Clinical trial NCT02547974: A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the Investigational GSK Biologicals' GSK3277511A Vaccine in Adults.
Official title: An Observer-blind Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the Investigational GSK Biologicals' GSK3277511A Vaccine in Adults.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Respiratory Disorders
Keywords: Safety
Immunogenicity
Reactogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-09-14
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety, reactogenicity and immunogenicity of the investigational GSK Biologicals' GSK3277511A vaccine in adults


Eligibility criteria: Inclusion Criteria:

applicable for both Step 1 ((healthy volunteers) and Step 2 (\[ex-\]smokers)

* Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol
* Written informed consent obtained from the subject.
* Female subjects of non-childbearing potential may be enrolled in the study.

  * Non-childbearing potential is defined as pre-menarche, hysterectomy, ovariectomy or post-menopause.
* 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 vacci-nation, and
  * has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

only applicable for Step 1

* A male or female between, and including, 18 and 40 years of age at the time of the Screening Visit.
* Healthy subjects without acute or chronic, clinically sig-nificant pulmonary, cardiovascular, hepatic or renal func-tional abnormality, as determined by physical examination or laboratory screening tests.

only applicable for Step 2

* A male or female between, and including, 50 and 70 years of age at the time of the screening visit.
* Subjects without medical history, clinical finding or laboratory finding which in the opinion of the investigator could pose a safety concern or interfere with the protocol.
* Current or former smoker with a cigarette smoking history ≥ 10 pack-years.

Exclusion Criteria:

applicable for both Step 1 and Step 2

* Use of any investigational or non-registered product other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
* 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.
* Previous vaccination with any vaccine containing NTHi and/or Mcat antigens.
* Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥20 mg/day, or equivalent. Only topical steroids are allowed.
* Administration of long-acting immune-modifying drugs at any time during the study period.
* Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* History of or current autoimmune disease.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature \>= 37.5°C for oral or axillary route. The preferred route for recording temperature in this study will be oral.
  * Subjects with a minor illness without fever may, be enrolled at the discretion of the investigator.
* Current alcoholism and/or drug abuse.
* History of or current condition preventing intramuscular injection as bleeding or coagulation disorder.
* Malignancies within previous 5 years or lymphoproliferative disorders.
* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* Any other condition that the investigator judges may interfere with study findings.

only applicable for Step 1

* 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 vaccine which may be administered ≥ 15 days preceding or following any study vaccine dose.
* Laboratory evidence of clinically significant haematological (complete blood cell count \[RBC, WBC\], WBC differential count \[lymphocytes, neutrophils and eosinophils\], platelets count or haemoglobin level) and biochemical (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] or creatinine) abnormalities as per the opinion of the investigator.

only applicable for Step 2

* 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 licensed vaccine which may be admin-istered ≥ 15 days preceding or following any study vaccine dose.
* Post-bronchodilator FEV1 \< 80% of predicted normal value.
* Diagnosed with a respiratory disorder (e.g. asthma, COPD, sarcoidosis, tuberculosis, bronchiectasis, lung fi-brosis, pulmonary embolism, pneumothorax, or physi-cian confirmed lung cancer). Please note that subjects with mild pulmonary obstruction (i.e. FEV1/ FVC ratio \< 0.7 with FEV1 ≥ 80% of normal predicted values \[GOLD grade 1\]) can be enrolled.
* Has contraindication for spirometry testing (such as recent eye surgery, recent thoracic or abdominal surgery procedures, unstable cardiovascular status, recent myo-cardial infection or pulmonary embolism).
* Laboratory evidence of clinically significant haematological (complete blood cell count \[RBC, WBC\], WBC differential count \[lymphocytes, neutrophils and eosinophils\], platelets count or haemoglobin level) and biochemical (ALT, AST or creatinine) abnormalities.
* Has significant disease, in the opinion of the investigator, likely to interfere with the study and/or likely to cause death within the study duration.

