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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03201211

Enrollment

Registered

2017-06-28

Start date

2017-06-22

Completion date

2020-03-19

Last updated

2021-04-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Respiratory Disorders

Keywords

Safety, Immunogenicity

Brief summary

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.

Interventions

BIOLOGICALBlood 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.

BIOLOGICALGSK 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.

BIOLOGICALGSK biologicals investigational NTHi Mcat vaccine containing 10µg of PD, 10µg of PE-PilA, and 3.3µg of UspA2.

DRUGPlacebo

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

51 Years to 73 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Anti-UspA2 Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 26	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.
Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 26	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.
Anti-ubiquitous Surface Protein A2 of Moraxella Catarrhalis (UspA2) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 20	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.
Anti-Protein D (PD) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 20	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).
Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 26	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.
Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 20	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.
Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 26	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.
Anti-type IV Pili Subunit (PilA) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	At Month 20	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.

Secondary

Measure	Time frame	Description
Number of Subjects Reported With Any Potential Immune-mediated Disease (pIMD)	From first visit (Month 20) up to study conclusion (Month 50)	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.
Number of Subjects Reported With Any Serious Adverse Event (SAE)	From first visit (Month 20) up to study conclusion (Month 50)	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.

Countries

Belgium

Participant flow

Participants by arm

Arm	Count
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.	27
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.	26
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.	28
Total	81

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	1	0	0
Overall Study	CONSENT WITHDRAWAL NOT DUE TO ADV. EVENT	0	0	1
Overall Study	OTHER unknown reasons	0	1	0
Overall Study	Protocol Violation	1	0	0

Baseline characteristics

Characteristic	10-10-10-AS	10-10-3-AS	PLACEBO	Total
Age, Continuous	59.7 Years STANDARD_DEVIATION 6.3	59.0 Years STANDARD_DEVIATION 5.9	58.2 Years STANDARD_DEVIATION 6.5	58.9 Years STANDARD_DEVIATION 6.2
Race/Ethnicity, Customized WHITE - CAUCASIAN / EUROPEAN HERITAGE	27 Participants	26 Participants	28 Participants	81 Participants
Sex: Female, Male Female	12 Participants	12 Participants	9 Participants	33 Participants
Sex: Female, Male Male	15 Participants	14 Participants	19 Participants	48 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	1 / 27	0 / 26	0 / 28
other Total, other adverse events	0 / 0	0 / 0	0 / 0
serious Total, serious adverse events	5 / 27	2 / 26	2 / 28

Outcome results

Primary

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.

Time frame: At Month 50

Population: Analysis was performed on the PPS which included all subjects enrolled in this study, who provided informed consent, complied with the eligibility criteria, study procedures and with immunogenicity data for specified antibody at specified timepoint.

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	315.4 EU/mL
10-10-3-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	474.5 EU/mL
PLACEBO	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	101.5 EU/mL

Primary

Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 26

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	373.4 EU/mL
10-10-3-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	537.2 EU/mL
PLACEBO	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	93.2 EU/mL

Primary

Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 32

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	371.8 EU/mL
10-10-3-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	480.8 EU/mL
PLACEBO	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	94.1 EU/mL

Primary

Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 38

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	368 EU/mL
10-10-3-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	490.4 EU/mL
PLACEBO	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	99.8 EU/mL

Primary

Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 44

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	321.4 EU/mL
10-10-3-AS	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	466.2 EU/mL
PLACEBO	Anti-PD Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	95.6 EU/mL

Primary

Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 38

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	596 EU/mL
10-10-3-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	1003.7 EU/mL
PLACEBO	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	20.2 EU/mL

Primary

Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 50

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	491.3 EU/mL
10-10-3-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	827.8 EU/mL
PLACEBO	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	22 EU/mL

Primary

Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 26

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	729.5 EU/mL
10-10-3-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	1258.9 EU/mL
PLACEBO	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	23.1 EU/mL

Primary

Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 32

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	603.9 EU/mL
10-10-3-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	998.1 EU/mL
PLACEBO	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	19.3 EU/mL

Primary

Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 44

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	524.8 EU/mL
10-10-3-AS	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	782.6 EU/mL
PLACEBO	Anti-PE Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	19.4 EU/mL

Primary

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.

Time frame: At Month 32

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	79.7 EU/mL
10-10-3-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	166.9 EU/mL
PLACEBO	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	10 EU/mL

Primary

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.

Time frame: At Month 50

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	54.2 EU/mL
10-10-3-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	106.5 EU/mL
PLACEBO	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	9.8 EU/mL

Primary

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.

Time frame: At Month 44

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	60.8 EU/mL
10-10-3-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	122.5 EU/mL
PLACEBO	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	10.2 EU/mL

Primary

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.

Time frame: At Month 26

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	96.4 EU/mL
10-10-3-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	171.6 EU/mL
PLACEBO	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	13 EU/mL

Primary

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.

Time frame: At Month 38

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	68 EU/mL
10-10-3-AS	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	147.5 EU/mL
PLACEBO	Anti-PilA Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	9.6 EU/mL

Primary

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).

Time frame: At Month 20

Population: Analysis was performed on the Per Protocol Set (PPS) which included all subjects enrolled in this study, who provided informed consent, complied with the eligibility criteria, study procedures and with immunogenicity data for specified antibody at specified timepoint.

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-Protein D (PD) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	382.7 EU/mL
10-10-3-AS	Anti-Protein D (PD) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	511.9 EU/mL
PLACEBO	Anti-Protein D (PD) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	90.5 EU/mL

Primary

Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine

Time frame: At Month 20

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	762.7 EU/mL
10-10-3-AS	Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	1215 EU/mL
PLACEBO	Anti-Protein E (PE) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	21.5 EU/mL

Primary

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.

Time frame: At Month 20

Arm	Measure	Value (GEOMETRIC_MEAN)
10-10-10-AS	Anti-type IV Pili Subunit (PilA) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	121.9 EU/mL
10-10-3-AS	Anti-type IV Pili Subunit (PilA) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	188.3 EU/mL
PLACEBO	Anti-type IV Pili Subunit (PilA) Antibody Concentrations, Measured as Component of the NTHi Mcat Investigational Vaccine	13.8 EU/mL

Primary