A Study to Assess the Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' RSV Investigational Vaccine (ChAd155-RSV) (GSK3389245A) in Healthy Adults

Phase 1

Completed

• Conditions: Respiratory Synctial Virus Infections
• Interventions: Drug: Placebo; Biological: GSK3389245A_LD GROUP; Biological: GSK3389245A_HD GROUP; Biological: Bexsero

• Registration Number: NCT02491463
• Lead Sponsor: GlaxoSmithKline

Brief Summary

The purpose of this first time in human (FTiH) study is to assess the safety, reactogenicity and immunogenicity of 2 doses of the RSV investigational vaccine, when administered intramuscularly according to a 0, 1 month schedule, in healthy adults aged 18 to 45 years.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-06-29
• Study First Submitted QC: 2015-07-02
• Study First Posted: 2015-07-08
• Study Start: 2015-07-23
• Primary Completion: 2016-04-08
• Study Completion: 2017-01-26
• Results First Submitted: 2017-04-05
• Status Verified: 2018-05
• Results First Submitted QC: 2018-06-11
• Last Update Submitted: 2018-06-11
• Results First Posted: 2018-08-20
• Last Update Posted: 2018-08-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 73

Inclusion Criteria

• 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 prior to performing any study specific procedure

• A male or female between, and including, 18 and 45 years of age at the time of first vaccination

• Healthy subjects as established by medical history and clinical examination before entering into the study

• 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 vaccina-tion, and
  • has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series

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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 vaccines during the period starting 30 days before the first dose of study vaccines, or planned use during the study period
• Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to study vaccination, or planned administration 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 administration, with the exception of any licensed influenza vaccine which may be administered ≥ 15 days before the first dose and ≥ 15 days after the last dose of study vaccine
• Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccines or planned administration during the study period
• Blood donation within 4 months prior to study entry or planned blood donation at any time during the study
• Previous vaccination against RSV
• Previous vaccination with a recombinant simian or human adenoviral vaccine
• Previous Bexsero or other vaccination against Neisseria meningitidis serogroup B
• History of or current autoimmune disease
• Family history of congenital or hereditary immunodefi-ciency
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccines.
• History of any neurological disorders or seizures
• History of transient thrombocytopenia or neurological complications following any prior vaccination
• Hypersensitivity to latex
• Hypersensitivity to Bexsero's active substances or to any of its excipients
• Allergic reaction to kanamycin
• Any medical condition that in the judgment of the investi-gator would make intramuscular injection unsafe
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination
• Acute disease and/or fever at the time of enrolment
• Acute or chronic, clinically significant pulmonary, cardio-vascular, hepatic or renal functional abnormality, as de-termined by physical examination or laboratory screening tests
• Malignancy within previous 5 years or lymphoproliferative disorders
• Any clinically significant or any ≥ Grade 2 haematological laboratory abnormality
• Body mass index > 40 kg/m2
• Current alcohol and/or drug abuse
• Pregnant or lactating female
• Any other condition that the investigator judges may interfere with study procedures or findings
• Planned move to a location that will prohibit participating in the trial until study end

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	Placebo	Subjects in this group will receive 2 doses, one month apart, of placebo
GSK3389245A_LD GROUP	GSK3389245A_LD GROUP	Subjects in this group will receive 2 doses, one month apart of the GSK3389245A vaccine low dose
GSK3389245A_HD GROUP	GSK3389245A_HD GROUP	Subjects in this group will receive 2 doses, one month apart, of the GSK3389245A vaccine high dose
Bexsero Group	Bexsero	Subjects in this group will receive 2 doses, one month apart, of Bexsero

