A Long Term Follow-up Study up to 4 Years After Study Vaccination to Assess Immunogenicity and Safety of the Investigational Vaccine in Adults

A Long-term Follow-up Study of the Investigational GSK Biologicals' GSK3277511A Vaccine in Adults

The purpose of this long-term follow-up of a Phase I study is to evaluate the kinetics of the antibody response to NTHi-Mcat antigens and long-term safety, in subjects aged between 50-71 years at the time of enrolment in the NTHi-Mcat-001 study. These subjects were previously exposed to two adjuvanted formulations of the NTHi-Mcat vaccine administered according to a 0, 2 months schedule in the NTHi-Mcat-001 (201281) study. The subjects that had received saline placebo controls will also be included in this follow-up study to make comparisons with the investigational vaccines. No vaccinations will be administered in this trial.

Study Overview

• Status: Completed
• Conditions: Respiratory Disorders
• Intervention / Treatment: Biological: Blood sampling; Biological: GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, PE-PilA and UspA2.; Biological: GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2.; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 51 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who previously participated in STEP 2 of study NTHi-Mcat-001 (201281), and performed the last study visit (Month 14) and received the 2 study vaccinations.
• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. return for follow-up visits). And subjects' Legally Acceptable Representative(s) [LAR(s)] who, in the opinion of the investigator, can and will comply, with the requirements of the protocol.
• Written informed consent obtained from the subject/ LAR(s) of the subject prior to performance of any study specific procedure.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) during the period starting 30 days before the first follow-up study visit (Month 19 to Month 20), or planned use during the study period.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since the end of the NTHi-Mcat-001 study. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first follow-up visit or planned administration during the study period.
• Current alcoholism and/or drug abuse.
• Has significant disease (including significant neurological or psychological disorders), in the opinion of the investigator, likely to interfere with the study and/or likely to cause death within the study duration.
• Any other condition that the investigator judges may interfere with study findings.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10-10-10-AS; Subjects who received two doses of the AS01E adjuvanted GSK Biologicals' NTHi-Mcat investigational vaccine, containing 10µg of PD, PE-PilA and UspA2, and administered at Month 0 and Month 2 in NTHi-Mcat-001 study (NCT02547974), and were enrolled in the study.	Biological: Blood sampling; A volume of approximately 20 mL of whole blood should be drawn from each subject, at each study visit, for antibody determination and assay validation/development.; Biological: GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, PE-PilA and UspA2.; 2 doses, not administered as part of this study but administered at Day 0 and Day 60 during STEP 2 of NTHi Mcat-001 (201281 - NCT02547974) study, to subjects who were then enrolled in this study. Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.
Experimental: 10-10-3-AS; Subjects who received two doses of the AS01E adjuvanted GSK Biologicals' NTHi-Mcat investigational vaccine, containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2, and administered at Month 0 and Month 2 in NTHi-Mcat-001 study (NCT02547974), and were enrolled in the study.	Biological: Blood sampling; A volume of approximately 20 mL of whole blood should be drawn from each subject, at each study visit, for antibody determination and assay validation/development.; Biological: GSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2.; 2 doses, not administered as part of this study but administered at Day 0 and Day 60 during STEP 2 of NTHi Mcat-001 (201281 - NCT02547974) study, to subjects who were then enrolled in this study. Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.
Placebo Comparator: PLACEBO; Subjects who received two doses of placebo (saline solution), administered at Month 0 and Month 2 in NTHi-Mcat-001 study (NCT02547974) and were enrolled in the study.	Biological: Blood sampling; A volume of approximately 20 mL of whole blood should be drawn from each subject, at each study visit, for antibody determination and assay validation/development.; Drug: Placebo; 2 doses, not administered as part of this study but administered at Day 0 and Day 60 during STEP 2 of NTHi Mcat-001 (201281 - NCT02547974) study, to subjects who were then enrolled in this study. Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Protein D (PD) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted geometric mean concentration (GMC) and their 95% confidence interval (CI) was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the enzyme-linked immunosorbent assay (ELISA) anti-PD assay was 153 ELISA unit per millilitre (EU/mL).	At Month 20
Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.	At Month 26
Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.	At Month 32
Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.	At Month 38
Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.	At Month 44
Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PD assay was 153 EU/mL.	At Month 50
Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.	At Month 20
Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.	At Month 26
Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.	At Month 32
Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the F13ELISA anti-PE assay was 8 EU/mL.	At Month 38
Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.	At Month 44
Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate. The cut-off value of the ELISA anti-PE assay was 8 EU/mL.	At Month 50
Anti-type IV Pili Subunit (PilA) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.	At Month 20
Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.	At Month 26
Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.	At Month 32
Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.	At Month 38
Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.	At Month 44
Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-PilA assay was 7 EU/mL.	At Month 50
Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.	At Month 20
Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.	At Month 26
Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.	At Month 32
Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.	At Month 38
Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.	At Month 44
Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	Adjusted GMC and their 95% CI was calculated. GMCs were estimated using an ANCOVA model including treatment group as fixed effect and Month 0 antibody concentration from NTHi Mcat-001 as covariate.The cut-off value of the ELISA anti-UspA2 assay was 18 EU/mL.	At Month 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reported With Any Serious Adverse Event (SAE)	A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity.	From first visit (Month 20) up to study conclusion (Month 50)
Number of Subjects Reported With Any Potential Immune-mediated Disease (pIMD)	pIMD's are a subset of Adverse Events that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.	From first visit (Month 20) up to study conclusion (Month 50)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2017
• Primary Completion (Actual): March 19, 2020
• Study Completion (Actual): March 19, 2020

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 27, 2017
• First Posted (Actual): June 28, 2017

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: March 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity
• Additional Relevant MeSH Terms: Respiration Disorders; Respiratory Tract Diseases; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 204913; 2016-004248-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No