Clinical trial NCT02075541: A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GlaxoSmithkline (GSK) Biologicals' Investigational Vaccine GSK2838504A When Administered to Chronic Obstructive Pulmonary Disease (COPD) Patients With Persistent Airflow Obstruction.
Official title: An Observer-blind Study to Evaluate the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Investigational Vaccine GSK2838504A When Administered to Chronic Obstructive Pulmonary Disease (COPD) Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Respiratory Disorders
Keywords: Immunogenicity
Observer-blind
Reactogenicity
Chronic Obstructive Pulmonary Disease
Safety
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-03-03
Enrollment: 145
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this Phase II study is to assess the safety, reactogenicity and immunogenicity of the investigational Non-typeable Haemophilus influenzae (NTHi) vaccine in patients with moderate and severe persistent airflow obstruction.


Eligibility criteria: Inclusion Criteria:

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* A male or female between, and including, 40 and 80 years of age at the time of the first vaccination.
* Written informed consent obtained from the subject.
* Confirmed diagnosis of COPD with forced expiratory volume in 1 second (FEV1) over forced vital capacity (FVC) ratio (FEV1/FVC) \< 0.7, AND FEV1 \< 80% and ≥ 30% predicted.
* Current or former smoker with a cigarette smoking history of ≥ 10 pack-years.
* Stable COPD patient with documented history of at least 1 moderate or severe acute exacerbation of COPD within the 12 months before Screening.
* Regular sputum producer.
* Capable to comply with the daily electronic Diary Card completion throughout the study period, according to investigator's judgement at Visit 1.
* Female subjects of non-childbearing potential may be enrolled in the study.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:

  * has practiced adequate contraception for 30 days prior to vaccination, and
  * has a negative pregnancy test on the day of vaccination, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria:

* 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.
* Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of vaccine, with the exception of any influenza or pneumococcal vaccine which may be administered ≥ 15 days preceding or following any study vaccine dose.
* Previous vaccination with any vaccine containing NTHi antigens.
* Administration of immunoglobulins or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
* Chronic administration of non-steroid immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of immune-mediated disease other than COPD.
* Administration of systemic corticosteroids within the 30 days before Screening.
* Administration of systemic antibiotics within the 30 days before Screening.
* Chronic use of antibiotics for prevention of acute exacerbations of COPD (AECOPD).
* Receiving oxygen therapy.
* Planned lung transplantation.
* Planned/ underwent lung resection surgery.
* Diagnosis of α-1 antitrypsin deficiency as the underlying cause of COPD.
* Diagnosed with a respiratory disorder other than COPD, or chest X-ray/ CT scan revealing evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Subjects with allergic rhinitis can be enrolled.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines and/ or the bronchodilator used for spirometry assessment during the study.
* Contraindication for spirometry testing.
* Clinically significant abnormality in haematology or biochemistry parameter.
* Acute cardiac insufficiency.
* Malignancies within the previous 5 years or lymphoproliferative disorder.
* Any known disease or condition likely to cause death during the study period.
* Acute disease and/ or fever at the time of Screening.

  * Fever is defined as oral or axillary temperature ≥ 37.5°C. The preferred route for recording temperature in this study will be oral.
  * Subjects with acute disease and/ or fever at the time of Screening may be enrolled at a later date if enrolment is still open. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
* Pregnant or lactating female.
* Current alcoholism and/or drug abuse.
* Other condition which the investigator judges may put the safety of the subject at risk through study participation or which may interfere with the study findings.
* Planned move to a location that will complicate participation in the trial through study end.

Primary outcomes:
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs).
timeFrame: During a 7-day follow-up period (from Day 0 to Day 6) after first dose.
measure: Number of Subjects With Any Solicited Local AEs.
timeFrame: During a 7-day follow-up period (from Day 60 to Day 66) after second dose.
measure: Number of Subjects With Any Solicited General AEs.
timeFrame: During a 7-day follow-up period (from Day 0 to Day 6) following the first dose.
measure: Number of Subjects With Any Solicited General AEs
timeFrame: During a 7-day follow-up period (from Day 60 to Day 66) following the second dose.
measure: Number of Subjects With Any Unsolicited AEs.
timeFrame: During the 30-day follow-up period (from Day 0 to Day 29) following the first dose.
measure: Number of Subjects With Any Unsolicited AEs
timeFrame: During the 30-day follow-up period (from Day 60 to Day 89) following the second dose.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 0.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 7.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 30.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 60.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 67.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 90.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 270.
measure: Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
timeFrame: At Day 450.
measure: Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs).
timeFrame: From first vaccination (Day 0) up to study conclusion (Day 450).
measure: Number of Subjects With Any Serious Adverse Events (SAEs).
timeFrame: From first vaccination (Day 0) up to study conclusion (Day 450).
Secondary outcomes:
measure: Concentration of Anti Protein D (Anti-PD) Total Immunoglobulin G (IgG) Antibodies Against the NTHi Vaccine Antigens.
timeFrame: At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450.
measure: Concentration of Anti Protein E (Anti-PE) Total IgG Antibodies Against the NTHi Vaccine Antigens.
timeFrame: At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450
measure: Concentration of Anti-PilA Total IgG Antibodies Against the NTHi Vaccine Antigens.
timeFrame: At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450.
measure: Frequency of Specific Cluster of Differentiation 4 (CD4+) T-cells Against NTHi Antigens Collected for Evaluation of Cell-mediated Immune Response.
timeFrame: At Day 0, Day 90, Day 270 and at Day 450.
measure: Frequency of Specific CD8+ T-cells Against NTHi Antigens Collected for Evaluation of Cell-mediated Immune Response.
timeFrame: At Day 0, Day 90, Day 270 and at Day 450.
Other outcomes:
Locations:
city: Eskilstuna
country: Sweden
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Örebro
country: Sweden
facility: GSK Investigational Site
city: Llanelli
country: United Kingdom
facility: GSK Investigational Site
state: Carmarthenshire
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
state: Leicestershire
city: Stoke on Trent
country: United Kingdom
facility: GSK Investigational Site
state: Staffordshire
city: Bradford
country: United Kingdom
facility: GSK Investigational Site
city: Dundee
country: United Kingdom
facility: GSK Investigational Site
city: Edinburgh
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: Poole, Dorset
country: United Kingdom
facility: GSK Investigational Site
city: Salford
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
city: Wolverhampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Wilkinson TMA, Schembri S, Brightling C, Bakerly ND, Lewis K, MacNee W, Rombo L, Hedner J, Allen M, Walker PP, De Ryck I, Tasciotti A, Casula D, Moris P, Testa M, Arora AK. Non-typeable Haemophilus influenzae protein vaccine in adults with COPD: A phase 2 clinical trial. Vaccine. 2019 Sep 24;37(41):6102-6111. doi: 10.1016/j.vaccine.2019.07.100. Epub 2019 Aug 22.