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

Sponsor

Vir Biotechnology, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04725877

Collaborator

Bill and Melinda Gates Foundation (Other)

Enrollment

Locations

Arms

48.1

Anticipated Duration (Months)

6.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HIV I Infection	Biological: VIR-1111 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Dec 28, 2020

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VIR-1111	Biological: VIR-1111 VIR-1111 is administered as a 1 mL subcutaneous injection in the deltoid area of the upper arm on Day 1 and Day 57.
Placebo Comparator: Placebo	Drug: Placebo A placebo (Tris NaCl Sucrose formulation buffer) given by subcutaneous injection.

Arm

Intervention/Treatment

Experimental: VIR-1111

Biological: VIR-1111

VIR-1111 is administered as a 1 mL subcutaneous injection in the deltoid area of the upper arm on Day 1 and Day 57.

Placebo Comparator: Placebo

Drug: Placebo

A placebo (Tris NaCl Sucrose formulation buffer) given by subcutaneous injection.

Outcome Measures

Primary Outcome Measures

Number of participants with any treatment-emergent adverse events (AEs) [Day 1 through 36 weeks]
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.
Number of participants with any serious AEs (SAEs) [Day 1 through 36 weeks]
An SAE is any life-threatening event or one that results in hospitalization, significant disability/incapacity, death or congenital anomaly/birth defect.
Number of participants with any local site reactogenicity event after first dose [Day 1 through 14 days 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.
Number of participants with any local site reactogenicity event after second dose [Day 1 through 14 days 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.
Number of participants with any systemic reactogenicity event after first dose [Day 1 through 14 days 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.
Number of participants with any systemic reactogenicity event after second dose [Day 1 through 14 days 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.
Number of participants with any treatment-emergent clinical laboratory abnormalities (chemistry, hematology and liver function tests) [Day 1 through 36 weeks]
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.
Number of participants with CMV vector viremia (blood) [Day 1 through 36 weeks]
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.
Number of participants with CMV vector shedding (urine and saliva) [Day 1 through 36 weeks]
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.

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site	Miami	Florida	United States	33122
2	Investigative Site	Boston	Massachusetts	United States	02115
3	Investigative Site	Seattle	Washington	United States	98104
4	Investigative Site	Madison	Wisconsin	United States	53704