VIR-1111: A Prototype Human CMV-based Vaccine for Human Immunodeficiency Virus (HIV) in Healthy Volunteers

Study Overview
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Brief Summary
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This is a Phase 1a, first in human study in which healthy adult participants who are considered to be at low-risk for HIV infection and are seropositive for cytomegalovirus (CMV) will receive two doses of VIR-1111 or placebo. These participants will be assessed for safety, reactogenicity, tolerability and immunogenicity. 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 1a, Randomized, Placebo-Controlled Study to Evaluate the Safety and Immunogenicity of a Prototype Human CMV-based Vaccine for Human Immunodeficiency Virus (HIV) in Healthy Volunteers

Conditions
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HIV I Infection

Intervention / Treatment
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* Biological: VIR-1111
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or healthy females of non-child-bearing potential between the ages of 18 to 50 at the time of screening Positive CMV serostatus 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 Willing to use condoms during intercourse through Week 36 or the end of the study Willing to undergo HIV testing, risk reduction counseling, and receive HIV test results Willing to comply with the protocol requirements regarding donation of blood, sperm or other tissues In the opinion of the Investigator, generally in good health as determined from medical history and no clinically significant findings from physical examinations, vital signs, and laboratory values Exclusion Criteria: Live in a home with children under the age of 6 Routine provision of child care to children under the age of 6 Have close contact with immunocompromised individuals Have close contact with pregnant women or a partner planning to become pregnant during the course of the study Health care provider who routinely comes into contact with immunosuppressed patients or pregnant women Participant is immunocompromised Participant has an autoimmune disorder Positive HIV test at the time of study screening Receipt of another investigational HIV or CMV vaccine candidate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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-1111<br> | Biological: VIR-1111<br>* VIR-1111 is administered as a 1 mL subcutaneous injection in the deltoid area of the upper arm on Day 1 and Day 57.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* A placebo (Tris NaCl Sucrose formulation buffer) given by subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with any treatment-emergent adverse events (AEs) | A treatment-emergent AE is any AE with an onset date on or after the investigational product start date and no later than 36 weeks after permanent discontinuation of the investigational product. | Day 1 through 36 weeks | 
| Number of participants with any serious AEs (SAEs) | An SAE is any life-threatening event or one that results in hospitalization, significant disability/incapacity, death or congenital anomaly/birth defect. | Day 1 through 36 weeks | 
| Number of participants with any local site reactogenicity event after first dose | Signs and symptoms will be captured at the injection site (e.g., pain/tenderness, swelling, redness and induration) through self-assessment via participant diaries and in-person clinical assessments. | Day 1 through 14 days after first dose | 
| Number of participants with any local site reactogenicity event after second dose | Signs and symptoms will be captured at the injection site (e.g., pain/tenderness, swelling, redness and induration) through self-assessment via participant diaries and in-person clinical assessments. | Day 1 through 14 days after second dose | 
| Number of participants with any systemic reactogenicity event after first dose | Systemic signs and symptoms (fever, headache, fatigue, arthralgia, myalgia, malaise, nausea, vomiting or chills) through self-assessment via participant diaries and in-person clinical assessments. | Day 1 through 14 days after first dose | 
| Number of participants with any systemic reactogenicity event after second dose | Systemic signs and symptoms (fever, headache, fatigue, arthralgia, myalgia, malaise, nausea, vomiting or chills) through self-assessment via participant diaries and in-person clinical assessments. | Day 1 through 14 days after second dose | 
| Number of participants with any treatment-emergent clinical laboratory abnormalities (chemistry, hematology and liver function tests) | A treatment-emergent clinical laboratory abnormality is a clinical laboratory value that increases at least 1 toxicity grade from baseline at any postbaseline timepoint up to 30 days after permanent discontinuation of study drug. Clinical laboratory abnormalities are graded using DAIDS Table for Grading and Severity of Adult and Pediatric Events, Corrected Version 2.1, July 2017. | Day 1 through 36 weeks | 
| Number of participants with CMV vector viremia (blood) | Quantitative polymerase chain reaction (qPCR) for CMV will be performed on participant blood samples collected throughout the study. Positive samples will undergo follow-up confirmatory PCR testing to differentiate wild-type CMV from CMV vaccine vector sequences. | Day 1 through 36 weeks | 
| Number of participants with CMV vector shedding (urine and saliva) | Quantitative polymerase chain reaction (qPCR) for CMV will be performed on both saliva and urine samples collected from participants throughout the study to monitor for viral shedding. Positive samples will undergo follow-up confirmatory PCR testing to differentiate wild-type CMV from CMV vaccine vector sequences. | Day 1 through 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of CMV-specific CD8 T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR TNFa |  | 0-36 weeks | 
| Frequency of CMV-specific CD4 T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR CD154 |  | 0-36 weeks | 
| Frequency of HIV-1 Clade A Gag-specific CD4 T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR TNFa AND/OR CD154 |  | 0-36 weeks | 
| Frequency of HIV-1 Clade A Gag-specific CD8 T cells T cells via peptide stimulation, intracellular cytokine staining and flow cytometry to detect IL-2 AND/OR IFNg AND/OR TNFa |  | 0-36 weeks | 
| Memory phenotype of CMV-specific CD4 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95. |  | 0-36 weeks | 
| Memory phenotype of CMV-specific CD8 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95 |  | 0-36 weeks | 
| Memory phenotype of HIV-1 Clade A Gag-specific CD4 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95 |  | 0-36 weeks | 
| Memory phenotype of HIV-1 Clade A Gag-specific CD8 T cells via flow cytometry analysis of CD45RA, CCR7, CD27, CD28 AND/OR CD95 |  | 0-36 weeks | 
| Binding titers of CMV-specific IgG antibodies |  | 0-36 weeks | 
| Binding titers of HIV Clade A Gag-specific IgG antibodies |  | 0-36 weeks | 

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