Last reviewed · How we verify

NCT04999111: Amplify

A Study of Ad26.COV2.S Administered as Booster Vaccination in Adults Who Have Previously Received Primary Vaccination With Ad26.COV2.S or BNT162b2

Completed Phase 2 Results posted Last updated 4 February 2025
What this trial tests

Phase 2 trial testing Ad26.COV2.S in Coronavirus Disease in 1,541 participants. Completed in 22 November 2022.

Timeline
6 August 2021
Primary endpoint
27 October 2021
22 November 2022

Quick facts

Lead sponsorJanssen Vaccines & Prevention B.V.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposeprevention
Enrollment1,541
Start date6 August 2021
Primary completion27 October 2021
Estimated completion22 November 2022
Sites21 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Janssen Vaccines & Prevention B.V. — full company profile →

Who can join

18 and older, any sex, with Coronavirus Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cohort 1: Percentage of Participants With Serological Response Against SARS-CoV-2 Original Strain 14 Days After Ad26.COV2.S Booster Vaccination After Completing Primary Vaccination With Ad26.COV2.S Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., on Day 15)

Percentage of participants with serological response against SARS-CoV-2 original strain (Wuhan, 2019, whole genome sequence) 14 days after Ad26.COV2.S booster vaccination after completing primary vaccination with Ad26.COV2.S was reported. A participant was considered a responder if one or both of the following conditions were satisfied: (1) Pre-booster titer less than (\<) lower limit of quantification (LLOQ) and post-booster titer greater than or equal to (\>=) 4\*LLOQ or (2) Pre-booster titer greater than (\>) LLOQ and post-booster titer \>=4\*pre-booster titer value.

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)63.457.7 – 68.9
Cohort 1: Ad26.COV2.S (2.5*10^10 vp)57.952.1 – 63.6
Cohort 1: Ad26.COV2.S (1*10^10 vp)64.553.9 – 74.2
Cohort 1: Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Original Strain 14 Days After Ad26.COV2.S Booster Vaccination After Completing Primary Vaccination With Ad26.COV2.S Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., on Day 15)

GMTs of neutralizing antibodies against SARS-CoV-2 original strain 14 days after Ad26.COV2.S booster vaccination after completing primary vaccination with Ad26.COV2.S (5×10\^10 vp dose level) were reported. GMT against original strain was assessed by virus neutralization assay (VNA).

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)1130989 – 1291
Cohort 1: Ad26.COV2.S (2.5*10^10 vp)915792 – 1058
Cohort 1: Ad26.COV2.S (1*10^10 vp)734564 – 954
Cohort 1: Percentage of Participants With Serological Response Against SARS-CoV-2 Original Strain 28 Days After Primary Vaccination With Ad26.COV2.S Primary · 28 days after primary vaccination with Ad26.COV2.S (Day 29 of study VAC31518COV3001)

Percentage of participants with serological response against SARS-CoV-2 original strain 28 days after primary vaccination with Ad26.COV2.S (5×10\^10 vp dose level) were reported. A participant was considered a responder if one or both of the following conditions were satisfied: (1) Pre-dose titer \<LLOQ and post-vaccination titer \>=4\*LLOQ or (2) Pre-dose titer \>LLOQ and post-vaccination titer \>=4\*pre-dose 1 titer value.

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)15.411.6 – 19.9
Cohort 1: Ad26.COV2.S (2.5*10^10 vp)16.812.9 – 21.4
Cohort 1: Ad26.COV2.S (1*10^10 vp)11.76.4 – 19.2
Cohort 1: GMTs of Neutralizing Antibodies Against SARS-CoV-2 Original Strain 28 Days After Primary Vaccination With Ad26.COV2.S Primary · 28 days after primary vaccination with Ad26.COV2.S (Day 29 of study VAC31518COV3001)

GMTs of neutralizing antibodies against SARS-CoV-2 original strain 28 days after primary vaccination with Ad26.COV2.S (5×10\^10 vp dose level) were reported. GMT against original strain was assessed by VNA.

