Clinical trial NCT02548078: A Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Children
Official title: Safety and Immunogenicity Study of GSK Biologicals' Investigational Recombinant Chimpanzee Adenovirus Type 3-vectored Ebola Zaire Vaccine (GSK3390107A) in Children in Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Virus Diseases
Keywords: Protection against Ebola Zaire virus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2015-09-14
Enrollment: 600
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to assess the safety and reactogenicity of a single IM dose of the GSK3390107A (ChAd3 EBO-Z) vaccine, overall and in children aged 1 to 5, 6 to 12, and 13 to 17 years, separately.

Considering the risk of exposure to Ebola and the potential (based on animal data) for the investigational GSK3390107A (ChAd3-EBO-Z) vaccine to afford at least partial protection, all children in the study will receive the investigational GSK3390107A (ChAd3 EBO-Z) vaccine. The children in the Group GSK3390107A+Nimenrix will receive the investigational GSK3390107A (ChAd3-EBO-Z) vaccine at Day 0 of the study, whereas the children in the Group Nimenrix+GSK3390107A will receive Nimenrix at Day 0 (as a control). At Month 6, the children in the Group Nimenrix+GSK3390107A will receive the investigational GSK3390107A (ChAd3-EBO-Z) vaccine (provided that no safety concerns are raised), whereas the children in the Group GSK3390107A+Nimenrix will receive Nimenrix.


Eligibility criteria: Inclusion Criteria:

* Subject's parent(s)/ legally acceptable representative(s) (LAR\[s\]) who, in the opinion of the Investigator, can and will comply with the requirements of the protocol (e.g. 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' parent(s)/ LAR\[s\] prior to performing any study specific procedure. In addition, written/ thumb printed in-formed assent should be obtained if appropriate (from all subjects aged 13 to 17 years and from younger subjects as per local requirements).
* A male or female child aged 1 to 17 years inclusive at the time of Screening.
* Subjects with a negative RDT test for Malaria within 30 days prior to randomisation into the study.

OR Subjects with a positive RDT test for Malaria who completed antimalarial treatment at least 5 days prior to randomisation into the study.

* Healthy subjects as per Investigator judgement, as estab-lished by medical history, clinical examination and haema-tology/ biochemistry laboratory parameters screening be-fore entering into the study.
* Female subjects of non-childbearing potential may be enrolled in the study.

  * Non-childbearing potential is defined as pre-menarche or ovariectomy.
* 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:

* Child in care.
* 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 chim-panzee adenoviral vectored investigational vaccine.
* Known prior EBOV or SUDV disease.
* Travel to country affected by the EBOV epidemic or direct contact with person with EVD within 21 days prior to the Day 0 visit.
* History of any reaction or hypersensitivity (such as ana-phylaxis, urticaria (hives), respiratory difficulty, angioe-dema, 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.
* Acute or chronic illness determined by medical history, clinical examination and laboratory screening tests in-cluding, but not limited to:
* Clinically significant immunosuppressive or immunodeficient condition (e.g. clinical acquired immune deficiency syndrome \[AIDS\]).
* Major congenital defects.
* Malnutrition (defined as weight for age Z-score less than -3, or other clinical signs of malnutrition).
* Any clinically significant haematological or biochemical laboratory abnormality.
* Pregnant female.
* Any condition that in the Investigator's opinion may po-tentially compromise subject safety or interfere with sub-ject assessment or compliance.

Primary outcomes:
measure: Number of Subjects With Solicited Local Symptoms, Overall
timeFrame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of Subjects With Solicited Local Symptoms, by Age Stratum
timeFrame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of Subjects With Solicited General Symptoms, Overall
timeFrame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of Subjects With Solicited General Symptoms, by Age Stratum
timeFrame: During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
measure: Number of Subjects With Unsolicited Adverse Events (AEs), Overall
timeFrame: During the 30-day follow-up period after each vaccination (i.e. the day of vaccination and 29 subsequent days)
measure: Number of Subjects With Unsolicited Adverse Events (AEs), by Age Stratum
timeFrame: During the 30-day follow-up period after each vaccination (i.e. the day of vaccination and 29 subsequent days)
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Screening.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Screening
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Day 3.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Day 3
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Day 6.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Day 6
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Day 30.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Day 30
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Month 6.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 6
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Month 6 + 6 Days.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 6 + 6 Days
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Month 6 + 30 Days.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 6 + 30 Days
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, Overall
timeFrame: At Month 12.
measure: Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 12
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Screening.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Screening
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Day 3.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Day 3
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Day 6.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Day 6
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Day 30.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Day 30
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Month 6.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 6
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Month 6 + 6 Days.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 6 + 6 Days
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Month 6 + 30 Days.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 6 + 30 Days
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall
timeFrame: At Month 12.
measure: Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum
timeFrame: At Month 12
measure: Number of Subjects With Adverse Events of Specific Interest (AESI), Overall
timeFrame: During the 7 day follow-up period after vaccination at Day 0 (i.e., Day 0 up to Day 6)
measure: Number of Subjects With Adverse Events of Specific Interest (AESI), by Age Stratum
timeFrame: During the 7 day follow-up period after vaccination at Day 0 (i.e. Day 0 up to Day 6)
measure: Number of Subjects With Serious Adverse Events, Overall
timeFrame: During the entire study period: From Screening to Month 12
measure: Number of Subjects With Serious Adverse Events, by Age Stratum
timeFrame: During the entire study period: From Screening to Month 12
Secondary outcomes:
measure: Anti-glycoprotein (GP) Ebola Virus Zaire (EBOV) Antibody Titers, Overall
timeFrame: At Day 0, Day 30, Month 6, Month 6 + 30 Days and Month 12.
measure: Anti-GP EBOV Antibody Titers, by Age Stratum
timeFrame: At Day 0, Day 30, Month 6, Month 6 + 30 Days and Month 12
measure: Percentage of Seronegative/Seropositive Subjects for Anti-GP EBOV Antibodies, Overall
timeFrame: At Day 0, Day 30, Month 6 and Month 6 + 30 Days.
measure: Percentage of Seronegative/Seropositive Subjects for Anti-GP EBOV Antibodies, by Age Stratum
timeFrame: At Day 0, Day 30, Month 6 and Month 6 + 30 Days
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: GSK Investigational Site
city: Dakar
country: Senegal
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tapia MD, Sow SO, Mbaye KD, Thiongane A, Ndiaye BP, Ndour CT, Mboup S, Keshinro B, Kinge TN, Vernet G, Bigna JJ, Oguche S, Koram KA, Asante KP, Gobert P, Hogrefe WR, 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 children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2020 Jun;20(6):719-730. doi: 10.1016/S1473-3099(20)30019-0. Epub 2020 Mar 19.