To Investigate Safety, Reactogenicity and Immunogenicity of VIR-1388 Compared With Placebo in Participants Without HIV

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of VIR 1388 in adults in good health without HIV.

Detailed Description
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This is a Phase 1, randomized, double-blind, placebo-controlled, multicenter study in adults aged 18 to 55 years in overall good health and without HIV. Participants will be enrolled concurrently into 1 of 3 dose levels of VIR-1388 or placebo. The overall study design includes 2 study parts, Part A and Part B. Part A will be a lead-in phase enrolling a limited number of HCMV seropositive persons of non-childbearing potential (PONCBP) with a frequent safety monitoring schedule. Part B will expand enrollment into a broader population of HCMV-seropositive participants, including persons of childbearing potential required to use 2 forms of contraception and maintains a similar overall safety monitoring schedule as Part A . There is an optional long-term follow-up study that would lengthen study participation for up to 3 years post-first dose.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Clinical Study to Evaluate the Safety, Reactogenicity and Immunogenicity of the HCMV-HIV Vaccine Candidate VIR-1388 in Adult Participants With Overall Good Health and Without HIV

Conditions
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HIV I Infection

Intervention / Treatment
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* Biological: VIR-1388
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In overall good health as determined by medical history, physical exam, and laboratory values HIV uninfected CMV seropositive Willing to use condoms during intercourse for the duration of the study Assessed by clinic staff as being low risk for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last protocol visit Childbearing status Part A: Only participants of non-childbearing potential Part B: Participants of childbearing potential must be on 2 forms of contraception and not planning on becoming pregnant for the duration of the study Exclusion Criteria: Participant is immunocompromised Participant has an autoimmune disorder Immunocompromised individuals Participants having intimate contact with immunocompromised individuals Participants having intimate contact with a pregnant partner or partner planning to become pregnant Participants who are breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VIR-1388, 5×10^4 ffu<br>Study intervention will be administered at Day 1 and Day 85 via subcutaneous (SC) injections. | Biological: VIR-1388<br>* VIR-1388 is given by subcutaneous injection<br>|
| Experimental: VIR-1388, 5×10^5 ffu<br>Study intervention will be administered at Day 1 and Day 85 via subcutaneous (SC) injections. | Biological: VIR-1388<br>* VIR-1388 is given by subcutaneous injection<br>|
| Experimental: VIR-1388, 5×10^6 ffu<br>Study intervention will be administered at Day 1 and Day 85 via subcutaneous (SC) injections. | Biological: VIR-1388<br>* VIR-1388 is given by subcutaneous injection<br>|
| Placebo Comparator: Placebo<br>Study intervention will be administered at Day 1 and Day 85 via subcutaneous (SC) injections. | Biological: Placebo<br>* The HT Diluent Placebo is HT buffer (20 mM histidine, 10% trehalose-dihydrate, pH 7.2) and contains no active ingredient and will be administered by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of unsolicited, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), new-onset chronic diseases (NOCDs) and medically attended adverse events (MAAEs) | Events will be graded as per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 | 12 months | 
| Incidence of solicited local site and systemic reactogenicity events | Events will be graded as per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 | 14 days after administration of each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of HIV-1 Mfuse1-specific CD4 T cells | As measured by intracellular cytokine staining (ICS) and flow cytometry | 12 months | 
| Frequency of HIV-1 Mfuse1-specific CD8 T cells | As measured by intracellular cytokine staining (ICS) and flow cytometry | 12 months | 
| Memory phenotype of HIV-1 Mfuse1-specific CD4 T cells | As determined by flow cytometry analysis | 12 months | 
| Memory phenotype of HIV-1 Mfuse1-specific CD8 T cells | As determined by flow cytometry analysis | 12 months | 
| Number of participants with VIR-1388 vector viremia in plasma | Detected by quantitative polymerase chain reaction(qPCR) of plasma | 12 months | 
| Number of participants with VIR-1388 vector shedding in saliva and urine | Detected by quantitative polymerase chain reaction(qPCR) of saliva and urine | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Vaccine, CMV, Cytomegalovirus