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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 145
- 试验地点
- 1
- 主要终点
- Number of Subjects With Any Solicited Local Adverse Events (AEs).
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
10-AS01E group
Subjects in this group will receive the investigational NTHi vaccine.
干预措施: NTHi-10-AS01E (Biological)
Control group
Subjects in this group will receive placebo.
干预措施: NaCl Placebo (Drug)
结局指标
主要结局
Number of Subjects With Any Solicited Local Adverse Events (AEs).
时间窗: During a 7-day follow-up period (from Day 0 to Day 6) after first dose.
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
Number of Subjects With Any Unsolicited AEs.
时间窗: During the 30-day follow-up period (from Day 0 to Day 29) following the first dose.
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.
Number of Subjects Reporting Any Potential Immune-mediated Diseases (pIMDs).
时间窗: From first vaccination (Day 0) up to study conclusion (Day 450).
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.
Number of Subjects With Any Solicited Local AEs.
时间窗: During a 7-day follow-up period (from Day 60 to Day 66) after second dose.
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade.
Number of Subjects With Any Solicited General AEs
时间窗: During a 7-day follow-up period (from Day 60 to Day 66) following the second dose.
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.
Number of Subjects With Any Unsolicited AEs
时间窗: During the 30-day follow-up period (from Day 60 to Day 89) following the second dose.
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.
Number of Subjects With Any Solicited General AEs.
时间窗: During a 7-day follow-up period (from Day 0 to Day 6) following the first dose.
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.
Number of Subjects With Each Haematological/ Biochemical Laboratory Abnormality.
时间窗: At Day 450.
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.
Number of Subjects With Any Serious Adverse Events (SAEs).
时间窗: From first vaccination (Day 0) up to study conclusion (Day 450).
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.
次要结局
- 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.)
- 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.)