 371)

Population: The FAS set included all randomized participants who received at least one vaccine administration. Here, 'n' (number analyzed) is defined as participants analyzed at specified timepoints.

Number of participants with solicited local AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited local AEs that included injection site pain/tenderness, erythema and swelling at the study vaccine injection site, are used to assess the reactogenicity of the study vaccine and are pre-defined local (injection site) and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Solicited Local Adverse Events (AEs) Up to 7 days post dose on Day 1	1225 Participants	329 Participants
Number of Participants With Solicited Local Adverse Events (AEs) Up to 7 days post dose on Day 84	905 Participants	239 Participants
Number of Participants With Solicited Local Adverse Events (AEs) Up to 7 days post dose on Day 168	1010 Participants	319 Participants
Number of Participants With Solicited Local Adverse Events (AEs) Up to 7 days post dose on Day 364	917 Participants	252 Participants

SECONDARY outcome

Timeframe: Up to 7 days after each vaccination (dose) on Days 1 (up to Day 8), 84 (up to Day 91), 168 (up to Day 175), and 364 (up to 371)

Population: The FAS set included all randomized participants who received at least one vaccine administration. Here, 'n' (number analyzed) is defined as participants analyzed at specified timepoints.

Number of participants with solicited systemic AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Solicited systemic events included events such as fatigue, headache, nausea, and myalgia, for which participants were specifically questioned and which were noted by participants in their participant diary for 7 days post vaccination (day of vaccination and the subsequent 7 days).

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Solicited Systemic Adverse Events (AEs) Up to 7 days post dose on Day 1	1313 Participants	860 Participants
Number of Participants With Solicited Systemic Adverse Events (AEs) Up to 7 days post dose on Day 84	891 Participants	572 Participants
Number of Participants With Solicited Systemic Adverse Events (AEs) Up to 7 days post dose on Day 168	856 Participants	535 Participants
Number of Participants With Solicited Systemic Adverse Events (AEs) Up to 7 days post dose on Day 371	759 Participants	432 Participants

SECONDARY outcome

Timeframe: Up to 28 days after each vaccination (dose) on Days 1 (up to Day 29), 84 (up to Day 112), 168 (up to Day 196), and 364 (up to 392)

Population: The FAS set included all randomized participants who received at least one vaccine administration. Here, 'n' (number analyzed) is defined as participants analyzed at specified timepoints.

Number of participants with unsolicited AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs are all AEs for which the participants were not specifically questioned in the participant's diary.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Unsolicited Adverse Events (AEs) Up to 28 days post dose on Day 1	253 Participants	245 Participants
Number of Participants With Unsolicited Adverse Events (AEs) Up to 28 days post dose on Day 84	190 Participants	191 Participants
Number of Participants With Unsolicited Adverse Events (AEs) Up to 28 days post dose on Day 168	298 Participants	293 Participants
Number of Participants With Unsolicited Adverse Events (AEs) Up to 28 days post dose on Day 364	249 Participants	297 Participants

SECONDARY outcome

Timeframe: Up to 6 months after the last vaccination (up to Month 18)

Population: The FAS set included all randomized participants who received at least one vaccine administration.

Number of participants with AESIs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Thrombotic events and/or thrombocytopenia (defined as platelet count below the lower limit of normal \[LLN\] range for the testing lab) were considered to be potential AESIs.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Adverse Events of Special Interest (AESIs)	4 Participants	2 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Month 40

Population: The FAS set included all randomized participants who received at least one vaccine administration.

Number of participants with MAAEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Medically-attended Adverse Events (MAAEs)	999 Participants	1002 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Month 40

Population: The FAS set included all randomized participants who received at least one vaccine administration.

Number of participants with SAEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Serious Adverse Events (SAEs)	82 Participants	77 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Month 40

Population: The FAS set included all randomized participants who received at least one vaccine administration.

Number of participants who discontinued the study or study intervention due to AEs were reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants Who Discontinued the Study or Study Intervention Due to Adverse Events (AEs)	11 Participants	16 Participants

SECONDARY outcome

Timeframe: Month 0 to 24, Month 0 to 30, Month 0 to 40

Population: The mITT efficacy population included participants in the FAS who were HIV-1 uninfected at the date of the first vaccination.