Primary Outcome Measures

Name	Time	Method
Number of Subjects With Solicited General Symptoms	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited general symptoms were fatigue, fever \[defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)\] gastrointestinal symptoms (gastro) \[nausea, vomiting, diarrhoea and/or abdominal pain\] and headache. Any = occurrence of the symptom regardless of intensity grade and relationship to the vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination.
Number of Subjects With Haematological and Biochemical Results by Maximum Grade	From Day 1 to Day 60	Parameters analysed were ALT, activated partial thromboplastin time \[APTT\], AST, total bilirubin \[TB\], CRE, EOS, haemoglobin decrease \[HgD\], LYM, NEU, platelets \[PLA\], PT, white blood cells decrease \[WBCD\] and white blood cells increase \[WBCI\]. Assessed grades were: Unknown \[UG\], grade 0 \[G0\] = no grade, 1 \[G1\] = mild grade, 2 \[G2\] = moderate grade, 3 \[G3\] = severe grade, 4 \[G4\] = potentially life threatening and overall grading \[GTotal\]. Parameter grade combinations expressed were: parameter plus UG/G0/1/2/3/4/Total at baseline versus grading G0/1/2/3/4/Total from Day 1 up to Day 60, for the same parameter, e.g. ALT G0-G2.
Number of Subjects With Serious Adverse Events (SAEs)	From Day 0 to Day 360	Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Solicited Local Symptoms	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. All solicited local symptoms are considered as related to the vaccination.
Number of Subjects With Unsolicited Adverse Events (AEs)	During the 30-day (Days 0-29) post-vaccination period	An unsolicited AE covers 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 out-side the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Number of Subjects With Haematological and Biochemical Laboratory Abnormalities	At Day 360	Haematological/Biochemical parameters assessed were haemoglobin level \[HgL\], red blood cell \[RBC\], white blood cell \[WBC\], lymphocyte \[LYM\], neutrophil \[NEU\], eosinophil \[EOS\], reticulocyte \[RET\], platelet count \[PLC\], haptoglobin \[Hpg\], prothrombin time \[PT\] and partial thromboplastin time \[PTT\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], creatinine \[CRE\], lactate dehydrogenase \[LDH\] and bilirubin direct or total \[BLD/BLT\].Values were: unknown at baseline and below at Day360(U-B), unknown at baseline and within at Day360(U-W), unknown at baseline and above at Day360(U-A), below at baseline and below at Day360(B-B), below at baseline and within at Day360(B-W),below at baseline and above at Day360(B-A), within at baseline and below at Day360(W-B),within at baseline and within at Day360(W-W), within at baseline and above at Day360(W-A),above at baseline and below at Day360(A-B),above at baseline and within at Day360(A-W),above at baseline and above at Day360(A-A).

Secondary Outcome Measures

Name	Time	Method
Anti-respiratory Syncytial Virus (RSV) Neutralizing Antibodies Titers	At pre-vaccination (Day 0), post-Dose 1 (Day 30) and post-Dose 2 (Day 60)	Serum neutralizing antibody titers were reported as the inverse of the serum dilution which yielded a 60% reduction in the number of viral plaques compared to virus control without serum (Estimated Dilution: ED60). Antibody titers were expressed as Geometric Mean Titers (GMTs).
Frequency of Anti-F Immunoglobulin g (IgG) and/or Immunoglobulin A (IgA) Antibody Secreting B-cells (ASC)	At pre-vaccination (Day 0) and post-Dose 1 (Day 7, Day 30) and post-Dose 2 (Day 37, Day 60)	IgG/IgA antibody specific B-cells/ expressed as B-cells per million cells, were determined by the ELISpot assay.
Number of Subjects With Haematological and Biochemical Results by Maximum Grade	From Day 1 up to Day 360	Parameters analysed were ALT, activated partial thromboplastin time \[APTT\], AST, total bilirubin \[TB\], CRE, EOS, haemoglobin decrease \[HgD\], LYM, NEU, platelets \[PLA\], PT, white blood cells decrease \[WBCD\] and white blood cells increase \[WBCI\]. Assessed grades were: Unknown \[UG\], grade 0 \[G0\] = no grade, 1 \[G1\] = mild grade, 2 \[G2\] = moderate grade, 3 \[G3\] = severe grade, 4 \[G4\] = potentially life threatening and overall grading \[GTotal\]. Parameter grade combinations expressed were: parameter plus UG/G0/1/2/3/4/Total at baseline versus grading G0/1/2/3/4/Total from Day 1 up to Day 360, for the same parameter, e.g. ALT G0-G2.
Number of Subjects With Anti-RSV Neutralizing Antibodies Above the Cut-off Value	At pre-vaccination (Day 0), post-Dose 1 (Day 30) and post-Dose 2 (Day 60)	Pre-defined cut-off values was higher than or equal to (≥) 8 ED60.
Frequency of RSV Viral Protein F, N, M2-1 Specific Interferon-gamma (IFN-γ) Secreting T-cells	At pre-vaccination (Day 0) and post-Dose 1 (Day 7, Day 30) and post-Dose 2 (Day 37, Day 60)	Interferon-gamma specific T-cells, expressed as T-cells per (/) million cells, were determined by the Enzyme Linked ImmunoSpot (ELISpot) assay.

Trial Locations

Locations (1)

GSK Investigational Site; 🇬🇧 Oxford, Oxfordshire, United Kingdom