A Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the Investigational GSK Biologicals' GSK3277511A Vaccine in Adults.

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Respiratory Disorders

Treatments: Biological: Formulation 2 (adjuvanted): NTHi/Mcat vaccine GSK3277513A; Drug: Placebo; Biological: Formulation 3 (adjuvanted): NTHi/Mcat vaccine GSK3339036A; Biological: Formulation 1 (plain): NTHi/Mcat vaccine GSK3277513A

Study type: Interventional

Funder types: Industry

Identifiers

NCT02547974

2015-000378-36 (EudraCT Number)

201281

Details and patient eligibility

About

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

Enrollment: 120 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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120 participants in 4 patient groups, including a placebo group

GSK3277513A F1 Group

Experimental group

Description:

Subjects, 18 - 40 years, receiving two doses of the non adjuvanted GSK Biologicals' NTHi Mcat investigational vaccine (GSK3277513A ) containing formulation 1 (F1) of PD, PE-PilA and UspA2 during Step 1 of the study. Intramuscular injection should be done in the deltoid of the non-dominant arm. In case it is not possible to inject in the non dominant arm, an injection in the dominant arm may be performed.

Treatment:

Biological: Formulation 1 (plain): NTHi/Mcat vaccine GSK3277513A

GSK3277513A F2 Group

Experimental group

Description:

Subjects, 50 - 70 years, receiving two doses of the GSK Biologicals' NTHi-Mcat investigational vaccine(GSK3277513A) containing formulation 2 (F2) (adjuvanted) of PD, PE-PilA and UspA2 during Step 2 of the study. Intramuscular injection should be done in the deltoid of the non-dominant arm. In case it is not possible to inject in the non dominant arm, an injection in the dominant arm may be performed.

Treatment:

Biological: Formulation 2 (adjuvanted): NTHi/Mcat vaccine GSK3277513A

GSK3277513A F3 Group

Experimental group

Description:

Subjects, 50 - 70 years, receiving two doses of the GSK Biologicals' NTHi-Mcat investigational vaccine(GSK3277513A) containing formulation 3 (F3) (adjuvanted) of PD, PE-PilA and UspA2 during Step 2 of the study. Intramuscular injection should be done in the deltoid of the non-dominant arm. In case it is not possible to inject in the non dominant arm, an injection in the dominant arm may be performed.

Treatment:

Biological: Formulation 3 (adjuvanted): NTHi/Mcat vaccine GSK3339036A

Placebo Group

Placebo Comparator group

Description:

Subjects, 18 - 40 years, receiving two doses of placebo (saline solution) during Step 1 of the study and subjects, 50 - 70 years, receiving two doses of placebo (saline solution) during Step 2 of the study. Intramuscular injection should be done in the deltoid of the non-dominant arm. In case it is not possible to inject in the non dominant arm, an injection in the dominant arm may be performed.

Treatment:

Drug: Placebo