Number of participants with a confirmed HIV-1 infections diagnosed over time (mITT set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1940 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1938 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat [mITT] Set) Month 0 to 24	124 Participants	123 Participants
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat [mITT] Set) Month 0 to 30	130 Participants	132 Participants
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat [mITT] Set) Month 0 to 40	130 Participants	133 Participants

SECONDARY outcome

Timeframe: Month 7 to 24, Month 7 to 30, Month 7 to 40

Population: The mITT-2 efficacy population included participants in the FAS who had a negative HIV test 4 weeks post third vaccination visit (that is, at the Month 7 Visit).

Number of participants with a confirmed HIV-1 infections diagnosed over time (mITT-2 set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1812 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1796 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-2 [mITT-2] Set) Month 7 to 24	75 Participants	71 Participants
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-2 [mITT-2] Set) Month 7 to 30	81 Participants	80 Participants
Number of Participants With a Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-2 [mITT-2] Set) Month 7 to 40	81 Participants	81 Participants

SECONDARY outcome

Timeframe: Month 7 to 24, Month 7 to 30, Month 7 to 40

Population: The mITT-3 efficacy population included participants in the FAS who had a negative HIV test 4 weeks post third vaccination visit (that is, at the Month 7 Visit) and who received all planned vaccinations at the first three vaccination visits regardless of the fact if the vaccinations were within the visit windows.

Number of participants with confirmed HIV-1 infection diagnosed over time (mITT-3 set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1793 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1775 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-3 [mITT-3] Set) Month 7 to 40	81 Participants	81 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-3 [mITT-3] Set) Month 7 to 24	75 Participants	71 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Modified Intent-to-Treat-3 [mITT-3] Set) Month 7 to 30	81 Participants	80 Participants

SECONDARY outcome

Timeframe: Month 13 to 24, Month 13 to 30, Month 13 to 40

Population: The FIS included participants in the FAS who were HIV-1 uninfected 4 weeks after the fourth vaccination visit (that is, at Month 13 Visit) and who received all planned vaccinations within the respective visit windows.

Number of participants with confirmed HIV-1 infection diagnosed over time (FIS set) were reported. The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1383 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1376 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Full Immunization Analysis Set [FIS]) Month 13 to 24	22 Participants	22 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Full Immunization Analysis Set [FIS]) Month 13 to 30	28 Participants	31 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections Diagnosed Over Time (Full Immunization Analysis Set [FIS]) Month 13 to 40	28 Participants	32 Participants

SECONDARY outcome

Timeframe: Month 7 to 24, Month 7 to 30, Month 7 to 40

Population: The PP set included all participants in the FAS (who received at least one vaccine administration) population who had a negative HIV test 4 weeks post third vaccination visit (that is, at Month 7 Visit) and who received all planned vaccinations at the first 3 vaccination visits within the respective visit windows. Here, 'n' (number analyzed) indicated participants analyzed at specified timepoints.

Number of participants with confirmed HIV-1 infection as assessed by demographic characteristics: age groups was reported. Age groups included 18-20, 21-24, 25-29, 30-34, 35-44, and greater than or equal to (\>=) 45 years. The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1525 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1494 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 40 (Age Group: 21-24 years)	18 Participants	17 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 40 (Age Group: 25-29 years)	22 Participants	22 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 40 (Age Group: 30-34 years)	8 Participants	8 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 40 (Age Group: 35-44 years)	12 Participants	7 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 24 (Age Group: 18-20 years)	8 Participants	7 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 24 (Age Group: 21-24 years)	15 Participants	17 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 24 (Age Group: 25-29 years)	21 Participants	17 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 24 (Age Group: 30-34 years)	7 Participants	7 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 24 (Age Group: 35-44 years)	12 Participants	6 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 24 (Age Group: >=45 years)	2 Participants	4 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 30 (Age Group: 18-20 years)	9 Participants	10 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 30 (Age Group: 21-24 years)	18 Participants	17 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 30 (Age Group: 25-29 years)	22 Participants	21 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 30 (Age Group: 30-34 years)	8 Participants	8 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 30 (Age Group: 35-44 years)	12 Participants	7 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 30 (Age Group: >=45 years)	2 Participants	4 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 40 (Age Group: 18-20 years)	9 Participants	10 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Age Groups Month 7 to 40 (Age Group: >=45 years)	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Month 7 to 24, Month 7 to 30, Month 7 to 40

