A Phase Ib/II Study of the Safety and Immunogenicity of the Candidate Rabies Vaccine ChAdOx2 RabG

NCT04270838 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: RAB002
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase Ib/II, open-label, head-to-head, age de-escalation dose-escalation, partially randomized trial to study the safety and immunogenicity of the candidate rabies vaccine ChAdOx2 RabG in healthy adults (age 18-45 years) and young children (age 2-6 years). ChAdOx2 RabG will be administered intramuscularly and licensed rabies vaccine will be given by intradermal injection.

Conditions

Rabies

Keywords

Vaccine

Outcome Measures

Primary Outcomes (4)

• Safety profile of ChAdOx2 RabG in healthy adult volunteers (18-45 years) and young children (2-6 years) residing in a rabies-endemic country assessed by the occurrence of solicited adverse events.

  Occurrence of solicited local and systemic adverse events (i.e: pain, redness, swelling and pruritus at injection site and temperature, feverishness, myalgia, arthralgia, malaise, headache, fatigue and nausea).

  Assessment of solicited AEs in the first 7 days post vaccination

• Safety profile of ChAdOx2 RabG in healthy adult volunteers (18-45 years) and young children (2-6 years) residing in a rabies-endemic country assessed by the occurrence of solicited adverse events.

  Occurrence of unsolicited local and systemic adverse events

  Unsolicited AEs to be assessed up to 28 days post vaccination

• Safety profile of ChAdOx2 RabG in healthy adult volunteers (18-45 years) and young children (2-6 years) residing in a rabies-endemic country assessed by the occurrence of solicited adverse events.

  Occurrence of serious adverse events

  SAEs will be collected from enrolment until the end of the follow-up period (Day 1839)

• Safety profile of ChAdOx2 RabG in healthy adult volunteers (18-45 years) and young children (2-6 years) residing in a rabies-endemic country assessed by the occurrence of solicited adverse events.

  Occurrence of laboratory adverse events defined as clinically significant changes from baseline. Haematology (Full Blood Count) and Biochemistry (Kidney and Liver Function Tests) will be assessed.

  Clinical Laboratory AEs to be assessed up to 28 days post vaccination

Secondary Outcomes (2)

• Immunogenicity of ChAdOx2 RabG administered to adults and young children residing in a rabies endemic country following primary vaccination, including the length of response maintenance, and secondary (recall) response.

  At Days 0, 28, 56, 186, 365, 730, 1095, 1460, 1825

• Comparison of immunogenicity of ChAdOx2 RabG with a single visit two site intradermal IRV PrEP regimen

  At days SPEP+0 and SPEP+7

Study Arms (10)

Group AC1 (Adult low dose)

EXPERIMENTAL

Volunteers aged 18-45 years. Volunteers will receive a standalone dose of 2.5×10\^10 vp ChAdOx2 RabG on D0. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

Group AC2 (Adult high dose)

EXPERIMENTAL

Volunteers aged 18-45 years. Volunteers will receive a standalone dose of 5×10\^10 vp ChAdOx2 RabG. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

Group AC3 (Adult preferred dose)

EXPERIMENTAL

Volunteers aged 18-45 years. Volunteers will receive a preferred dose of ChAdOx2 RabG on D0. The adult preferred dose will be 2.5×10\^10 vp OR 5×10\^10 vp. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

Group AV1 (Adult single-visit Verobab)

EXPERIMENTAL

Volunteers aged 18-45 years. Volunteers will receive Rabies IRV on D0. Volunteers will receive two further doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: Inactivated Rabies Vaccine

PC1a (Paediatric low dose)

EXPERIMENTAL

Volunteers aged 2-6 years. Volunteers will receive a standalone dose of 1×10\^10 vp ChAdOx2 RabG on D0. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

PC1b (Paediatric low dose)

EXPERIMENTAL

Volunteers aged 2-6 years. Volunteers will receive a half adult preferred dose of ChAdOx2 RabG on D0. The adult preferred dose will be 2.5×10\^10 vp OR 5×10\^10 vp. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

PC2 (Paediatric high dose)

EXPERIMENTAL

Volunteers aged 2-6 years. Volunteers will receive a full adult preferred dose of ChAdOx2 RabG on D0. The adult preferred dose will be 2.5×10\^10 vp OR 5×10\^10 vp. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

PC3 (Paediatric preferred dose)

EXPERIMENTAL

Volunteers aged 2-6 years. Volunteers will receive a paediatric preferred dose of ChAdOx2 RabG on D0. The paediatric preferred dose will be 50-100% of the adult preferred dose. Volunteers will receive two doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

