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

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 Children in Africa

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02548078
• Other study ID #: 202090
• Secondary ID: 2014-004714-28
• Status: Completed
• Phase: Phase 2
• Start date: November 9, 2015
• Est. completion date: May 15, 2017

Study information

• Verified date: March 2018
• 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 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: May 15, 2017
• Est. primary completion date: May 15, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year to 17 Years

Eligibility

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.

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 administered intramuscular
• Nimenrix powder and solvent for solution for injection in pre-filled syringe; Meningococcal group A, C, W-135 and Y conjugate vaccine
A single dose administered intramuscular

Locations

Country	Name	City	State
Mali	GSK Investigational Site	Bamako
Senegal	GSK Investigational Site	Dakar

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Mali,  Senegal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Subjects With Solicited Local Symptoms, Overall	Assessed solicited local symptoms included: pain and swelling at the injections site. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = crying at limb movement/spontaneous pain.Grade 3 swelling = swelling extending on a surface higher than (>) 30 millimeters (mm). Solicited local symptoms, for this endpoint, were assessed in all subjects, in both groups.	During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
Primary	Number of Subjects With Solicited Local Symptoms, by Age Stratum	Assessed solicited local symptoms included: pain and swelling at the injections site. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = crying at limb movement/spontaneous pain.Grade 3 swelling = swelling extending on a surface higher than (>) 30 millimeters (mm), for children between 1-5 years old; > 50 mm for children between 6-12 years old and >100 mm for children between 13-17 years old.	During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
Primary	Number of Subjects With Solicited General Symptoms, Overall	Solicited general symptoms assessed included: fatigue, fever [defined as axillary temperature equal to or above (=) 37.5 degrees Celsius (°C)], gastrointestinal symptoms [nausea, vomiting, diarrhoea and/or abdominal pain], headache, drowsiness, irritability/fussiness and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 fatigue/headache/drowsiness/gastrointestinal symptoms = fatigue/headache/drowsiness/gastrointestinal symptoms that prevented normal activity. Grade 3 fever = temperature > 39.5°C. Grade 3 irritability/fussiness = crying that couldn't be comforted. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination. Solicited general symptoms, for this endpoint, were assessed in all subjects, in both groups.	During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
Primary	Number of Subjects With Solicited General Symptoms, by Age Stratum	Solicited general symptoms assessed included: fatigue, fever [defined as axillary temperature equal to or above (=) 37.5 degrees Celsius (°C)], gastrointestinal symptoms [nausea, vomiting, diarrhoea and/or abdominal pain], headache, drowsiness, irritability/fussiness and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 fatigue/headache/drowsiness/gastrointestinal symptoms = fatigue/headache/drowsiness/gastrointestinal symptoms that prevented normal activity. Grade 3 fever = temperature > 39.5°C. Grade 3 irritability/fussiness = crying that couldn't be comforted. Grade 3 loss of appetite = not eating at all. Related = symptom assessed by the investigator as related to the vaccination. Solicited general symptoms, for this endpoint, were assessed in subjects aged 1-5 years, 6-12 years and 13-17 years. Symptoms with no values were not assessed for those specific age groups.	During a 7-day follow-up period after each vaccination (i.e. the day of vaccination and 6 subsequent days)
Primary	Number of Subjects With Unsolicited Adverse Events (AEs), Overall	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 outside 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. Unsolicited adverse events, for this endpoint, were assessed in all subjects, in both groups.	During the 30-day follow-up period after each vaccination (i.e. the day of vaccination and 29 subsequent days)
Primary	Number of Subjects With Unsolicited Adverse Events (AEs), by Age Stratum	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 outside 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. Unsolicited AEs, for this endpoint, were assessed in subjects between 1-5 years of age, 6-12 years of age and 13-17 years of age.	During the 30-day follow-up period after each vaccination (i.e. the day of vaccination and 29 subsequent days)
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Screening.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Screening
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Day 3.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Day 3
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Day 6.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Day 6
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Day 30.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Day 30
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 6.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 6
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 6 + 6 Days.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 6 + 6 Days
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 6 + 30 Days.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 6 + 30 Days
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, Overall	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 for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 12.
Primary	Percentage of Subjects With Haematological Laboratory Abnormalities, by Age Stratum	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 for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 12
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Screening.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Screening
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Day 3.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Day 3
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Day 6.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Day 6
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Day 30.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Day 30
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 6.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 6
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 6 + 6 Days.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 6 + 6 Days
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 6 + 30 Days.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 6 + 30 Days
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, Overall	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for all subjects, in both groups. Reference range indicators used were: high, low, normal.	At Month 12.
Primary	Percentage of Subjects With Biochemical Laboratory Abnormalities, by Age Stratum	Biochemical parameters assessed included: alanine aminotransferase [ALT], creatinine [CRE] for subjects aged 1-5 years, 6-12 years and 13-17 years. Reference range indicators used were: high, low, normal.	At Month 12
Primary	Number of Subjects With Adverse Events of Specific Interest (AESI), Overall	AESI included clinical symptoms of thrombocytopenia for all subjects, in both groups.	During the 7 day follow-up period after vaccination at Day 0 (i.e., Day 0 up to Day 6)
Primary	Number of Subjects With Adverse Events of Specific Interest (AESI), by Age Stratum	AESI included clinical symptoms of thrombocytopenia for subjects aged 1-5 years, 6-12 years and 13-17 years.	During the 7 day follow-up period after vaccination at Day 0 (i.e. Day 0 up to Day 6)
Primary	Number of Subjects With Serious Adverse Events, Overall	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. SAEs, for this endpoint, were assessed in all subjects, in both groups.	During the entire study period: From Screening to Month 12
Primary	Number of Subjects With Serious Adverse Events, by Age Stratum	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. SAEs, for this endpoint, were assessed in subjects aged 1-5 years, 6-12 years and 13-17 years.	During the entire study period: From Screening to Month 12
Secondary	Anti-glycoprotein (GP) Ebola Virus Zaire (EBOV) Antibody Titers, Overall	Anti-GP EBOV antibodies were expressed as Geometric Mean Titers (GMTs), as measured by the Enzyme-Linked Immunosorbent Assay (ELISA) and assessed in all subjects, in both groups.	At Day 0, Day 30, Month 6, Month 6 + 30 Days and Month 12.
Secondary	Anti-GP EBOV Antibody Titers, by Age Stratum	Anti-GP EBOV antibodies were expressed as Geometric Mean Titers (GMTs), as measured by the Enzyme-Linked Immunosorbent Assay (ELISA) and assessed in subjects aged 1-5 years, 6-12 years and 13-17 years.	At Day 0, Day 30, Month 6, Month 6 + 30 Days and Month 12
Secondary	Percentage of Seronegative/Seropositive Subjects for Anti-GP EBOV Antibodies, Overall	A seronegative subject is a subject whose titer is below the cut-off value. A seropositive subject is a subject whose titer is greater than or equal to the cut-off value. The analysis, for this endpoint, was performed on all subjects, in both groups.	At Day 0, Day 30, Month 6 and Month 6 + 30 Days.
Secondary	Percentage of Seronegative/Seropositive Subjects for Anti-GP EBOV Antibodies, by Age Stratum	A seronegative subject is a subject whose titer is below the cut-off value. A seropositive subject is a subject whose titer is greater than or equal to the cut-off value. The analysis, for this endpoint, was performed on subjects aged 1-5 years, 6-12 years and 13-17 years.	At Day 0, Day 30, Month 6 and Month 6 + 30 Days