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

NCT01119703 | Completed Results

• 2 other identifiers: 0000-131MK-0000-131
• Study Type: observational
• Target: 174
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Vaccine Response Impaired

Keywords

Vaccine Hyporesponse

Outcome Measures

Primary Outcomes (5)

• Antibody Titer Responses to Hepatitis B Virus Surface Antigen (HBV sAg) Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.

  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).

  Baseline and 1 month after final vaccination

• Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.

  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).

  Baseline and 1 month after final vaccination

• Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.

  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).

  Baseline and 1 month after final vaccination

• Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Pre-vaccination Biomarkers in Healthy, Elderly Participants.

  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).

  Baseline and 3 weeks after final vaccination

• Post-vaccination Antibody Titer Responses to Different Vaccines in Healthy, Elderly, Participants.

  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).

  3 weeks or 1 month after each final vaccination

Secondary Outcomes (4)

• 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.

  Day 7 and 1 month after final vaccination

• Antibody Titer Responses to Tetanus Booster Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.

  Day 7 and 1 month after each final vaccination

• Antibody Titer Responses to Reduced Diphtheria Toxin Vaccine, Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.

  Day 7 and 1 month after final vaccination

• Antibody Titer Responses to Oral Cholera Vaccine (WC/rBS), Measured and Predicted Based on Early Post-vaccination Biomarkers in Healthy, Elderly Participants.

  Day 7 and 3 weeks after final vaccination

Study Arms (2)

Arm 1: Healthy, elderly participants

Healthy participants 65 years old and older.

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

Arm 2: Healthy, young, participants

Healthy participants 25 to 40 years old.

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

Interventions

Tetanus & Diphtheria booster vaccine (Td) BIOLOGICAL

Tetanus \& Diphtheria booster vaccine (Td), single intramuscular dose

Arm 1: Healthy, elderly participants; Arm 2: Healthy, young, participants

TwinrixTM [Hepatitis A Inactivated & Hepatitis B (Recombinant) Vaccine] BIOLOGICAL

TwinrixTM \[Hepatitis A Inactivated \& Hepatitis B (Recombinant) Vaccine\], intramuscular, two doses of standard three dose regimen (opposite arms)

Arm 1: Healthy, elderly participants; Arm 2: Healthy, young, participants

Dukoral® Traveler's Diarrhea Vaccine (WC/rBS) BIOLOGICAL

Dukoral® Traveler's Diarrhea Vaccine, recombinant Cholera toxin B subunit (WC/rBS), standard two oral doses per treatment regimen

Arm 1: Healthy, elderly participants; Arm 2: Healthy, young, participants

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adults 25 to 40 years old or 65 years and older

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Biospecimen

Retention: SAMPLES WITH DNA

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

MeSH Terms

Interventions

Tetanus Toxoid; Hepatitis B Vaccines; Vaccines

Intervention Hierarchy (Ancestors)

Toxoids; Biological Products; Complex Mixtures; Viral Hepatitis Vaccines; Viral Vaccines

Results Point of Contact

• Title: Vice President, Late Stage Development Group Leader
• Organization: Merck Sharp & Dohme Corp

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Francois St-Maurice, MD

  Anapharm

  PRINCIPAL INVESTIGATOR

• Denis Audet, MD

  Anapharm

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2010
• First Posted: May 7, 2010
• Study Start: July 1, 2010
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: December 29, 2015
• Results First Posted: November 22, 2012

Record last verified: 2015-11