Safety and Immunogenicity of a Candidate Rift Valley Fever Vaccine (RVF003)

NCT06799234 | Active Not Recruiting Phase 2 DMC

• 4 other identifiers: OxTREC 3/24KEMRI/SERU/CGMRC/314/4960PACTR202406789723926PPB/ECCT/24/07/03
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if ChAdOx1 RVF, a candidate vaccine against RVF, provides an adequate immune response and determine its safety among Kenyan adults. The main aims are:

• To assess the proportion of individuals mounting an immune response following vaccination with a single dose of ChAdOx1 RVF
• To monitor occurrence of any adverse events following vaccination
• To assess whether two doses of ChAdOx1 RVF elicit an immune response that is more durable than that generated by a single dose of ChAdOx1 RVF Researchers will compare ChAdOx1 RVF vaccine to a rabies vaccine in 240 participants. Participants will be randomly allocated to one of three study groups and vaccinated with ChAdOx1 RVF or a control Rabies vaccine as follows. Group 1, composed of 120 participants, will receive a single dose of ChAdOx1 RVF vaccine at baseline and a single dose of rabies vaccine 3 months later. Group 2, composed of 60 adults, will receive two doses of ChAdOx1 RVF; the first dose at baseline and the second dose 3 months later. Group 3, composed of 60 adults, will receive two doses of rabies vaccine; the first dose at baseline and the second dose 3 months later. Participants will receive daily phone calls after each vaccination for the following six days to gather information on any symptoms they may experience. Participants will be instructed to contact the study team at any time should they experience any clinical symptoms. Blood samples will be collected at baseline (before vaccination) and at scheduled follow-up visits (8 visits over the duration of the study, i.e. days 7, 14, 28, 84, 91, 112, 365 and 540 after the first vaccination) for monitoring of immune responses. Up to 20mls of blood will be collected at each scheduled visit. Participants will be followed-up for 18 months from the first dose of vaccine. Adverse events following vaccination will be monitored throughout the study and reviewed by an independent Data and Safety Monitoring Board (DSMB)

Conditions

Rift Valley Fever

Outcome Measures

Primary Outcomes (1)

• To assess the rate of seroconversion for RVFV neutralizing antibodies 28 days post-vaccination with a single dose of ChAdOx1 RVF

  The proportion of vaccinees in each study group mounting neutralizing antibodies against live RVFV (i.e., seroconversion, as measured by FRNT80

  28 days post-vaccination with one dose of ChAdOx1 RVF

Secondary Outcomes (9)

• Geometric Mean Antibody Titre for neutralizing antibody titres (GMT) measured by FRNT80

  Days 0, 7, 14, 28, 84, 112, 365 and at 18 months

• Geometric mean antibody titre as measured by FRNT80 for IgG antibody titres

  Days 0, 7, 14, 28, 84, 112, 365 and at 18 months

• Spot Forming Units per 1,000,000 PBMCs (SFU/10⁶ PBMCs) for IFN-γ responses to RVFV Gn and Gc glycoproteins measured by enzyme-linked immunospot (ELISpot) assay

  Days 0, 7, 14, 28, 84, 112, 365 and at 18 months

• T-cells/10^6 PBMCs for multi-functional T cell responses to RVFV Gn and Gc glycoproteins as measured by flow cytometry.

  Days 0, 7, 14, 28, 84, 112, 365 and at 18 months.

• Number of Participants With Serious Adverse Events

  Throughout the study, upto 24 months.

Other Outcomes (3)

• To assess if anti-ChAdOx1 vector immunity influences response to ChAdOx1 RVF vaccination

  Day 0 and 84

• To estimate exposure to natural RVFV infection in the trial population

  Days 0, 28, 84, 112, 365 and at 18 months

• To assess whether sera from ChAdOx1 RVF vaccinees can passively protect animals from RVFV challenge

  Sera collected at day 28 post-vaccination

Study Arms (3)

Single dose ChAdOx1 RVF

EXPERIMENTAL

Group 1, composed of 120 participants, will receive a single dose of ChAdOx1 RVF vaccine at baseline and a single dose of rabies vaccine 3 months later

Biological: ChAdOx1 RVF; Biological: Rabies Vaccine

Double dose ChAdOx1 RVF

EXPERIMENTAL

Group 2, composed of 60 adults, will receive two doses of ChAdOx1 RVF; the first dose at baseline and the second dose 3 months later.

Biological: ChAdOx1 RVF

Rabies vaccine

ACTIVE COMPARATOR

Group 3, composed of 60 adults, will receive two doses of rabies vaccine; the first dose at baseline and the second dose 3 months later

Biological: Rabies Vaccine

Interventions

ChAdOx1 RVF BIOLOGICAL

One 0.36mL dose contains 5x10\^10vp ChAdOx1 RVF.

Double dose ChAdOx1 RVF; Single dose ChAdOx1 RVF

Rabies Vaccine BIOLOGICAL

1mL per dose

Rabies vaccine; Single dose ChAdOx1 RVF

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18-50 years
• For females only, willingness to practice continuous effective contraception up to one month following the second vaccination (i.e. duration of 4 months starting from enrolment) and a negative pregnancy test on the day(s) of screening. Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year when used consistently and correctly, in accordance with the product label. Examples of these include combined oral contraceptives, injectable progestogen, implants of etenogestrel or levonorgestrel, intrauterine device. Female participants will be asked for written confirmation of any family planning methods used by provision of health records. These records will be reviewed and counselling for adherence done at each study visit as per the protocol schedule of attendances. Participants who do not have adequate methods of contraception will be referred to their local dispensary where this will be dispensed for free or to Kilifi County Hospital (KCH). Costs incurred for obtaining contraception at KCH will be covered by the study.
• Agreement to refrain from blood donation during the course of the study
• Able and willing to provide written informed consent
• Plan to remain resident in the study area for 18 months following vaccination

You may not qualify if:

• Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrolment and/or planned receipt of a vaccine ≤30 days after enrolment
• 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 venipuncture
• 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 (e.g., more than 2 bottles of 500mls Tusker (beer) a day, more than 2 large glasses of 12% wine per day)
• Suspected or known injecting drug abuse in the 5 years preceding enrolment
• Seropositive for hepatitis B surface antigen (HBsAg)
• Seropositive for hepatitis C virus (HCV)

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

KEMRI-Wellcome Trust Research Programme

Kilifi, Coast, 254, Kenya

Location

MeSH Terms

Conditions

Rift Valley Fever

Interventions

Rabies Vaccines

Condition Hierarchy (Ancestors)

Hepatitis, Viral, Animal; Hepatitis, Animal; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Virus Diseases; Bunyaviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Hepatitis; Liver Diseases; Digestive System Diseases; Animal Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigators and participants will be blinded to the allocations. Only the pharmacist and the nurse administering the vaccine will be unblinded. The allocation will be to one of the three treatment arms per a computer-generated randomization schedule.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, controlled, double-blinded phase 2 trial

Study Record Dates

• First Submitted: September 20, 2024
• First Posted: January 29, 2025
• Study Start: July 8, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: November 17, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1)