PV1 (Paediatric single-visit Verobab)

EXPERIMENTAL

Volunteers aged 2-6 years. Volunteers will receive Rabies IRV (Verorab) as a 2 site ID on D0. Volunteers will receive two further doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: Inactivated Rabies Vaccine

PV2 (Paediatric two-visit Verobab)

EXPERIMENTAL

Volunteers aged 2-6 years. Volunteers will receive Rabies IRV (Verorab) as a 2 site ID on D0. Volunteers will receive two further doses of Rabies IRV as simulated post-exposure prophylaxis (SPEP), 14 days apart during the follow-up period. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. Participants who return a virus neutralising antibody (VNA) result below 0.5IU/mL will be randomised (1:1 ratio) for the SPEP+0 visit to happen at the next available visit or at the final annual visit. Any participants who do not return a VNA result below 0.5IU/mL will have their SPEP+0 visit take place at the final annual visit.

Biological: Inactivated Rabies Vaccine

Interventions

ChAdOx2 RabG BIOLOGICAL

Single dose of ChAdOx2 RabG at different concentrations: 1x10\^10 and 5x10\^10

Group AC1 (Adult low dose); Group AC2 (Adult high dose); Group AC3 (Adult preferred dose); PC1a (Paediatric low dose); PC1b (Paediatric low dose); PC2 (Paediatric high dose); PC3 (Paediatric preferred dose)

Inactivated Rabies Vaccine BIOLOGICAL

A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units

Also known as: Verorab

Group AC1 (Adult low dose); Group AC2 (Adult high dose); Group AC3 (Adult preferred dose); Group AV1 (Adult single-visit Verobab); PC1a (Paediatric low dose); PC1b (Paediatric low dose); PC2 (Paediatric high dose); PC3 (Paediatric preferred dose); PV1 (Paediatric single-visit Verobab); PV2 (Paediatric two-visit Verobab)

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adult groups: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent.
• Adult groups (Female only participants): Must be non-pregnant (as demonstrated by a negative urine pregnancy test) and willing to use an effective form of contraception. Or if they agree to an extended period of follow-up of up to 5.5 years, use an effective form of contraception during the first year of enrolment in the study).
• Paediatric groups: Healthy male or female young children aged 2-6 years at the time of enrolment with signed consent obtained from parents or guardians.
• Paediatric groups: completion of the Expanded Programme on Immunisation (EPI) at least 6 months prior to study enrolment.
• Planned long-term (at least 61 months from the date of the first vaccination) or permanent residence in Bagamoyo town.
• Adults with a Body Mass Index (BMI) 18 to 35 Kg/m2; or young children with Z-score of weight-for-age within ±2SD.
• Correctly answer all 10 questions on the protocol and study procedures understanding questionnaire within 2 attempts.

You may not qualify if:

• Clinically significant congenital abnormalities as judged by the PI or other delegated individual.
• Clinically significant history of skin disorder, allergy, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease and neurological illness 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 as judged by the PI or other delegated individual.
• 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).
• Any condition which would place the individual at elevated risk of serious COVID-19 infection, or any other factor which may make the individual eligible for priority COVID-19 vaccination (i.e. ahead of others in their age group).
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, including IRVs e.g. amphotericin B, chlortetracycline, neomycin, polymyxin, streptomycin
• Any history of anaphylaxis in relation to vaccination.
• Clinically significant laboratory abnormality as judged by the PI or other delegated individual.
• Receipt of any previous rabies vaccinations, including an incomplete course.
• History of vaccination with previous adenoviral vectored vaccines in the 6 months prior to enrolment in the study, or of vaccination with any other vaccine (including non-adenovirus-vectored COVID-19 vaccines) in the 28 days prior to enrolment.
• Planned / likely receipt of any other vaccine within 28 days after enrolment.
• 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, or continuous anticoagulation e.g., with warfarin
• History of confirmed major thrombotic event, (including cerebral venous sinus thrombosis, deep vein thrombosis, pulmonary embolism) or,
• History of antiphospholipid syndrome.
• History of prior receipt of unfractionated heparin

Sponsors & Collaborators

• University of Oxford: lead
• Ifakara Health Institute: collaborator

Study Sites (1)

IHI Clinical Trial Facility

Bagamoyo, Tanzania

Location

MeSH Terms

Conditions

Rabies

Condition Hierarchy (Ancestors)

Rhabdoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections

Study Officials

• Alexander D Douglas

  Jenner Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: February 17, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

TA (1)