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)9885 – 113
Cohort 1: Ad26.COV2.S (2.5*10^10 vp)10087 – 115
Cohort 1: Ad26.COV2.S (1*10^10 vp)76NA – 92
Cohort 1: Percentage of Participants With Serological Response Against the Delta Variant 14 Days After Ad26.COV2.S Booster Vaccination (5*10^10 vp Dose Level) After Completing Primary Vaccination With Ad26.COV2.S Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., On Day 15)

Percentage of participants with serological response against leading variant of high consequence or concern (delta variant) 14 days after Ad26.COV2.S booster vaccination (5\*10\^10 vp Dose Level) after completing primary vaccination with Ad26.COV2.S were reported. A participant was considered a responder if one or both of the following conditions were satisfied: (1) Pre-booster titer \<LLOQ and post-booster titer \>=4\*LLOQ or (2) Pre-booster titer \>LLOQ and post-booster titer \>=4\*pre-booster titer value. As specified in the protocol, data for this outcome measure was not collected and anal

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)56.750.9 – 62.4
Cohort 1: GMTs of Neutralizing Antibodies Against the Leading Variant of High Consequence or Concern (Delta Variant) 14 Days After Ad26.COV2.S Booster Vaccination (5*10^10 vp Dose Level) After Completing Primary Vaccination With Ad26.COV2.S Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., On Day 15)

GMTs of neutralizing antibodies against leading variant of high consequence or concern (delta variant) 14 days After Ad26.COV2.S booster vaccination (5\*10\^10 vp dose level) after completing primary vaccination with Ad26.COV2.S were reported. GMT against Delta Variant was assessed by VNA. As specified in the protocol, data for this outcome measure was not collected and analyzed for Cohort 1: Ad26.COV2.S 2.5\*10\^10 vp and 1\*10\^10 vp participants.

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)471411 – 539
Cohort 1: Percentage of Participants With Serological Response Against SARS-CoV-2 Leading Variant of High Consequence or Concern (Delta Variant) 28 Days After Primary Vaccination With Ad26.COV2.S Primary · 28 days after primary vaccination with Ad26.COV2.S (Day 29 of study VAC31518COV3001)

Percentage of participants with serological response against SARS-CoV-2 leading variant of high consequence or concern (delta variant) 28 days after primary vaccination with Ad26.COV2.S (5\*10\^10 vp dose level) were reported. A participant was considered a responder if one or both of the following conditions were satisfied: (1) Pre-dose titer \<LLOQ and post-vaccination titer \>=4\*LLOQ or (2) Pre-dose titer \>LLOQ and post-vaccination titer \>=4\*pre-dose 1 titer value. As specified in the protocol, data for this outcome measure was not collected and analyzed for Cohort 1: Ad26.COV2.S 2.5\*1

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)8.85.9 – 12.5
Cohort 1: GMTs of Neutralizing Antibodies Against the Leading Variant of High Consequence or Concern (Delta Variant) 28 Days After Primary Vaccination With Ad26.COV2.S (5*10^10 vp Dose Level) Primary · 28 days after primary vaccination with Ad26.COV2.S (Day 29 of study VAC31518COV3001)

GMTs of neutralizing antibodies against the leading variant of high consequence or concern (delta variant) 28 days after primary vaccination with Ad26.COV2.S (5\*10\^10 vp dose level) were reported. GMT against Delta variant was assessed by VNA. As specified in the protocol, data for this outcome measure was not collected and analyzed for Cohort 1: Ad26.COV2.S 2.5\*10\^10 vp and 1\*10\^10 vp participants. Lower limit of Quantification (LLOQ) was 65.

GroupValue95% CI
Cohort 1: Ad26.COV2.S (5*10^10 vp)NANA – NA
Cohort 2: Percentage of Participants With Serological Response Against SARS-CoV-2 Original Strain, 14 Days After Ad26.COV2.S Booster Vaccination After Completing 2-dose Primary Vaccination With BNT162b2 Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., On Day 15)

Percentage of participants with serological response against SARS-CoV-2 original strain, 14 days after Ad26.COV2.S booster vaccination after completing 2-dose primary vaccination with BNT162b2 were reported. A participant was considered a responder if at least one of the following conditions were satisfied: (1) If pre-booster 1 titer \<LLOQ, then post-booster titer \>=4\*LLOQ or (2) If pre-booster 1 titer \>LLOQ, then post-booster titer \>=4\*pre-booster value (titer).

GroupValue95% CI
Cohort 2: Ad26.COV2.S (5*10^10 vp)97.094.3 – 98.6
Cohort 2: Ad26.COV2.S (2.5*10^10 vp)90.586.5 – 93.6
Cohort 2: Ad26.COV2.S (1*10^10 vp)89.881.5 – 95.2
Cohort 2: GMTs of Neutralizing Antibodies Against SARS-CoV-2 Original Strain 14 Days After Ad26.COV2.S Booster Vaccination After Completing 2-dose Primary Vaccination With BNT162b2 Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., On Day 15)

GMTs of neutralizing antibodies against SARS-CoV-2 original strain 14 days after Ad26.COV2.S booster vaccination after completing 2-dose primary vaccination with BNT162b2 were reported. GMT against original strain was assessed by VNA.

