A Study in Tanzania of a New Vaccine Against Two Types of Ebola

Study Overview
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Brief Summary
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An open label, first in human, non-randomised, dose escalation, single centre, phase Ib clinical trial

Detailed Description
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This is an open label, first in human, dose escalation, phase Ib clinical trial to assess the safety and immunogenicity of the candidate ChAdOx1 biEBOV vaccine in healthy Tanzanian volunteers aged 18-45. The vaccine will be administered intramuscularly (IM). There will be 4 study groups and it is anticipated that a total of 76 volunteers will be enrolled. Dose escalation and sentinel participant procedures will be implemented. Volunteers will be first recruited into Group 1 and subsequently into Groups 2 and 3 following interim clinical safety reviews. Volunteers will be sequentially allocated to a study group by selecting eligible volunteers for enrolment following screening. Sequential allocation will occur based on the order in which volunteers are enrolled. Group 4 will be recruited last, with dose selection being dependent on completion of groups 1-3 and a review of safety data. The trial is funded by Innovate UK project reference 971615.

Official Title
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A Phase Ib Study to Determine the Safety and Immunogenicity of a Bivalent ChAdOx1 Vectored Vaccine Against Zaire and Sudan Ebola Virus Species in Tanzanian Healthy Adult Volunteers

Conditions
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Ebola

Intervention / Treatment
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* Biological: ChAdOx1 biEBOV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults aged 18 to 45 years. Able and willing (in the Investigator's opinion) to comply with all study requirements. Agreement to release medical and other information concerning contra-indications for participation in the study, and to be attended by a study clinician for physical examination and any other clinical investigations. Agreement to refrain from blood donation while in the study. Able to read and write Provide written informed consent. For women of childbearing potential only: Willingness to practice continuous effective contraception for the duration of the trial For women of childbearing potential only: A negative pregnancy test on the day of both screening and vaccination. Long term (at least 6 months) or permanent residence in Bagamoyo district. Availability through mobile phone 24 hours a day during the whole study period Agreement to provide personal contact information and contact information of a third party household member or close friend to study team. Exclusion Criteria: Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment or during the trial follow up period. Receipt of a recombinant simian adenoviral vaccine prior to enrolment Planned receipt of another adenoviral vectored vaccine (e.g., Oxford/AstraZeneca or Janssen COVID-19 vaccines) within 90 days after the vaccination with the ChAdOx1 biEBOV Planned or actual receipt of any vaccines administered within 30 days (before or after) enrolment and/or planned receipt of a vaccine ≤30 days after enrolment EXCEPT for protein, RNA (or other non-adenovirus based) COVID-19 vaccinations which may be given within 14 days of the trial vaccine. Previous receipt of an Ebolavirus vaccine Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) systemically active immunosuppressant medication within the past 6 months. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. History of hereditary angioedema acquired angioedema, or idiopathic angioedema. History of anaphylaxis in relation to vaccination. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). History of serious psychiatric condition likely to affect participation in the study. Ongoing or planned pregnancy or breastfeeding during the trial follow up period Known history of bleeding disorder (e.g., Factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. History of confirmed major thrombotic event (including cerebral venous sinus thrombosis, deep vein thrombosis, pulmonary embolism), known history of antiphospholipid syndrome, or history of heparin induced thrombocytopenia. Any other serious chronic illness requiring hospital specialist supervision. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week. Suspected or known injecting drug abuse in the 5 years preceding enrolment. Detectable circulating hepatitis B surface antigen (HBsAg). Seropositive for hepatitis C virus (antibodies to HCV). Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis. Body mass index (BMI) of <18 or >30 Kg/m2 Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data. Acute disease at the time of administration of the IMP (acute disease is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhoea or mild upper respiratory infection without fever, i.e., axillary temperature < 37.5°C.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>n=6 participants vaccinated with a single dose of ChAdOx1 biEBOV 5×10^9 vp | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV is provided as a liquid in glass vials and administered intramuscularly into the deltoid of the non-dominant arm (preferably)<br>|
| Experimental: Group 2<br>n=6 participants vaccinated with a single dose of ChAdOx1 biEBOV 2.5×10^10 vp Note: The DSMB may recommend increasing the size of group 2 to n=9 in the event of higher than expected reactogenicity | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV is provided as a liquid in glass vials and administered intramuscularly into the deltoid of the non-dominant arm (preferably)<br>|
| Experimental: Group 3<br>n=11 participants vaccinated with a single dose of ChAdOx1 biEBOV 5×10^10 vp | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV is provided as a liquid in glass vials and administered intramuscularly into the deltoid of the non-dominant arm (preferably)<br>|
| Experimental: Group 4<br>n=25 participants vaccinated with a two doses of ChAdOx1 biEBOV at the final selected dose, based on safety data for groups1-3. The second dose is administered after 12 weeks. Note:The dose for group 4 will be selected following a review of safety data to 28 days post vaccination for all previous participants (groups 1 to 3 | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV is provided as a liquid in glass vials and administered intramuscularly into the deltoid of the non-dominant arm (preferably)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers. | Occurrence of solicited local reactogenicity signs and symptoms | 7 days following vaccination | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers. | Occurrence of solicited systemic reactogenicity signs and symptoms | 7 days following vaccination | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers. | Occurrence of unsolicited adverse events (AEs) | 28 days following vaccination | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers. | Occurrence of changes from baseline for safety laboratory measures | Days 0, 2, 7, 28 | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers. | Occurrence of SAEs and AESIs | Whole duration of the study ( 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the immunogenicity of ChAdOx1 biEBOV in healthy adult volunteers. | Filovirus GP specific serological response as measured by ELISA | Days 0, 28, 56, 182 | 
| Investigate the immunogenicity of ChAdOx1 biEBOV in healthy adult volunteers. | Filovirus GP specific T cell response measured by IFN-γ ELISPOT | Days 0, 7, 14, 28, 56, 128 |