A Study of a New Vaccine Against Two Types of Ebola

Study Overview
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Brief Summary
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An open-label, non-randomised, dose escalation, first-in-human, single centre, phase I clinical trial to determine the safety and immunogenicity of a bivalent ChAdOx1 vectored vaccine against Zaire and Sudan Ebola virus species in healthy adult volunteers.

Detailed Description
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This is a first-in-human, open-label, dose escalation, phase I clinical trial to assess the safety and immunogenicity of the candidate ChAdOx1 biEBOV vaccine in healthy UK volunteers aged 18-55. The vaccine will be administered intramuscularly (IM). Volunteers will be recruited and vaccinated at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Oxford. There will be 3 study groups and it is anticipated that a total of 26 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.

Official Title
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A Phase I Study to Determine the Safety and Immunogenicity of a Bivalent ChAdOx1 Vectored Vaccine Against Zaire and Sudan Ebola Virus Species in UK 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 55 years. Able and willing (in the Investigator's opinion) to comply with all study requirements. Willing to allow confirmation of their past medical history either through: provision of a GP medical record summary, allowing investigators to obtain a copy of their medical history from their GP practice or by providing an alternative acceptable means of confirming their past medical history. Agreement to refrain from blood donation during the course of the study. 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. 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. Including hypersensitivity to the active substance or to any of the excipients of the IMP or Vaxzevria (i.e. the Oxford/AstraZeneca COVID-19 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. Bleeding disorder (eg. 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), history of antiphospholipid syndrome, or history of heparin induced thrombocytopenia. Individuals who have experienced thrombosis with thrombocytopenia syndrome (TTS) following vaccination with Vaxzevria (i.e. the Oxford/AstraZeneca COVID-19 vaccine). Individuals who have previously experienced episodes of capillary leak syndrome. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Low Dose<br>n=6 participants vaccinated with a single dose of ChAdOx1 biEBOV 5x10^9 vp | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV provided as a liquid in glass vials and administered intramuscularly into the deltoid of the non-dominant arm (preferably)<br>|
| Experimental: Group 2: Mid Dose<br>n=6 participants vaccinated with a single dose of ChAdOx1 biEBOV 2.5x10^10 vp Note: may be increased to n=9 following interim safety reviews | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV provided as a liquid in glass vials and administered intramuscularly into the deltoid of the non-dominant arm (preferably)<br>|
| Experimental: Group 3: High Dose<br>n=14 participants vaccinated with two doses of ChAdOx1 biEBOV 5x10^10 vp, twelve weeks apart Note: will be decreased to n=11 if Group 2 is increased to n=9 | Biological: ChAdOx1 biEBOV<br>* ChAdOx1 biEBOV 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 signs and symptoms | Occurrence of solicited local and systemic reactogenicity signs and symptoms | 7 days following vaccination | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers: Occurrence of unsolicited signs and symptoms | Occurrence of unsolicited adverse events (AEs) | 28 days following vaccination | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers: Occurrence of Serious Adverse Events | Occurrence of SAEs and AESIs | Duration of the study (6 months) | 
| Investigate the safety and tolerability of ChAdOx1 biEBOV in healthy volunteers: Occurrence of adverse events as identified by change in baseline safety laboratory measures | Occurrence of changes from baseline safety laboratory measures (haematology and biochemistry) Safety laboratory measures include clinical blood tests for full blood count, liver function and renal function as graded on a predetermined toxicity grading scale. | 28 days following vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigate the immunogenicity of ChAdOx1 biEBOV in healthy adult volunteers: Measure of humoral immunogenicity | ELISA to quantify antibodies to filovirus glycoprotein (specific serological response) | At day 0, 28, 56 and 182 | 
| Investigate the immunogenicity of ChAdOx1 biEBOV in healthy adult volunteers: Measure of Cellular Immunogenicity | IFN-y ELISPOT to quantify filovirus glycoprotein specific T cell response | At day 0. 7. 14. 28. 56 and 182 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ebola Virus Disease, Zaire Ebolavirus, EBOV, Sudan Ebolavirus, SUDV, Vaccine