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.

NCT02075541 | Completed Phase 2 Results

• 2 other identifiers: 2001572013-003062-13
• Study Type: interventional
• Target: 145
• Locations: 2 countries
• Sites: 14

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.

Conditions

Respiratory Disorders

Keywords

Immunogenicity; Observer-blind; Reactogenicity; Chronic Obstructive Pulmonary Disease; Safety

Outcome Measures

Primary Outcomes (16)

• Number of Subjects With Any Solicited Local Adverse Events (AEs).

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.

  During a 7-day follow-up period (from Day 0 to Day 6) after first dose.

• Number of Subjects With Any Solicited Local AEs.

  Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.

  During a 7-day follow-up period (from Day 60 to Day 66) after second dose.

• Number of Subjects With Any Solicited General AEs.

  Assessed solicited general symptoms are fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), headache, fever \[defined as oral temperature equal to or above 37.5 degrees Celsius (°C)\]. Any = occurrence of the symptom regardless of intensity grade.

  During a 7-day follow-up period (from Day 0 to Day 6) following the first dose.

• Number of Subjects With Any Solicited General AEs

  Assessed solicited general symptoms are fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), headache, fever (defined as oral temperature equal to or above 37.5 °C). Any = occurrence of the symptom regardless of intensity grade.

  During a 7-day follow-up period (from Day 60 to Day 66) following the second dose.

• Number of Subjects With Any Unsolicited AEs.

  Assessed unsolicited AEs covered any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.

  During the 30-day follow-up period (from Day 0 to Day 29) following the first dose.

• Number of Subjects With Any Unsolicited AEs

  Assessed unsolicited AEs covered any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination.

  During the 30-day follow-up period (from Day 60 to Day 89) following the second dose.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 0.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 7.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 30.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 60.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 67.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 90.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 270.

• Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.

  Assessed haematological parameters are complete blood cell count: Leukocytes \[white blood cells (WBC)\], differential count (basophils, eosinophils, lymphocytes, monocytes, neutrophils), platelets count, and hemoglobin level below or above the normal laboratory ranges tabulated by time point. Assessed biochemical parameters are alanine aminotransferase (ALT), aspartate aminotransferase (AST) or creatinine below or above the normal laboratory ranges tabulated by time point.

  At Day 450.

• Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs).

  pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

  From first vaccination (Day 0) up to study conclusion (Day 450).

• Number of Subjects With Any Serious Adverse Events (SAEs).

  SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity or are a congenital anomaly/ birth defect in the offspring of a study subject.

  From first vaccination (Day 0) up to study conclusion (Day 450).

Secondary Outcomes (5)

• Concentration of Anti Protein D (Anti-PD) Total Immunoglobulin G (IgG) Antibodies Against the NTHi Vaccine Antigens.

  At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450.

• Concentration of Anti Protein E (Anti-PE) Total IgG Antibodies Against the NTHi Vaccine Antigens.

  At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450

• Concentration of Anti-PilA Total IgG Antibodies Against the NTHi Vaccine Antigens.

  At Day 0, Day 30, Day 60, Day 90, Day 270 and at Day 450.

• Frequency of Specific Cluster of Differentiation 4 (CD4+) T-cells Against NTHi Antigens Collected for Evaluation of Cell-mediated Immune Response.

  At Day 0, Day 90, Day 270 and at Day 450.

• Frequency of Specific CD8+ T-cells Against NTHi Antigens Collected for Evaluation of Cell-mediated Immune Response.

  At Day 0, Day 90, Day 270 and at Day 450.

Study Arms (2)

10-AS01E group

EXPERIMENTAL

Subjects in this group will receive the investigational NTHi vaccine.

Biological: NTHi-10-AS01E

Control group

PLACEBO COMPARATOR

Subjects in this group will receive placebo.

Drug: NaCl Placebo

Interventions

NTHi-10-AS01E BIOLOGICAL

Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

10-AS01E group

NaCl Placebo DRUG

Intramuscular vaccination in the deltoid region of the non-dominant arm according to protocol schedule.

Control group

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (14)

GSK Investigational Site

Eskilstuna, SE-631 88, Sweden

Location

GSK Investigational Site

Gothenburg, SE-413 45, Sweden

Location

GSK Investigational Site

Örebro, SE-703 62, Sweden

Location

GSK Investigational Site

Llanelli, Carmarthenshire, SA14 8QF, United Kingdom

Location

GSK Investigational Site

Leicester, Leicestershire, LE3 9QP, United Kingdom

Location

GSK Investigational Site

Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom

Location

GSK Investigational Site

Bradford, BD9 6RJ, United Kingdom

Location

GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

Location

GSK Investigational Site

Edinburgh, EH16 4SA, United Kingdom

Location

GSK Investigational Site

Liverpool, L9 7AL, United Kingdom

Location

GSK Investigational Site

Poole, Dorset, BH15 2JB, United Kingdom

Location

GSK Investigational Site

Salford, M6 8HD, United Kingdom

Location

GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

Location

GSK Investigational Site

Wolverhampton, WV10 0QP, United Kingdom

Location

Related Publications (2)

• Baffetta F, Buonsanti C, Moraschini L, Aprea S, Cane M, Lombardi S, Contorni M, Rondini S, Arora AK, Bardelli M, Finco O, Serruto D, Paccani SR. Lung mucosal immunity to NTHi vaccine antigens: Antibodies in sputum of chronic obstructive pulmonary disease patients. Hum Vaccin Immunother. 2024 Dec 31;20(1):2343544. doi: 10.1080/21645515.2024.2343544. Epub 2024 Apr 24.

  PMID: 38655676 DERIVED

• 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.

  PMID: 31447126 DERIVED

MeSH Terms

Conditions

Respiration Disorders; Pulmonary Disease, Chronic Obstructive

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

lp542096@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Study Start: July 8, 2014
• Primary Completion: April 19, 2017
• Study Completion: April 19, 2017
• Last Updated: August 1, 2018
• Results First Posted: August 1, 2018

Record last verified: 2018-06

Locations

GB (11); SE (3)