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A Study to Assess the New Candidate Rift Valley Fever Virus Vaccine in Healthy Adults

Primary Purpose

RVF, Rift Valley Fever

Status
Completed
Phase
Phase 1
Locations
Uganda
Study Type
Interventional
Intervention
ChAdOx1 RVF
Saline
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for RVF focused on measuring Rift Valley Fever, Vaccine, ChAdOx1

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

The volunteer must satisfy all the following criteria to be eligible for the study:

  1. Male and female healthy adults aged 18 to 50 years
  2. Able and willing to provide written informed consent
  3. Able and willing (in the Investigator's opinion) to comply with all study requirements
  4. For females only, willingness to practice continuous effective contraception during the study.
  5. Females of childbearing potential must have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test immediately prior to study vaccine administration
  6. Agreement to refrain from blood donation during the course of the study
  7. Healthy in the investigator's clinical judgement basing on the medical history and physical examination performed at screening
  8. Healthy on the basis of clinical laboratory tests (within the institutional normal laboratory reference ranges) performed at screening.
  9. Willing to provide verifiable identification to the study team
  10. Volunteer must have a means to be contacted or be willing to provide locator information to the study team
  11. Volunteer must pass the Test of Understanding (TOU)

Exclusion Criteria:

The volunteer may not enter the study if any of the following apply:

  1. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
  2. Prior receipt of an investigational vaccine as it may impact on interpretation of the trial data.
  3. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
  4. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
  5. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
  6. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
  7. Any history of anaphylaxis in relation to vaccination
  8. Pregnancy, lactation or willingness/intention to become pregnant during the study
  9. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  10. History of serious psychiatric condition likely to affect participation in the study
  11. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture
  12. Acute illness or temperature ≥37.5°C/99.5°F on the day of vaccination. Volunteer may be rescheduled for enrolment at a later date.
  13. Major surgery (per the investigator's judgement) within 4 weeks prior to screening or planned major surgery through the course of the study
  14. Any other serious chronic illness requiring hospital specialist supervision
  15. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 14 units every week
  16. Suspected or known injecting drug abuse in the 5 years preceding enrolment
  17. Seropositive for hepatitis B surface antigen (HBsAg)
  18. Seropositive for hepatitis C virus (antibodies to HCV)
  19. Any clinically significant abnormal finding on screening biochemistry, haematology and coagulation blood tests or urinalysis
  20. 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
  21. Prior natural exposure to RVFV as determined by seropositivity for RVFV antigens by ELISA.

Sites / Locations

  • MRC/UVRI and LSHTM Uganda Research Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Experimental

Arm Label

ChAdOx1 RVF group 1

Control group

ChAdOx1 RVF group 2

ChAdOx1 RVF group 3

Arm Description

Participants will receive ChAdOx1 RVF 5 x 10^9 vp, delivered intramuscularly

Placebo (Normal Saline), 0.5ml delivered intramuscularly

Participants will receive ChAdOx1 RVF 2.5 x 10^10 vp, delivered intramuscularly

Participants will receive ChAdOx1 RVF 5 x 10^10 vp, delivered intramuscularly

Outcomes

Primary Outcome Measures

Assess the safety profile of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: AE
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination, occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination, occurrence of unsolicited adverse events for 28 days following the vaccination, and occurrence of serious adverse events during the whole study duration
Assess the safety profile of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: change in baseline: AE
Change from baseline for safety laboratory measures: clinical blood test adverse events (full blood count, liver function tests and renal function) graded on a scaled adapted from the FDA healthy volunteer vaccine scale

Secondary Outcome Measures

Assess the immunogenicity of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: GnGc protein antibodies
Measures of immunogenicity to the ChAdOx1 RVF vaccine: * ELISA to quantify antibodies to GnGc proteins
Assess the immunogenicity of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: RVFV neutralising antibodies
Measures of immunogenicity to the ChAdOx1 RVF vaccine: * RVFV neutralising antibody titres
Assess the immunogenicity of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: ELISpot & flow cytometry
Measures of immunogenicity to the ChAdOx1 RVF vaccine: * Ex vivo ELISpot and flow cytometry responses to GnGc

Full Information

First Posted
October 19, 2020
Last Updated
February 3, 2023
Sponsor
University of Oxford
Collaborators
MRC/UVRI and LSHTM Uganda Research Unit
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1. Study Identification

Unique Protocol Identification Number
NCT04672824
Brief Title
A Study to Assess the New Candidate Rift Valley Fever Virus Vaccine in Healthy Adults
Official Title
A Phase I Study to Determine the Safety and Immunogenicity of the Candidate Rift Valley Fever Virus (RVFV) Vaccine ChAdOx1 RVF Among Healthy Adult Volunteers in Uganda
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
May 31, 2022 (Actual)
Primary Completion Date
December 15, 2022 (Actual)
Study Completion Date
December 15, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford
Collaborators
MRC/UVRI and LSHTM Uganda Research Unit

