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

• ClinicalTrials.gov Identifier: NCT02485301
• Recruitment Status: Completed
• First Posted: June 30, 2015
• Results First Posted: January 4, 2018
• Last Update Posted: January 4, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Virus Diseases	Biological: GlaxoSmithKline (GSK) Biologicals' investigational recombinant chimpanzee adenovirus Type 3-vectored Ebola Zaire vaccine (ChAd3-EBO-Z) (GSK3390107A); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3024 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity Study of GSK Biologicals' Investigational Recombinant Chimpanzee Adenovirus Type 3-vectored Ebola Zaire Vaccine (GSK3390107A) in Adults in Africa
• Actual Study Start Date: July 15, 2015
• Actual Primary Completion Date: December 23, 2016
• Actual Study Completion Date: December 23, 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group EBO-Z; The subjects in the Group EBO-Z will receive the vaccine at Day 0 of the study	Biological: GlaxoSmithKline (GSK) Biologicals' investigational recombinant chimpanzee adenovirus Type 3-vectored Ebola Zaire vaccine (ChAd3-EBO-Z) (GSK3390107A); A single dose administrated intramuscular
Placebo Comparator: Group Placebo/ EBO-Z; 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	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

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Solicited Local Adverse Events [ Time Frame: During the 7-Day (Days 0-6) post-vaccination period ]
   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.
2. Number of Subjects With Solicited General Adverse Events [ Time Frame: During the 7-Day (Days 0-6) post-vaccination period ]
   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.
3. Number of Subjects With Unsolicited Adverse Events (AEs) [ Time Frame: 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.
4. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Screening ]
   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.
5. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Day 3 ]
   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.
6. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Day 6 ]
   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.
7. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Day 30 ]
   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.
8. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Month 6 ]
   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.
9. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Month 6 + 6 Days ]
   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.
10. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Month 6 + 30 Days ]
    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.
11. Percentage of Subjects With Haematological Laboratory Abnormalities [ Time Frame: At Month 12 ]
    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.
12. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Screening ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
13. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Day 3 ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
14. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Day 6 ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
15. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Day 30 ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
16. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Month 6 ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
17. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Month 6 + 6 Days ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
18. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Month 6 + 30 Days ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
19. Percentage of Subjects With Biochemical Laboratory Abnormalities [ Time Frame: At Month 12 ]
    Biochemical parameters assessed included: aminotransferase and creatinine. Reference range indicators used were: high, low, normal.
20. Number of Subjects With Adverse Events of Specific Interest (AESI) [ Time Frame: During the 7-Day (Days 0-6) post-vaccination period ]
    AESI included clinical symptoms of thrombocytopenia.
21. Number of Subjects With Serious Adverse Events (SAEs) [ Time Frame: During the entire study period (up to Month 12) ]
    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.

Secondary Outcome Measures :

1. Concentrations of Anti-glycoprotein Ebola Zaire Virus (Anti-GP EBOV) [ Time Frame: At Day 0, Day 30, Month 6 and Month 12 ]
   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).
2. Percentage of Seronegative/Seropositive Subjects for Anti-GP EBOV Antibodies [ Time Frame: At Day 0, Day 30, Month 6 and Month 12 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Cameroon

GSK Investigational Site

Bamenda, Cameroon

GSK Investigational Site

Yaounde, Cameroon

Mali

GSK Investigational Site

Bamako, Mali

Nigeria

GSK Investigational Site

Abuja, Nigeria

Senegal

GSK Investigational Site

Dakar, Senegal

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tapia MD, Sow SO, Ndiaye BP, Mbaye KD, Thiongane A, Ndour CT, Mboup S, Ake JA, Keshinro B, Akintunde GA, Kinge TN, Vernet G, Bigna JJ, Oguche S, Koram KA, Asante KP, Hogrefe WR, Gunther S, Naficy A, De Ryck I, Debois M, Bourguignon P, Jongert E, Ballou WR, Koutsoukos M, Roman F; Zaire EBola Research Alliance group. Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2020 Jun;20(6):707-718. doi: 10.1016/S1473-3099(20)30016-5. Epub 2020 Mar 19.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02485301
• Other Study ID Numbers: 202091
• First Posted: June 30, 2015
• Results First Posted: January 4, 2018
• Last Update Posted: January 4, 2018
• Last Verified: November 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

Protection against Ebola Zaire virus

Additional relevant MeSH terms:

Virus Diseases; Infections