A study to evaluate the safety, reactogenicity and immunogenicity of GlaxoSmithKline Biologicals’ investigational vaccine GSK2838504A when administered to chronic obstructive pulmonary disease (COPD) patients with persistent airflow obstruction

• Register: EUCTR
• Last refreshed on: 3 July 2017
• Main ID: EUCTR2013-003062-13-SE
• Date of registration: 23/02/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: A study to evaluate the safety, reactogenicity and immunogenicity of GlaxoSmithKline Biologicals’ investigational vaccine GSK2838504A when administered to chronic obstructive pulmonary disease (COPD) patients with persistent airflow obstruction
• Scientific title: A Phase II, randomised, observer-blind, placebo-controlled, multi-centre study to evaluate the safety, reactogenicity and immunogenicity of GSK Biologicals’ investigational vaccine GSK2838504A, when administered intramuscularly according to a 0, 2 month schedule to COPD patients aged 40 to 80 years - NTHI-004
• Date of first enrolment: 04/03/2015
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003062-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: observer-blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Sweden, United Kingdom

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

Key inclusion & exclusion 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

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 a-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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

COPD
MedDRA version: 17.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855
MedDRA version: 17.1 Level: LLT Classification code 10010953 Term: COPD exacerbation System Organ Class: 100000004855

Intervention(s)

Product Name: NTHi-10-AS01E
Pharmaceutical Form: Powder and suspension for suspension for injection
INN or Proposed INN: Protein D
Current Sponsor code: PD
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-
INN or Proposed INN: PE-PilA
Current Sponsor code: NTHi
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: • Solicted local and general AEs: during a 7-day follow-up period (from day 0 - 6) following each vaccination.
• Unsolicited AEs: During the 30-day follow-up period (from day 0 - 29) following each vaccination.
• Haematological/ biochemical laboratory parameters: at Day 0, Day 7, Day 30, Day 60, Day 67, Day 90, Day 270 and at Day 450.
• pIMDs and SAEs: from first vaccination (Day 0) up to study conclusion (Day 450).

Main Objective: To describe the safety and reactogenicity of the investigational vaccine

Primary end point(s): • Occurrence of each solicited local adverse event (AE), in all subjects.
• Occurrence of each solicited general AE, in all subjects.
• Occurrence of any unsolicited AE, in all subjects.
• Occurrence of each haematological/ biochemical laboratory abnormality, in all subjects.
• Occurrence of any potential immune-mediated disease (pIMD), in all subjects.
• Occurrence of any serious adverse event (SAE), in all subjects.

Secondary Objective: To describe the humoral and cellular immunogenicity of the investigational vaccine

Secondary Outcome(s)

Secondary end point(s): • Anti-PD, anti-PE and anti-PilA total IgG antibody concentrations as measured by ELISA, in all subjects.
• NTHi-specific cell-mediated immune responses as measured by flow cytometry intracellular cytokine staining (ICS), in a sub-cohort of subjects.

Timepoint(s) of evaluation of this end point: • ELISA: at Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450.
• CMI: at Day 0, Day 90, Day 270 and at Day 450.

Secondary ID(s)

200157

2013-003062-13-GB

Source(s) of Monetary Support

GlaxoSmithKline Biologicals