A Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Adults

Virus Diseases Clinical Trial

Official title:

Safety and Immunogenicity Study of GSK Biologicals' Investigational Recombinant Chimpanzee Adenovirus Type 3-vectored Ebola Zaire Vaccine (GSK3390107A) in Adults in Africa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02485301
• Other study ID #: 202091
• Status: Completed
• Phase: Phase 2
• First received: June 18, 2015
• Last updated: December 4, 2017
• Start date: July 15, 2015
• Est. completion date: December 23, 2016

Study information

• Verified date: November 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety and immunogenicity of the investigational ChAd3-EBO-Z vaccine administered to approximately 3 000 adults in Africa as a single IM dose Considering the risk of exposure to Ebola and the potential (based on animal data) for the investigational ChAd3-EBO-Z vaccine to afford at least partial protection, all subjects in the study will receive the investigational ChAd3-EBO-Z vaccine. The subjects in the Group EBO-Z will receive the vaccine at Day 0 of the study, whereas the subjects in the Group Placebo/ EBO-Z will receive a placebo at Day 0 (as a control) and will receive the investigational ChAd3-EBO-Z vaccine at Month 6, provided that no safety concerns are raised. In addition, vaccinating all subjects in the study with the investigational ChAd3 EBO Z vaccine will allow an increase of the safety database of the investigational vaccine. In case the geographic range of Ebola virus Zaire (EBOV) transmission expands to encompass any of the regions where this trial is conducted, earlier administration of the investigational ChAd3-EBO-Z vaccine to the subjects in the Group Placebo/ EBO-Z will be considered in that region.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3024
• Est. completion date: December 23, 2016
• Est. primary completion date: December 23, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects who, in the opinion of the Investigator, can and will comply with the requirements of the protocol (e.g. capability of or availability for Diary Card completion, return for follow-up visits, availability for clinical follow-up throughout the study period).

• Written/ thumb printed informed consent obtained from the subject prior to performing any study specific procedure or written/ thumb printed informed consent obtained from the subject's parent(s)/ legally acceptable representative(s) (LAR[s]) and written/ thumb printed informed assent obtained from the subject, for minor subjects. This will only be applicable for countries where the legal age of majority is = 21 years.

• A male or female aged 18 years of age or older at the time of Screening.

• Healthy subjects as per Investigator judgement, as established by medical history, clinical examination and haematology/ biochemistry laboratory parameters screening before entering into the study.

• Female subjects of non-childbearing potential may be enrolled in the study.

• Non-childbearing potential is defined as pre-menarche, current tubal ligation, 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 the Day 0 visit, and

• has a negative pregnancy test at the Day 0 visit, and

• has agreed to continue adequate contraception until 30 days after the Month 6 visit.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the Day 0 visit, or planned use during the study period.

• Previous vaccination with an investigational EBOV or Marburg vaccine, or previous vaccination with a chimpanzee adenoviral vectored investigational vaccine.

• Known prior EBOV or SUDV disease.

• Travel to a country affected by the EBOV epidemic or direct contact with a person with EVD within 21 days prior to the Day 0 visit.

• History of any reaction or hypersensitivity (such as anaphylaxis, urticaria [hives], respiratory difficulty, angioedema, or abdominal pain) likely to be exacerbated by any component of the study vaccine.

• Planned administration/ administration of a vaccine not foreseen by the study protocol in the period starting 30 days before and ending 30 days after each vaccination visit.

• Serious acute or chronic illness determined by medical history and clinical examination including, but not limited to:

• Clinically significant immunosuppressive or immunodeficient condition (e.g. clinical acquired immune deficiency syndrome [AIDS]).

• Any clinically significant haematological (CBC, including differential count and platelet count) or biochemical (ALT, creatinine) laboratory abnormality.

• Any chronic illness with recent signs of exacerbation, or imposing a change in the chronic treatment regimen, within 3 months prior to the Day 0 visit.

• Any unstable chronic medical condition (e.g. uncontrolled asthma).

• Pregnant female.

Related Conditions & MeSH terms

• Virus Diseases

Intervention

Biological:
• GlaxoSmithKline (GSK) Biologicals' investigational recombinant chimpanzee adenovirus Type 3-vectored Ebola Zaire vaccine (ChAd3-EBO-Z) (GSK3390107A)
A single dose administrated intramuscular

Drug:
• Placebo
A single dose administrated intramuscular

Locations

Country	Name	City	State
Cameroon	GSK Investigational Site	Bamenda
Cameroon	GSK Investigational Site	Yaounde
Mali	GSK Investigational Site	Bamako
Nigeria	GSK Investigational Site	Abuja
Senegal	GSK Investigational Site	Dakar

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Cameroon,  Mali,  Nigeria,  Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Solicited Local Adverse Events	Assessed solicited local adverse events were pain, redness and swelling. Any = occurrence of any solicited local adverse event regardless of their intensity grade. Grade 3 Pain = significant pain at rest. Prevented normal every day activities. Grade 3 Redness/Swelling = redness/swelling spreading beyond 100 millimeters (mm) from injection site.	During the 7-Day (Days 0-6) post-vaccination period
Primary	Number of Subjects With Solicited General Adverse Events	Assessed solicited general adverse events were fatigue, fever [defined as axillary temperature higher than or equal to (=) 37.5 degrees Celsius (°C)], gastrointestinal (gastro) adverse events [nausea, vomiting, diarrhoea and/or abdominal pain] and headache. Any = occurrence of any general adverse events regardless of intensity grade or relationship to vaccination. Grade 3 fatigue, gastrointestinal symptoms and headache = adverse event that prevented normal activities. Grade 3 fever = fever = 39.5 °C. Related = adverse event assessed by the investigator as related to the vaccination.	During the 7-Day (Days 0-6) post-vaccination period
Primary	Number of Subjects With Unsolicited Adverse Events (AEs)	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.	During the 30-Day (Days 0-29) post-vaccination period
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Screening
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Day 3
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Day 6
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Day 30
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Month 6
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Month 6 + 6 Days
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Month 6 + 30 Days
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities	Haematological parameters assessed included: complete blood count (red blood cells [RBC], neutrophils, lymphocytes, white blood cells [WBC], haemoglobin), as well as differential count and platelet count. Reference range indicators used were: high, low, normal.	At Month 12
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Screening
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Day 3
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Day 6
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Day 30
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Month 6
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Month 6 + 6 Days
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Month 6 + 30 Days
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities	Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.	At Month 12
Primary	Number of Subjects With Adverse Events of Specific Interest (AESI)	AESI included clinical symptoms of thrombocytopenia.	During the 7-Day (Days 0-6) post-vaccination period
Primary	Number of Subjects With Serious Adverse Events (SAEs)	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.	During the entire study period (up to Month 12)
Secondary	Concentrations of Anti-glycoprotein Ebola Zaire Virus (Anti-GP EBOV)	Anti-GP EBOV antibody concentrations were measured by Enzyme-Linked Immunosorbent Assay (ELISA), presented as geometric mean concentrations (GMC), and expressed in ELISA units per milliliter (EU/mL).	At Day 0, Day 30, Month 6 and Month 12
Secondary	Percentage of Seronegative/Seropositive Subjects for Anti-GP EBOV Antibodies	A seronegative subject (S-) is a subject whose titer is below (<) 36.11 EU/mL. A seropositive subject (S+) is a subject whose titer is greater than or equal to (=) 36.11 EU/mL.	At Day 0, Day 30, Month 6 and Month 12