Safety and Immunogenicity of the Candidate Rabies Vaccine ChAdOx2 RabG

NCT04162600 | Terminated Phase 1 DMC

• 1 other identifier: RAB001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human, open-label, dose escalation, phase I clinical trial to assess the safety and immunogenicity of the candidate ChAdOx2 RabG vaccine in healthy UK volunteers aged 18-65. The vaccine will be administered intramuscularly (IM).

Conditions

Rabies

Keywords

Vaccine

Outcome Measures

Primary Outcomes (4)

• Safety and tolerability of ChAdOx2 RabG in healthy volunteers given as a standalone vaccine at different doses 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 and tolerability of ChAdOx2 RabG in healthy volunteers given as a standalone vaccine at different doses 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 and tolerability of ChAdOx2 RabG in healthy volunteers given as a standalone vaccine at different doses assessed by the occurrence of serious adverse events.

  Occurrence of serious adverse events

  SAEs will be collected from enrolment until the end of the follow-up period.(8 weeks)

• Safety and tolerability of ChAdOx2 RabG in healthy volunteers given as a standalone vaccine at different doses 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.

  At Day 0 (baseline), day 2, day 7, day 28 and day 56 post vaccination

Secondary Outcomes (1)

• Immunogenicity of the ChAdOx2 RabG vaccine

  Day 365

Other Outcomes (3)

• Immunological memory induced by ChAdOx2 RabG

  Between days 365 and 386

• Timecourse of EBV and CMV shedding

  Study Duration (386 days)

• Level of EBV and CMV shedding

  Study Duration (386 days)

Study Arms (3)

5 x 10^9 vp of ChAdOx2 RabG

EXPERIMENTAL

Volunteers will receive a standalone dose of ChAdOx2 RabG 5 x 10\^9 vp vaccination intramuscularly. Optional extended follow-up, volunteers will receive a complete pre-exposure prophylactic course of an existing rabies vaccine.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

2.5 x 10^10 vp of ChAdOx2 RabG

EXPERIMENTAL

Volunteers will receive a standalone dose of ChAdOx2 RabG 2.5 x 10\^10 vp vaccination intramuscularly. Optional extended follow-up, volunteers will receive a complete pre-exposure prophylactic course of an existing rabies vaccine.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

5 x 10^10 vp of ChAdOx2 RabG

EXPERIMENTAL

Volunteers will receive a standalone dose of ChAdOx2 RabG 5 x 10\^10 vp vaccination intramuscularly. Optional extended follow-up, volunteers will receive a complete pre-exposure prophylactic course of an existing rabies vaccine.

Biological: ChAdOx2 RabG; Biological: Inactivated Rabies Vaccine

Interventions

ChAdOx2 RabG BIOLOGICAL

Single dose of ChAdOx2 RabG at different concentrations: 5 x 10\^9 vp, 2.5 x 10\^10 vp, 5 x 10\^10 vp

2.5 x 10^10 vp of ChAdOx2 RabG

Inactivated Rabies Vaccine BIOLOGICAL

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

2.5 x 10^10 vp of ChAdOx2 RabG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults aged 18 to 65 years.
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Willing to allow the investigators to discuss the volunteer's medical history with their GP.
• For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of screening and vaccination(s).
• Agreement to refrain from blood donation during the course of the study.
• Provide written informed consent.

You may not qualify if:

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period. To be re- confirmed at the enrolment visit.
• Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored 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) 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 (eg. Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
• \. Individuals who have previously experienced episodes of capillary leak syndrome.
• \. History of confirmed major thrombotic event (including cerebral venous sinus thrombosis, deep vein thrombosis, pulmonary embolism).
• \. History of antiphospholipid syndrome. 16. History of prior receipt of unfractionated heparin. 17. History of heparin induced thrombocytopenia. 18. 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. 20. Suspected or known injecting drug abuse in the 5 years preceding enrolment. 21. Detectable circulating hepatitis B surface antigen (HBsAg). 22. Seropositive for hepatitis C virus (antibodies to HCV). 23. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis. 24. 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.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

CCVTM, University of Oxford, Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Jenkin D, Ritchie AJ, Aboagye J, Fedosyuk S, Thorley L, Provstgaad-Morys S, Sanders H, Bellamy D, Makinson R, Xiang ZQ, Bolam E, Tarrant R, Ramos Lopez F, Platt A, Poulton I, Green C, Ertl HCJ, Ewer KJ, Douglas AD. Safety and immunogenicity of a simian-adenovirus-vectored rabies vaccine: an open-label, non-randomised, dose-escalation, first-in-human, single-centre, phase 1 clinical trial. Lancet Microbe. 2022 Sep;3(9):e663-e671. doi: 10.1016/S2666-5247(22)00126-4. Epub 2022 Jul 27.

  PMID: 35907430 DERIVED

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2019
• First Posted: November 14, 2019
• Study Start: January 2, 2020
• Primary Completion: July 10, 2024
• Study Completion: July 10, 2024
• Last Updated: November 8, 2024

Record last verified: 2024-07

Locations

GB (1)