A Study to Assess Safety and Immunogenicity of Conserved Mosaic HIV-1 Vaccines

Phase 1

Completed

Conditions: HIV

Interventions: Biological: ChAdOx1.tHIVconsv1 (C1)
Biological: MVA.tHIVconsv3 (M3)
Biological: MVA.tHIVconsv4 (M4)

Registration Number: NCT04586673

Lead Sponsor: University of Oxford

Brief Summary: The object of the study is to assess the safety profile of candidate vaccines ChAdOx1.tHIVconsv1, MVA.tHIVconsv3 and MVA.tHIVcnsv4 administered sequentially in healthy HIV-1/2 negative adult volunteers.

In addition, the study will assess the immune responses generated of the candidate vaccines ChAdOx1.tHIVconsv1, MV.tHIVconsv3 and MVA.tHIVconsv4 administered sequentially in healthy HIV-1/2 negative adult volunteers.

3 healthy, HIV-1 negative adult volunteers will receive one vaccination of low dose ChAdOx1.tHIVconsv1. A further 10 healthy, HIV-1 negative adult volunteers will receive a higher dose of ChAdOx1.tHIVconsv1, followed by one vaccination each of MVA.tHIVconsv3 and MVA.tHIVconsv4 4 weeks later.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Healthy adult aged 18-65 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
Women of child-bearing potential agree to practice continuous effective contraception during the study and test negative for pregnancy on the day(s) of screening and vaccination
For sexually active men, willingness to use barrier methods for the purposes of contraception from screening until 4 months after the last vaccination
Agreement to refrain from blood donation during the course of the study
In the opinion of the Investigators, the volunteer has understood the information provided Written informed consent must be given before any study-related procedures are performed
Willing to undergo HCV, HBV, syphilis and HIV testing and counselling and receive test results

Exclusion Criteria

Confirmed HIV-1 or HIV-2 infection
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 a recombinant simian adenoviral vaccine prior to enrolment
Planned receipt of another adenoviral vectored vaccine within 90 days after the vaccination with the ChAdOx1.tHIVconsv1 IMP
Receipt of any investigational HIV-1/2 vaccine
Receipt of live attenuated vaccine within the previous 60 days or planned receipt within 60 days after vaccination with the IMP
Receipt of other vaccine, including influenza vaccine, within the previous 14 days or planned receipt within 14 days after vaccination with the IMP
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-1/2 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)
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
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
Suspected or known injecting drug abuse in the 5 years preceding enrolment
Reported high-risk behaviour for HIV-1/2 infection. High-risk behaviour for HIV-1/2 infection is defined as follows. Within the previous 12 months the volunteer has:
- Had unprotected vaginal or anal sex with a person infected with HIV and not taking effective treatment, injecting drug users or casual partners (i.e., no continuing, established relationship)
- Engaged in sex work for money or drugs
- Used injection drugs
- Acquired one of the following sexually transmitted infection: chlamydia, gonorrhea and syphilis.
Seropositive for hepatitis B surface antigen (HBsAg)
Seropositive for hepatitis C virus (antibodies to HCV)
Untreated Syphilis: Treponemal IgG/IgM and positive RPR/TPPA AND no documentation of adequate treatment
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
ChADOx1.tHIVconsv1 higher dose	MVA.tHIVconsv3 (M3)	10 participants will receive one dose of ChAdOx1.tHIVconsv1 at 5 x 10\^10 vp and one dose each of MVA.tHIVconsv3 at 1 x 10\^8 pfu and MVA.tHIVconsv4 at 0.9 x 10\^8 pfu.
ChADOx1.tHIVconsv1 higher dose	ChAdOx1.tHIVconsv1 (C1)	10 participants will receive one dose of ChAdOx1.tHIVconsv1 at 5 x 10\^10 vp and one dose each of MVA.tHIVconsv3 at 1 x 10\^8 pfu and MVA.tHIVconsv4 at 0.9 x 10\^8 pfu.
ChAdOx1.tHIVconsv1 low dose	ChAdOx1.tHIVconsv1 (C1)	3 participants will receive one dose of ChAdOx1.tHIVconsv1 at 5 x 10\^9 vp
ChADOx1.tHIVconsv1 higher dose	MVA.tHIVconsv4 (M4)	10 participants will receive one dose of ChAdOx1.tHIVconsv1 at 5 x 10\^10 vp and one dose each of MVA.tHIVconsv3 at 1 x 10\^8 pfu and MVA.tHIVconsv4 at 0.9 x 10\^8 pfu.

Primary Outcome Measures

Name	Time	Method
Assessement of Safety	140 days	• Proportion of volunteers with vaccine related serious adverse events (SAEs) collected up to day 140 after enrollment.
Assement of Safety	up to 28 days after each vaccination	Proportion of volunteers with Grade 3 or 4 unsolicited adverse events (AEs) through 28 days post final vaccination
Assessment of Safety	up to day 7	Proportion of volunteers with local and systemic reactogenicity events from Day 0 to Day 6 post vaccination

Secondary Outcome Measures

Name	Time	Method
Assessment of the Immunogenicity of the ChAdOx1.tHIVconsv1 and MVA.tHIVconsv3 & 4 Vaccines Administered Sequentially.	Up to 5 months	The proportion of participants that develop T-cell responses to tHIVconsvx measured by IFN-gamma ELISpot assay