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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck
ClinicalTrials.gov Identifier:
NCT01119703
First received: May 5, 2010
Last updated: October 16, 2012
Last verified: October 2012
History of Changes
  Purpose

This study evaluated whether it is possible in healthy elderly participants to generate baseline biomarker-based prediction rules (PdR) for vaccine response (post baseline absolute serum antibody titer) using each of the protocol selected vaccines separately; and examined the rank correlation coefficients of pairs of post vaccination antibody titers within the same elderly individuals.


Condition Intervention
Vaccine Response Impaired
 Biological: Tetanus & Diphtheria booster vaccine (Td)
Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]
Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Phase I, Open-Label Observational Study to Develop a Prospective Predictor of Vaccine Hyporesponse in Healthy Elderly Subjects

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Merck:

Primary Outcome Measures:
  • Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Baseline and 1 month after final vaccination ] [ Designated as safety issue: No ]
    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).

  • Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Baseline and 1 month after final vaccination ] [ Designated as safety issue: No ]
    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).

  • Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Baseline and 1 month after final vaccination ] [ Designated as safety issue: No ]
    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).

  • Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Baseline and 3 weeks after final vaccination ] [ Designated as safety issue: No ]
    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).

  • Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants. [ Time Frame: 3 weeks or 1 month after each final vaccination ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • 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. [ Time Frame: Day 7 and 1 month after final vaccination ] [ Designated as safety issue: No ]
    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).

  • Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Day 7 and 1 month after each final vaccination ] [ Designated as safety issue: No ]
    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).

  • Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Day 7 and 1 month after final vaccination ] [ Designated as safety issue: No ]
    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).

  • Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants. [ Time Frame: Day 7 and 3 weeks after final vaccination ] [ Designated as safety issue: No ]
    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).


Biospecimen Retention:   Samples With DNA

Cryopreserved peripheral blood mononuclear cells (PBMCs) obtained from whole blood samples.


Enrollment: 174
Study Start Date: July 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Arm 1: Healthy, elderly participants
Healthy participants 65 years old and older.
 Biological: Tetanus & Diphtheria booster vaccine (Td)
Tetanus & Diphtheria booster vaccine (Td), single intramuscular dose
Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]
TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine], intramuscular, two doses of standard three dose regimen (opposite arms)
Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)
Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen
Arm 2: Healthy, young, participants
Healthy participants 25 to 40 years old.
 Biological: Tetanus & Diphtheria booster vaccine (Td)
Tetanus & Diphtheria booster vaccine (Td), single intramuscular dose
Biological: TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine]
TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine], intramuscular, two doses of standard three dose regimen (opposite arms)
Biological: Dukoral® Traveler's Diarrhea Vaccine (WC/rBS)
Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen

  Eligibility

Ages Eligible for Study:   25 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Adults 25 to 40 years old or 65 years and older

Criteria

Inclusion Criteria:

  • Male or female aged 25 to 40 years old or 65 years of age or older at the prestudy (screening) visit
  • Has no fever on day of screening
  • Lacks Hepatitis B surface antigen seroreactivity
  • If female 25 to 40 years of age, is not pregnant nor breastfeeding, and agrees to use effective contraception

Exclusion Criteria:

  • Has a prior history of Hepatitis B Virus infection
  • Has BMI (Body Mass Index) >35
  • If female 25 to 40 years of age, is pregnant, or expecting to conceive, donate eggs or breastfeed
  • Has received immune globulin and/or blood products within 3 months prior to first dose received
  • Has a history of immunosuppression resulting from disease (e.g., malignancy; human immunodeficiency virus [HIV] infection), or is currently taking corticosteroids or other immunosuppressive/cytotoxic therapy (cancer chemotherapy or organ transplantation)
  • Has an active neoplastic disease
  • Has had any infection including upper respiratory viral syndrome in the 6 weeks prior to planned collection of baseline laboratory samples
  • Has received a live virus vaccine or an inactivated vaccine or is scheduled to receive a live virus vaccine or an inactivated vaccine in the period from 6 weeks prior to receipt of the first vaccine through the completion of all study visits
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01119703

Sponsors and Collaborators
Merck
Investigators
Principal Investigator: Francois St-Maurice, MD Anapharm
Principal Investigator: Denis Audet, MD Anapharm
  More Information

No publications provided

Responsible Party: Merck
ClinicalTrials.gov Identifier: NCT01119703     History of Changes
Other Study ID Numbers: 2010_024, MK-0000-131
Study First Received: May 5, 2010
Results First Received: October 16, 2012
Last Updated: October 16, 2012
Health Authority: Canada: Health Canada

Keywords provided by Merck:
Vaccine Hyporesponse

ClinicalTrials.gov processed this record on May 19, 2013