Trial Outcomes & Findings for Vaccine Hyporesponse in Healthy Elderly Participants (MK-0000-131 AM2) (NCT NCT01119703)

NCT ID: NCT01119703

Last Updated: 2015-12-29

Results Overview

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Recruitment status

COMPLETED

Target enrollment

174 participants

Primary outcome timeframe

Baseline and 1 month after final vaccination

Results posted on

2015-12-29

Participant Flow

Participant milestones

Participant milestones
Measure	Younger Participants Participants 25 to 40 years of age.	Elderly Participants Participants 65 years old and older.
Overall Study STARTED	30	144
Overall Study COMPLETED	30	143
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Younger Participants Participants 25 to 40 years of age.	Elderly Participants Participants 65 years old and older.
Overall Study Adverse Event	0	1

Baseline Characteristics

Vaccine Hyporesponse in Healthy Elderly Participants (MK-0000-131 AM2)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Younger Participants n=30 Participants Aged 25 to 40 years old	Elderly Participants n=144 Participants Aged 65 years and older	Total n=174 Participants Total of all reporting groups
Age, Continuous	33.9 Years STANDARD_DEVIATION 3.6 • n=5 Participants	70.2 Years STANDARD_DEVIATION 4.1 • n=7 Participants	63.9 Years STANDARD_DEVIATION 14.3 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	77 Participants n=7 Participants	95 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	67 Participants n=7 Participants	79 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 1 month after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on enzyme linked immunosorbent assay (ELISA), and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by messenger RNA (mRNA) profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	2.27 ln International Units Standard Deviation 1.24
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	2.12 ln International Units Standard Deviation 1.91

PRIMARY outcome

Timeframe: Baseline and 1 month after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	1.40 ln International Units Standard Deviation 1.24
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	1.32 ln International Units Standard Deviation 1.84

PRIMARY outcome

Timeframe: Baseline and 1 month after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	-0.43 ln International Units Standard Deviation 1.25
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	-0.46 ln International Units Standard Deviation 1.77

PRIMARY outcome

Timeframe: Baseline and 3 weeks after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected prior to vaccination at baseline, to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	5.24 ln International Units Standard Deviation 0.99
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	5.20 ln International Units Standard Deviation 1.55

PRIMARY outcome

Timeframe: 3 weeks or 1 month after each final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to each of these four antigens were then measured 1 month after each final vaccination (3 weeks for cholera toxin), based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. Tetanus	1.32 ln International Units Standard Deviation 1.84
Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. Hepatitis B	2.12 ln International Units Standard Deviation 1.91
Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. Diphtheria	-0.46 ln International Units Standard Deviation 1.77
Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. Cholera	5.20 ln International Units Standard Deviation 1.55

SECONDARY outcome

Timeframe: Day 7 and 1 month after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to HBV sAg were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected at 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log (ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	2.25 ln International Units Standard Deviation 1.24
Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	2.12 ln International Units Standard Deviation 1.91

SECONDARY outcome

Timeframe: Day 7 and 1 month after each final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to tetanus were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	1.43 ln International Units Standard Deviation 1.27
Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	1.32 ln International Units Standard Deviation 1.84

SECONDARY outcome

Timeframe: Day 7 and 1 month after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to diphtheria were then measured 1 month after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	-0.37 ln International Units Standard Deviation 1.36
Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	-0.46 ln International Units Standard Deviation 1.77

SECONDARY outcome

Timeframe: Day 7 and 3 weeks after final vaccination

Population: Healthy participants 65 years of age and older who were treated with all three vaccines, and had their post-vaccination titers measured. Results from comparing titers and biomarker responses between younger and older cohorts are exploratory, and therefore not reported.

Healthy elderly participants were simultaneously vaccinated at baseline with hepatitis vaccine, tetanus-diphtheria booster vaccine, and cholera vaccine. Antibody titers to cholera were then measured 3 weeks after final vaccination, based on ELISA, and are defined as standardized "international units" of reactivity converted from optical densities, transformed to natural log (ln). In order to predict antibody responses blood samples were collected 7 days post-baseline vaccination to measure a wide variety of biomarkers by mRNA profiling, biochemical and flow cytometric assays. These biomarkers were then used in a machine-learning (random-forest based) model to predict antibody titers, transformed to natural log(ln).

Outcome measures

Outcome measures
Measure	Elderly Participants n=143 Participants Healthy participants 65 years of age and older.
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Predicted Titer	5.24 ln International Units Standard Deviation 0.96
Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. Measured Titer	5.20 ln International Units Standard Deviation 1.55

Adverse Events

All Participants

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	All Participants n=174 participants at risk Participants who received at least one dose of each vaccine
General disorders Injection Site Pain	8.0% 14/174

Additional Information

Vice President, Late Stage Development Group Leader

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The SPONSOR must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER