A Phase Ib Study of the Safety and Immunogenicity of the Candidate Rabies Vaccine ChAdOx2 RabG
Study Details
Study Description
Brief Summary
This is a Phase Ib, 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
A total of 120 participants will be recruited into 10 groups in Bagamoyo, Tanzania. The duration of the entire study will be 13 months per participant from the time of first vaccination. ChAdOx2 RabG will be administered intramuscularly and licensed rabies vaccine (Verorab) will be given by intradermal injection at two to four anatomical sites (deltoids, thighs or suprascapular areas).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group AC1 (Adult low dose) Volunteers aged 18-45 years. Volunteers will receive a standalone dose of 2.5×10^10 vp ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (stimulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: Group AC2 (Adult high dose) Volunteers aged 18-45 years. Volunteers will receive a standalone dose of 5×10^10 vp ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: Group AC3 (Adult preferred dose) Volunteers aged 18-45 years. Volunteers will receive a preferred dose of ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). The adult preferred dose will be 2.5×10^10 vp OR 5×10^10 vp. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: Group AV1 (Adult single-visit Verobab) Volunteers aged 18-45 years. Volunteers will receive Rabies IRV on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: PC1a (Paediatric low dose) Volunteers aged 2-6 years. Volunteers will receive a standalone dose of 1×10^10 vp ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: PC1b (Paediatric low dose) Volunteers aged 2-6 years. Volunteers will receive a half adult preferred dose of ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). The adult preferred dose will be 2.5×10^10 vp OR 5×10^10 vp. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: PC2 (Paediatric high dose) Volunteers aged 2-6 years. Volunteers will receive a full adult preferred dose of ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). The adult preferred dose will be 2.5×10^10 vp OR 5×10^10 vp. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: PC3 (Paediatric preferred dose) Volunteers aged 2-6 years. Volunteers will receive a paediatric preferred dose of ChAdOx2 RabG on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). The paediatric preferred dose will be 50-100% of the adult preferred dose. All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: ChAdOx2 RabG
Single dose of ChAdOx2 RabG at different concentrations: 1x10^10 and 5x10^10
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: PV1 (Paediatric single-visit Verobab) Volunteers aged 2-6 years. Volunteers will receive Rabies IRV (Verorab) as a 2 site ID on D0 followed by two doses of Rabies IRV (simulated PEP), one on D365 (SPEP+0) and one on D379 (SPEP+14). All participants will receive Verorab as a 4 site ID on SPEP+0, and Verorab as a 2 site ID on SPEP+14. |
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
| Experimental: PV2 (Paediatric two-visit Verobab) Volunteers aged 2-6 years. Volunteers will receive Rabies IRV (Verorab) as a 2 site ID on D0 followed by another dose on D7. All participants will also receive Verorab as a 4 site ID on D365 (SPEP+0) and Verorab as a 2 site ID on D379 (SPEP+14). |
Biological: Inactivated Rabies Vaccine
A complete pre-exposure prophylactic course of an existing rabies vaccine, ≥2.5 international units
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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. [Assessment of solicited AEs in the first 7 days post vaccination]
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).
- 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. [Unsolicited AEs to be assessed up to 28 days post vaccination]
Occurrence of unsolicited local and systemic adverse events
- 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. [SAEs will be collected from enrolment until the end of the follow-up period (Day 372)]
Occurrence of serious adverse events
- 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. [Clinical Laboratory AEs to be assessed up to 28 days post vaccination]
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.
Secondary Outcome Measures
- Immunogenicity of ChAdOx2 RabG administered to adults and young children residing in a rabies endemic country following primary vaccination and secondary (recall) response. [At Days 0, 28, 365]
Rapid fluorescent focus inhibition test (RFFIT) of rabies virus neutralising antibody
- Comparison of immunogenicity of ChAdOx2 RabG with a single visit two site intradermal IRV PrEP regimen [At days 365 and 372]
Anamnestic rabies virus neutralising antibody response as assessed by rapid fluorescent focus inhibition test (RFFIT), at 7 days following simulated rabies virus exposure through IRV administration
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Group 1: Healthy male or female adults aged 18-45 years at the time of enrolment with signed consent.
-
Group 1 (Female only participants): Must be non-pregnant (as demonstrated by a negative urine pregnancy test) and willing to use an effective form of contraception.
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Groups 2a, 2b and 2c: Healthy male or female young children aged 2-6 years at the time of enrolment with signed consent obtained from parents or guardians.
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Groups 2a, 2b and 2c: completion of the Expanded Programme on Immunisation (EPI) at least 6 months prior to study enrolment.
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Planned long-term (at least 12 months from the date of the first vaccination) or permanent residence in Bagamoyo town.
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Adults with a Body Mass Index (BMI) 18 to 35 Kg/m2; or young children with Z-score of weight-for-age within ±2SD.
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Correctly answer all 10 questions on the protocol and study procedures understanding questionnaire within 2 attempts.
Exclusion Criteria:
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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.
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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).
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History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
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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
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Any history of anaphylaxis in relation to vaccination.
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Clinically significant laboratory abnormality as judged by the PI or other delegated individual.
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Receipt of any previous rabies vaccinations, including an incomplete course.
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History of vaccination with previous experimental adenoviral vectored vaccines.
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Receipt of any blood products/ immunoglobulins within the three months preceding the planned administration of the vaccine candidate.
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Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period.
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Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C (HCV IgG).
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Likelihood of travel away from the study area.
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Female participant who is pregnant, lactating or planning pregnancy during the course of the trial.
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Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
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Any other significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | IHI Clinical Trial Facility | Bagamoyo | Tanzania |
Sponsors and Collaborators
- University of Oxford
- Ifakara Health Institute
Investigators
- Principal Investigator: Alexander D Douglas, Jenner Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RAB002