Number of participants with confirmed HIV-1 infections as assessed by demographic characteristics: region-wise enrollment was reported. Regions were Latin-America (Argentina, Brazil, Mexico, and Peru), North America (Puerto Rico and United States of America), and Europe (Italy, Poland, and Spain). The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1525 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1494 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 24: Europe	2 Participants	3 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 24: Latin America	63 Participants	54 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 24: North America	0 Participants	1 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 30: Latin America	68 Participants	63 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 30: North America	0 Participants	1 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 30: Europe	3 Participants	3 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 40: Latin America	68 Participants	64 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 40: North America	0 Participants	1 Participants
Number of Participants With Confirmed Human Immunodeficiency Virus (HIV)-1 Infections as Assessed by Demographic Characteristics: Region-Wise Enrollment Month 7 to 40: Europe	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1)

Population: The immunogenicity analysis set included participants who acquired HIV-1 (case) and HIV-1 test negative (controls) that were selected for the case-control analysis. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.

Number of participants with an HIV-1 infection by Ad26 at baseline were reported.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=364 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=23 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With an HIV-1 Infection by Adenovirus Serotype 26 (Ad26) at Baseline	204 Participants	10 Participants

SECONDARY outcome

Timeframe: From Day 1 up to Month 40

Population: The immunogenicity analysis set included participants who acquired HIV-1 (case) and HIV-1 test negative (controls) that were selected for the analysis. Here, 'N' (number of participants analyzed) indicates number of participants evaluable for this outcome measure.

Geometric mean antibody titers for Ad26 as determined by VNA were reported.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=364 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=23 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Geometric Mean Antibody Titers For Adenovirus Serotype 26 (Ad26) as Determined by Vector Neutralization Assay (VNA)	66.6 Titers 95% Confidence Interval 54.1 • Interval 54.1 to 82.0	41.3 Titers 95% Confidence Interval 16.1 • Interval 16.1 to 106.2

SECONDARY outcome

Timeframe: Month 7 to 24, Month 7 to 30, Month 7 to 40

Population: The PP set included all subjects in FAS (all randomized participants who received at least one vaccine) set who had a negative HIV test 4 weeks post 3rd vaccination visit (that is, at Month 7 Visit) and who received all planned vaccinations at the first three vaccination visits within respective visit windows. Here, 'N' (number of participants analyzed) is number of participants evaluable for this outcome measure and 'n' (number analyzed) indicated participants analyzed at specified timepoints.

Number of participants with HIV-1 infection by P(r)EP use were reported. P(r)EP was assessed with a 4 item survey. Each item was measured on a scale ranging from 1 (strongly disagree) to 5 (strongly agree). Higher scores indicating higher levels of self-efficacy. If participant showed any evidence of P(r)EP use during the period based on questionnaire responses, concomitant medications or dried blood spot analysis, the response was "yes". The data represents the cumulative incidence of HIV-1 infections at specified intervals.

Outcome measures

Outcome measures
Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1525 Participants Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1494 Participants Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use Month 7 to 24: P(r)EP Use=Y	5 Participants	3 Participants
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use Month 7 to 24: P(r)EP Use=N	60 Participants	55 Participants
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use Month 7 to 30: P(r)EP Use=Y	5 Participants	5 Participants
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use Month 7 to 30: P(r)EP Use=N	66 Participants	62 Participants
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use Month 7 to 40: P(r)EP Use=Y	5 Participants	5 Participants
Number of Participants With HIV-1 Infection by Pre/Post-exposure Prophylaxis (P[r]EP) Use Month 7 to 40: P(r)EP Use=N	66 Participants	63 Participants

Adverse Events

Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140

Serious events: 82 serious events

Other events: 1687 other events

Deaths: 4 deaths

Group 2: Placebo

Serious events: 77 serious events

Other events: 1348 other events

Deaths: 6 deaths

Serious adverse events

Other adverse events

Additional Information

Medical 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 and its partners for review at least 21 days before submission for publication or presentation. At the request of the sponsor and/or partners, such submission may be delayed up to 60 days. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER

Measure	Group 1: Ad26.Mos4.HIV + Clade C and Mosaic gp140 n=1942 participants at risk Participants received adenovirus serotype 26.Mosaic 4.human immunodeficiency virus (Ad26.Mos4.HIV) 5\*10\^10 viral particles (vp) intramuscular (IM) injection into the deltoid muscle as a monotherapy at Months 0 (Day 1) and 3 (Day 84) (preferably the deltoid of the non-dominant upper arm) along with adjuvanted protein formulation consisting of Clade C protein 80 micrograms (mcg), Mosaic protein 75 mcg and adjuvanted aluminum phosphate 425 mcg, into the deltoid muscle at Months 6 (Day 168) and 12 (Day 364) (different deltoid for each injection).	Group 2: Placebo n=1945 participants at risk Participants received placebo into the deltoid muscle at Months 0 (Day 1), 3 (Day 84; 1 injection), 6 (Day 168) and 12 (Day 364; 2 injections).
Gastrointestinal disorders Diarrhoea	2.6% 51/1942 • Number of events 60 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	2.8% 54/1945 • Number of events 61 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Gastrointestinal disorders Nausea (Solicited)	26.8% 520/1942 • Number of events 758 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	18.6% 361/1945 • Number of events 552 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Gastrointestinal disorders Vomiting (Solicited)	6.6% 128/1942 • Number of events 154 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	4.4% 85/1945 • Number of events 115 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
General disorders Chills (Solicited)	44.1% 857/1942 • Number of events 1405 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	17.6% 342/1945 • Number of events 533 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
General disorders Fatigue (Solicited)	68.1% 1323/1942 • Number of events 3376 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	47.7% 928/1945 • Number of events 2018 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
General disorders Pyrexia (Solicited)	20.6% 400/1942 • Number of events 508 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	7.0% 137/1945 • Number of events 174 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
General disorders Vaccination Site Erythema (Solicited)	2.4% 47/1942 • Number of events 66 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	0.36% 7/1945 • Number of events 7 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
General disorders Vaccination Site Pain (Solicited)	78.2% 1519/1942 • Number of events 5543 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	35.7% 695/1945 • Number of events 1521 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
General disorders Vaccination Site Swelling (Solicited)	4.6% 89/1942 • Number of events 144 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	0.46% 9/1945 • Number of events 10 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Anal Chlamydia Infection	1.1% 22/1942 • Number of events 22 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	2.0% 39/1945 • Number of events 39 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations COVID-19	3.9% 75/1942 • Number of events 76 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	4.1% 79/1945 • Number of events 81 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Gastroenteritis	0.82% 16/1942 • Number of events 16 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.2% 23/1945 • Number of events 23 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Influenza	1.8% 34/1942 • Number of events 35 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.7% 34/1945 • Number of events 38 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Nasopharyngitis	1.3% 25/1942 • Number of events 25 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.4% 28/1945 • Number of events 29 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Oropharyngeal Gonococcal Infection	1.4% 27/1942 • Number of events 28 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	2.1% 40/1945 • Number of events 43 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Pharyngitis	1.0% 20/1942 • Number of events 22 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.0% 20/1945 • Number of events 21 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Proctitis Gonococcal	1.7% 33/1942 • Number of events 33 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.6% 32/1945 • Number of events 33 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Syphilis	1.2% 24/1942 • Number of events 25 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	2.1% 40/1945 • Number of events 41 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Infections and infestations Upper Respiratory Tract Infection	1.5% 29/1942 • Number of events 31 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.4% 27/1945 • Number of events 28 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Musculoskeletal and connective tissue disorders Arthralgia (Solicited)	41.5% 806/1942 • Number of events 1503 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	19.5% 380/1945 • Number of events 639 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Musculoskeletal and connective tissue disorders Myalgia (Solicited)	57.9% 1124/1942 • Number of events 2333 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	28.9% 563/1945 • Number of events 991 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Nervous system disorders Headache (Solicited)	60.8% 1181/1942 • Number of events 2550 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	44.4% 863/1945 • Number of events 1834 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.
Vascular disorders Hypertension	0.88% 17/1942 • Number of events 18 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.	1.2% 24/1945 • Number of events 25 • Unsolicited AEs: 28 days after each vaccination (up to Day 392); Solicited AEs: 7 days after each vaccination (up to Day 371); All-cause mortality and SAE: From Day 1 up to Month 40 The full analysis set (FAS) set included all randomized participants who received at least one vaccine administration.