Primary outcomes:
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs)
timeFrame: During a 7-day follow-up period (Day 0 to Day 6) after first dose.
measure: Number of Subjects With Any Solicited Local Adverse Events (AEs)
timeFrame: During a 7-day follow-up period (Day 60 to Day 66) after second dose
measure: Number of Subjects With Any Solicited General Adverse Events (AEs)
timeFrame: During a 7-day follow-up period (Day 0 to Day 6) after first dose.
measure: Number of Subjects With Any Solicited General Adverse Events (AEs)
timeFrame: During a 7-day follow-up period (Day 60 to Day 66) after second dose.
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs).
timeFrame: During a 30-day follow-up period (Day 0 to Day 29) after first dose.
measure: Number of Subjects With Any Unsolicited Adverse Events (AEs)
timeFrame: During a 30-day follow-up period (Day 60 to Day 89) after second dose
measure: Number of Subjects With Any Haematological and Biochemical Laboratory Abnormalities, After Vaccination.
timeFrame: At Day 7, post-dose 1.
measure: Number of Subjects With Any Haematological and Biochemical Laboratory Abnormalities After Vaccination
timeFrame: At Day 60, post-dose 1.
measure: Number of Subjects With Any Haematological and Biochemical Laboratory Abnormalities After Vaccination
timeFrame: At Day 67, post-dose 2.
measure: Number of Subjects With Any Haematological and Biochemical Laboratory Abnormalities After Vaccination
timeFrame: At Day 210, post-dose 2.
measure: Number of Subjects With Any Haematological and Biochemical Laboratory Abnormalities After Vaccination
timeFrame: At Day 420, post-dose 2.
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: From first vaccination up to study conclusion (Day 0 to Day 420)
measure: Number of Subjects With Any Potential Immune-mediated Diseases (pIMDs)
timeFrame: From first vaccination up to study conclusion (Day 0 to Day 420)
Secondary outcomes:
measure: Concentration of Antibodies Against the NTHi-Mcat Anti-PD (Protein D of Haemophilus Influenzae) Vaccine Component
timeFrame: At Day 0 (pre-dose 1); at Day 30 and Day 60 (post-dose 1); at Day 90, Day 210 and Day 420 (post-dose2).
measure: Concentration of Antibodies Against the NTHi-Mcat Anti-PE (Protein E of Haemophilus Influenzae) Vaccine Component
timeFrame: At Day 0 (pre-dose 1); at Day 30 and Day 60 (post-dose 1); at Day 90, Day 210 and Day 420 (post-dose2).
measure: Concentration of Antibodies Against the NTHi-Mcat Anti-PilA (Type IV Pili Subunit of Non-typeable Haemophilus Influenzae) Vaccine Component
timeFrame: At Day 0 (pre-dose 1); at Day 30 and Day 60 (post-dose 1); at Day 90 (post-dose2).
measure: Concentration of Antibodies Against the NTHi-Mcat Anti-PilA (Type IV Pili Subunit of Non-typeable Haemophilus Influenzae) Vaccine Component
timeFrame: At Day 210 and Day 420 (post-dose2).
measure: Concentration of Antibodies Against the NTHi-Mcat Anti-UspA2 (Ubiquitous Surface Protein A2 of Moraxella Catarrhalis) Vaccine Component
timeFrame: At Day 0 (pre-dose 1); at Day 30 and Day 60 (post-dose 1); at Day 90, Day 210 and Day 420 (post-dose2).
measure: Frequency of Specific Cluster of Differentiation (CD)4+ T-cells Against NTHi-Mcat Antigens Collected for the Evaluation of Cell-mediated Immune Response
timeFrame: At Day 0 (pre-dose 1); at Day 60 (post-dose 1); at Day 90, Day 210 and Day 420 (post-dose2).
measure: Frequency of Specific CD8+ T-cells Against NTHi-Mcat Antigens Collected for the Evaluation of Cell-mediated Immune Response
timeFrame: At Day 0 (pre-dose 1); at Day 60 (post-dose 1); at Day 90, Day 210 and Day 420 (post-dose2).
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Wilrijk
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Van Damme P, Leroux-Roels G, Vandermeulen C, De Ryck I, Tasciotti A, Dozot M, Moraschini L, Testa M, Arora AK. Safety and immunogenicity of non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine. Vaccine. 2019 May 21;37(23):3113-3122. doi: 10.1016/j.vaccine.2019.04.041. Epub 2019 Apr 24.