GroupValue95% CI
Cohort 2: Ad26.COV2.S (5*10^10 vp)44394027 – 4893
Cohort 2: Ad26.COV2.S (2.5*10^10 vp)35663212 – 3958
Cohort 2: Ad26.COV2.S (1*10^10 vp)32182582 – 4010
Cohort 2: GMTs of Neutralizing Antibodies Against SARS-CoV-2 Original Strain 2 Weeks to 2 Months After Completing 2-dose Primary Vaccination With BNT162b2 (Pfizer BNT162b2 External Samples) Primary · 2 weeks to 2 months after primary vaccination with BNT162b2 (up to 1.5 months)

GMTs of neutralizing antibodies against SARS-CoV-2 original strain 2 weeks to 2 months after completing 2-dose primary vaccination with BNT162b2 were reported. GMT against original strain was assessed by VNA.

GroupValue95% CI
Pfizer External Samples12811086 – 1510
Cohort 2: Percentage of Participants With Serological Response Against SARS-CoV-2 Delta Variant 14 Days After Booster Vaccination (5*10^10 vp Dose Level) After Completing 2-dose Primary Vaccination With BNT162b2 Primary · 14 days after Ad26.COV2.S booster vaccination (i.e., On Day 15)

Percentage of participants with serological response against SARS-CoV-2 leading variant of high consequence or concern (Delta) 14 days after booster vaccination (5\*10\^10 vp dose level) after completing 2-dose primary vaccination with BNT162b2 were reported. A participant was considered a responder if at least one of the following conditions was satisfied: (1) If pre-booster 1 titer \<LLOQ, then post-booster titer \>=4\*LLOQ or (2) If pre-booster 1 titer \>LLOQ, then post-booster titer \>=4\*pre-booster value (titer). As specified in the protocol, data for this outcome measure was not collect

GroupValue95% CI
Cohort 2: Ad26.COV2.S (5*10^10 vp)93.690.2 – 96.1

Adverse events — posted to ClinicalTrials.gov

Time frame: From booster vaccination (Day 1) until 1 year post booster vaccination. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: Ad26.COV2.S (5*10^10 vp)
Serious: 11/330 (3%)
Deaths: 1/330
Cohort 1: Ad26.COV2.S (2.5*10^10 vp)
Serious: 7/326 (2%)
Deaths: 1/326
Cohort 1: Ad26.COV2.S (1*10^10 vp)
Serious: 2/116 (2%)
Deaths: 0/116
Cohort 2: Ad26.COV2.S (5*10^10 vp)
Serious: 9/326 (3%)
Deaths: 0/326
Cohort 2: Ad26.COV2.S (2.5*10^10 vp)
Serious: 4/328 (1%)
Deaths: 0/328
Cohort 2: Ad26.COV2.S (1*10^10 vp)
Serious: 2/106 (2%)
Deaths: 0/106

Serious adverse events (44 terms)

ReactionSystemCohort 1: Ad26.COV2.S (5*1…Cohort 1: Ad26.COV2.S (2.5…Cohort 1: Ad26.COV2.S (1*1…Cohort 2: Ad26.COV2.S (5*1…Cohort 2: Ad26.COV2.S (2.5…Cohort 2: Ad26.COV2.S (1*1…
SeizureNervous system disorders
Acute Myocardial InfarctionCardiac disorders
Angina PectorisCardiac disorders
Atrial FibrillationCardiac disorders
Atrial FlutterCardiac disorders
Cardiac ArrestCardiac disorders
Coronary Artery DiseaseCardiac disorders
NauseaGastrointestinal disorders
PancreatitisGastrointestinal disorders
Upper Gastrointestinal HaemorrhageGastrointestinal disorders
AstheniaGeneral disorders
Chest PainGeneral disorders
FatigueGeneral disorders
Non-Cardiac Chest PainGeneral disorders
Systemic Inflammatory Response SyndromeGeneral disorders
Bile Duct StoneHepatobiliary disorders
Biliary ObstructionHepatobiliary disorders
AppendicitisInfections and infestations
DiverticulitisInfections and infestations
EndometritisInfections and infestations
OsteomyelitisInfections and infestations
PneumoniaInfections and infestations
Multiple FracturesInjury, poisoning and procedural complications
Pelvic FractureInjury, poisoning and procedural complications
Post Procedural HaematomaInjury, poisoning and procedural complications
Other adverse events (13 terms — click to expand)