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Randomised, single blind, placebo - controlled, dose-escalation, phase I clinical trial recruiting healthy adults aged 18-50 years
Detailed Description
This is a randomised, single blind, placebo-controlled, dose escalation, phase I clinical trial to assess the safety and immunogenicity of the candidate ChAdOx1 RVF vaccine in healthy Ugandan volunteers aged 18-50. The vaccine will be administered intramuscularly. This study will run concurrently with the first-in-human ChAdOx1 RVF trial in Oxford. Vaccination at the MRC/UVRI and LSHTM Uganda Research Unit, Masaka will only begin upon receiving a favourable opinion of Uganda's trial DSMB of the 7-day post-vaccination safety analysis of the first two lowest dose groups (ChAdOx1 RVF 5 x 10^9vp and ChAdOx1 RVF 2.5 x 10^10vp) of the trial in Oxford. Volunteers will be recruited and vaccinated at the MRC/UVRI and LSHTM Uganda Research Unit Clinical Research Centre in Masaka. There will be three study groups and a total of 30 volunteers will be enrolled (table 3). Volunteers will be recruited sequentially into Groups 1,2 and 3. Within each group, eligible volunteers will be randomly allocated to receive either ChAdOx1 RVF or placebo of 0.9% Normal Saline in a ratio of 2:1 in group 1 and 5:1 in groups 2 and 3. The DSMB will analyse the 7-day post-vaccination safety data in each group and advise on whether to proceed to the next group with a higher dose .

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
RVF, Rift Valley Fever
Keywords
Rift Valley Fever, Vaccine, ChAdOx1

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
Participant
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ChAdOx1 RVF group 1
Arm Type
Experimental
Arm Description
Participants will receive ChAdOx1 RVF 5 x 10^9 vp, delivered intramuscularly
Arm Title
Control group
Arm Type
Active Comparator
Arm Description
Placebo (Normal Saline), 0.5ml delivered intramuscularly
Arm Title
ChAdOx1 RVF group 2
Arm Type
Experimental
Arm Description
Participants will receive ChAdOx1 RVF 2.5 x 10^10 vp, delivered intramuscularly
Arm Title
ChAdOx1 RVF group 3
Arm Type
Experimental
Arm Description
Participants will receive ChAdOx1 RVF 5 x 10^10 vp, delivered intramuscularly
Intervention Type
Biological
Intervention Name(s)
ChAdOx1 RVF
Intervention Description
Single dose ChAdOx1 vectored vaccine
Intervention Type
Other
Intervention Name(s)
Saline
Intervention Description
0.5ml saline placebo
Primary Outcome Measure Information:
Title
Assess the safety profile of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: AE
Description
Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination, occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination, occurrence of unsolicited adverse events for 28 days following the vaccination, and occurrence of serious adverse events during the whole study duration
Time Frame
The study duration: 3 months from vaccination
Title
Assess the safety profile of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: change in baseline: AE
Description
Change from baseline for safety laboratory measures: clinical blood test adverse events (full blood count, liver function tests and renal function) graded on a scaled adapted from the FDA healthy volunteer vaccine scale
Time Frame
The study duration: 3 months from vaccination
Secondary Outcome Measure Information:
Title
Assess the immunogenicity of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: GnGc protein antibodies
Description
Measures of immunogenicity to the ChAdOx1 RVF vaccine: * ELISA to quantify antibodies to GnGc proteins
Time Frame
The study duration: 3 months from vaccination
Title
Assess the immunogenicity of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: RVFV neutralising antibodies
Description
Measures of immunogenicity to the ChAdOx1 RVF vaccine: * RVFV neutralising antibody titres
Time Frame
The study duration: 3 months from vaccination
Title
Assess the immunogenicity of the candidate vaccine ChAdOx1 RVF in healthy adult volunteers in Uganda: ELISpot & flow cytometry
Description
Measures of immunogenicity to the ChAdOx1 RVF vaccine: * Ex vivo ELISpot and flow cytometry responses to GnGc
Time Frame
The study duration: 3 months from vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: The volunteer must satisfy all the following criteria to be eligible for the study: Male and female healthy adults aged 18 to 50 years Able and willing to provide written informed consent Able and willing (in the Investigator's opinion) to comply with all study requirements For females only, willingness to practice continuous effective contraception during the study. Females of childbearing potential must have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test immediately prior to study vaccine administration Agreement to refrain from blood donation during the course of the study Healthy in the investigator's clinical judgement basing on the medical history and physical examination performed at screening Healthy on the basis of clinical laboratory tests (within the institutional normal laboratory reference ranges) performed at screening. Willing to provide verifiable identification to the study team Volunteer must have a means to be contacted or be willing to provide locator information to the study team Volunteer must pass the Test of Understanding (TOU) Exclusion Criteria: The volunteer may not enter the study if any of the following apply: Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period Prior receipt of an investigational vaccine as it may impact on interpretation of the trial data. 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) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) History of allergic disease or reactions likely to be exacerbated by any component of the vaccine Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema. Any history of anaphylaxis in relation to vaccination Pregnancy, lactation or willingness/intention to become pregnant during the study 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 Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture Acute illness or temperature ≥37.5°C/99.5°F on the day of vaccination. Volunteer may be rescheduled for enrolment at a later date. Major surgery (per the investigator's judgement) within 4 weeks prior to screening or planned major surgery through the course of the study Any other serious chronic illness requiring hospital specialist supervision Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 14 units every week Suspected or known injecting drug abuse in the 5 years preceding enrolment Seropositive for hepatitis B surface antigen (HBsAg) Seropositive for hepatitis C virus (antibodies to HCV) Any clinically significant abnormal finding on screening biochemistry, haematology and coagulation 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 Prior natural exposure to RVFV as determined by seropositivity for RVFV antigens by ELISA.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pontiano Kaleebu, PhD
Organizational Affiliation
MRC/UVRI and LSHTM Uganda Research Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
MRC/UVRI and LSHTM Uganda Research Unit
City
Entebbe
Country
Uganda

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study to Assess the New Candidate Rift Valley Fever Virus Vaccine in Healthy Adults

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