ReactionSystemCohort 1: Ad26.COV2.S (5*1…Cohort 1: Ad26.COV2.S (2.5…Cohort 1: Ad26.COV2.S (1*1…Cohort 2: Ad26.COV2.S (5*1…Cohort 2: Ad26.COV2.S (2.5…Cohort 2: Ad26.COV2.S (1*1…
Vaccination Site PainGeneral disorders
FatigueGeneral disorders
HeadacheNervous system disorders
MyalgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
PyrexiaGeneral disorders
Vaccination Site ErythemaGeneral disorders
Vaccination Site SwellingGeneral disorders
Upper Respiratory Tract InfectionInfections and infestations
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
MalaiseGeneral disorders
Nasal CongestionRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Seizure, Acute Myocardial Infarction, Angina Pectoris, Atrial Fibrillation, Atrial Flutter, Cardiac Arrest, Coronary Artery Disease, Nausea.

Data from ClinicalTrials.gov NCT04999111 adverse events section.

Sponsor's own description

The purposes of this study are to demonstrate the non-inferiority (NI) of the neutralizing antibody response to the original strain 14 days after booster vaccination with Ad26.COV2.S at the different dose levels, administered greater than or equal to (\>=) 6 months after single-dose primary vaccination with Ad26.COV2.S, compared to the neutralizing antibody response to the original strain induced by single-dose primary vaccination with Ad26.COV2.S; To demonstrate the NI of the neutralizing antibody response to the leading variant of high consequence or concern 14 days after booster vaccination with Ad26.COV2.S at the 5\*10\^10 virus particle (vp) dose level, administered \>= 6 months after single-dose primary vaccination with Ad26.COV2.S (5\*10\^10 vp dose level), compared to the neutralizing antibody response to the leading variant of high consequence or concern induced by single-dose primary vaccination with Ad26.COV2.S at the 5\*10\^10 vp dose level, if feasible; To demonstrate the NI of the neutralizing antibody response to the original strain 14 days after booster vaccination with Ad26.COV2.S at the different dose levels administered \>=6 months after completing a 2-dose primary vaccination with Pfizer BNT162b2, compared to the neutralizing antibody response to the original strain induced by 2-dose primary vaccination with Pfizer BNT162b2; To demonstrate the NI of neutralizing antibody response to the leading variant of high consequence or concern 14 days after booster vaccination with Ad26.COV2.S at the 5\*10\^10 vp dose level, administered \>= 6 months after completing a 2-dose primary vaccination with Pfizer BNT162b2, compared to the neutralizing antibody response to the leading variant of high consequence or concern induced by 2-dose primary vaccination with Pfizer BNT162b2, if feasible.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Durability of Heterologous and Homologous COVID-19 Vaccine Boosts.
    Tan CS, Collier AY, Yu J, Liu J, et al · · 2022 · cited 49× · PMID 35947380 · DOI 10.1001/jamanetworkopen.2022.26335
  2. Safety, reactogenicity, and immunogenicity of Ad26.COV2.S as homologous or heterologous COVID-19 booster vaccination: Results of a randomized, double-blind, phase 2 trial.
    Le Gars M, Sadoff J, Cárdenas V, Heerwegh D, et al · · 2024 · cited 1× · PMID 38918103 · DOI 10.1016/j.vaccine.2024.03.079
  3. A randomized, observer-blind, phase 1 study of immune responses to three human adenovirus type 26 vector-based vaccines.
    Hertoghs N, Serroyen J, Tolboom J, van Heesbeen R, et al · · 2026 · PMID 42061096 · DOI 10.1016/j.ebiom.2026.106271
  4. Pre- and post-Ad26.COV2·S booster dose antibody levels predict COVID-19 disease risk.
    Roels S, Bruckner M, Sadoff J, Cárdenas V, et al · · 2024 · PMID 39121698 · DOI 10.1016/j.vaccine.2024.126159

Verify or expand the search:

Other trials of Ad26.COV2.S

Trials testing the same drug.

Other Janssen Vaccines & Prevention B.V. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04999111.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing