Cytomegalovirus (CMV), HIV (Human Immunodeficiency Virus)
Conditions
Keywords
Vaccine, HIV Vaccine, Healthy Participants
Brief summary
This study is to test an experimental HIV Vaccine. About 12 participants, aged 18-55 years and who already have cytomegalovirus (CMV) will take part in this study. Participants will come to the clinic for scheduled visits about 21 times over 12 months.
Interventions
BIOLOGICALVIR-1388
Treatment 1 (T1): VIR-1388, 6.9 × 10\^7 ffu to be administered as three 1 mL subcutaneous (SC) injections (total dose = 3 mL) at week 0 (month 0) and week 12 (month 3).
BIOLOGICALPlacebo
Control 1 (C1): Placebo for VIR-1388 \[HT Diluent Placebo\] to be administered as three 1 mL SC injections (total dose = 3 mL) at week 0 (month 0) and week 12 (month 3).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. At least 18 years old at screening and up to 55 years old on day of enrollment. 2. Access to a participating clinical research site and willingness to be followed for the planned duration of the study. 3. Demonstrates an understanding of the study and is able and willing to provide informed consent. 4. Agrees not to enroll in another study of an investigational agent during participation in the trial. 5. In good general health according to the clinical judgment of the site investigator. 6. Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgment of the site investigator. 7. Willing to not donate blood, sperm, or other tissues until after the last required protocol clinic visit. 8. CMV seropositive 9. Systolic blood pressure of 90 to \< 140 mmHg and diastolic blood pressure of 50 to \< 90 mmHg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mmHg systolic and 90 mmHg diastolic. A single measurement ≥ 160 systolic mmHg or 100 mmHg diastolic during the current study evaluation is exclusionary. 10. Male volunteers with partners of pregnancy potential must agree to have their partners use contraception through the end of the study. 11. Women who are not of pregnancy potential or male volunteers. Any individual may be enrolled if they are not of pregnancy potential 12. Willingness to receive HIV test results. 13. Hemogram/complete blood count (CBC) Hemoglobin: * ≥ 11.0 g/dL for women * ≥ 13.0 g/dL for men 14. White blood cell (WBC) count = 2,500 to 12,000 cells/mm3 (WBC over 12,000/mm3 is not exclusionary if further evaluation shows general good health and if approval is granted). 15. Platelets = 125,000 to 550,000 cells/mm3. 16. Alanine aminotransferase (ALT) \< 1.25 × upper limit of institutional reference range 17. Aspartate aminotransferase (AST) (\< 1.25 × upper limit of normal (ULN)) based on institutional normal range 18. Alkaline phosphatase (ALP) ≤ 1.1 × ULN based on institutional normal range 19. Serum creatinine ≤ 1.1 × ULN based on institutional normal range 20. Total measured serum calcium level \>8.5 mg/dL. 21. Direct bilirubin levels \< 7.7 mic mol/L (0.45mg/dL) and total bilirubin \< 22.5 mic mol/L (1.3 mg/dL) (volunteers known to have Gilbert's Syndrome with an abnormal total bilirubin are not excluded) 22. Gamma-glutamyl transferase (GGT) \< 1.1 × ULN based on institutional normal range 23. Negative HIV-1 and -2 blood test 24. Negative hepatitis B surface antigen (HBsAg). 25. Negative anti-hepatitis C virus (HCV) antibodies or negative HCV nucleic acid test if the anti-HCV is positive. 26. All volunteers must use condoms for the duration of the study. ALL volunteers regardless of sex, reproductive status, or sex of partner(s) must use condoms as a barrier method to mitigate against potential VIR-1388 transmission to their partner(s) (in the event that shedding occurs).
Exclusion criteria
1. Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires approval. 2. Of pregnancy potential, pregnant, or breastfeeding. 3. Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life of more than 7 days (or unknown half-life) within the past year, approval is required for enrollment. 4. Use of (val)acyclovir, (val)ganciclovir, letermovir, foscarnet, or another antiviral with anti-CMV activity within 30 days prior to the first vaccination. Chronic or suppressive use of (val)acyclovir is not permitted. Short-term use (defined as less than 10 days) of (val)acyclovir is permitted at standard doses provided there have been no more than 2 courses of (val)acyclovir over the last 6 months. Topical use is not exclusionary. 5. Investigational HIV vaccine(s) or CMV-based vaccine received in prior vaccine trials. For volunteers who have received control/placebo in a TB vaccine trial, eligibility will be determined on a case-by-case basis. 6. Investigational vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be considered for vaccines that have subsequently undergone licensure by the FDA or by the national regulatory authority where the volunteer is enrolling. For volunteers who have received control/placebo in an experimental vaccine trial, eligibility will be determined on a case-by-case basis. For volunteers who have received an experimental vaccine(s) greater than 1 year ago, eligibility for enrollment will be determined on a case-by-case basis. 7. Receipt of any of the following within 4 weeks prior to enrollment: * Live replicating vaccine * Any mRNA-based vaccine with FDA licensure, FDA Emergency Use Authorization (EUA), or WHO Emergency Use Listing (EUL) * ACAM2000 vaccine \> 28 days prior with a vaccination scab still present 8. Receipt of any vaccines that are not covered in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Local Reactions | Day of vaccination through 14 days after each vaccination | Local reactogenicity signs and symptoms will be collected for a minimum of 14 days following receipt of any study product |
| Number of Participants with Systemic Reactions | Day of vaccination through 14 days after each vaccination | Systemic reactogenicity signs and symptoms will be collected for a minimum of 14 days following receipt of any study product |
| Number of Participants with Serious Adverse Events (SAEs) | Throughout the study, through 40 weeks after the last study product administration | — |
| Number of Participants with Medically Attended Adverse Events (MAAEs) | Throughout the study and for 40 weeks after the last study product administration | — |
| Number of Participants with Adverse Events of Special Interest (AESIs) | Throughout the study and for 40 weeks after the last study product administration | — |
| Number of Participants with Adverse Events Leading to Early Study Withdrawal | Throughout the study and for 40 weeks after the last study product administration | — |
| Number of Participants with Adverse Events Leading to Permanent Discontinuation of Study Product | Throughout the study and for 40 weeks after the last study product administration | — |
| Number of Participants with Adverse Events | Day of vaccination through 30 days after each vaccination | — |
| Magnitude of HIV-1 Mfuse1-Specific CD4 T-Cell Responses | Baseline and 4 and 8 weeks after each vaccination | Level of CD4 T-cell responses to HIV-1 Mfuse1, which contains parts of Gag, Pol, and Nef. Responses will be measured using intracellular cytokine staining (ICS) and flow cytometry. |
| Magnitude of HIV-1 Mfuse1-Specific CD8 T-Cell Responses | Baseline and 4 and 8 weeks after each vaccination | Level of CD8 T-cell responses to HIV-1 Mfuse1, which contains parts of Gag, Pol, and Nef. Responses will be measured using intracellular cytokine staining (ICS) and flow cytometry. |
| Function of HIV-1 Mfuse1-Specific CD4 T-Cell Responses | Baseline and 4 and 8 weeks after each vaccination | Function of CD4 T-cell responses to HIV-1 Mfuse1, as measured using intracellular cytokine staining (ICS) and flow cytometry |
| Function of HIV-1 Mfuse1-Specific CD8 T-Cell Responses | Baseline and 4 and 8 weeks after each vaccination | Function of CD8 T-cell responses to HIV-1 Mfuse1, as measured using intracellular cytokine staining (ICS) and flow cytometry |
| Phenotypic Profile of HIV-1 Mfuse1-Specific CD4 T-Cell Responses | Baseline and 4 and 8 weeks after each vaccination | Characteristics of CD4 T cells that respond to HIV-1 Mfuse1, as measured using flow cytometry |
| Phenotypic Profile of HIV-1 Mfuse1-Specific CD8 T-Cell Responses | Baseline and 4 and 8 weeks after each vaccination | Characteristics of CD8 T cells that respond to HIV-1 Mfuse1, as measured using flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With VIR-1388 Detected in Plasma | Vaccination Day 1 through Study Day 365 | Detection of VIR-1388 viremia by quantitative polymerase chain reaction (qPCR) in plasma |
| Number of Participants With VIR-1388 Detected in Saliva | Vaccination Day 1 through Study Day 365 | Detection of VIR-1388 shedding by qPCR in saliva |
| Number of Participants With VIR-1388 Detected in Urine | Vaccination Day 1 through Study Day 365 | Detection of VIR-1388 shedding by qPCR in urine |
| Magnitude of HIV-1 Mfuse1-Specific CD4 T-Cell Responses at Additional Timepoints responses to VIR-1388derived HIV-1 Mfuse1 (containing portions of Gag, Pol and Nef) | Additional timepoints during the study, including 2 weeks after each vaccination, and 12 weeks, 24 weeks, and 40 weeks after second vaccination | Level of CD4 T-cell responses to HIV-1 Mfuse1 at additional timepoints in participants who have a response in the primary assay. Responses will be measured using intracellular cytokine staining (ICS) and flow cytometry. |
| Magnitude of HIV-1 Mfuse1-Specific CD8 T-Cell Responses at Additional Timepoints | Additional timepoints during the study, including 2 weeks after each vaccination and 12 weeks, 24 weeks, and 40 weeks after second vaccination | Level of CD8 T-cell responses to HIV-1 Mfuse1 at additional timepoints in participants who have a response in the primary assay. Responses will be measured using intracellular cytokine staining (ICS) and flow cytometry. |
| Function of HIV-1 Mfuse1-Specific CD4 T-Cell Responses at Additional Timepoints | Additional timepoints during the study, including 2 weeks after each vaccination and 12 weeks, 24 weeks, and 40 weeks after second vaccination | Function of CD4 T-cell responses to HIV-1 Mfuse1 at additional timepoints in participants who have a response in the primary assay |
| Function of HIV-1 Mfuse1-Specific CD8 T-Cell Responses at Additional Timepoints | Additional timepoints during the study, including 2 weeks after each vaccination and 12 weeks, 24 weeks, and 40 weeks after second vaccination | Function of CD8 T-cell responses to HIV-1 Mfuse1 at additional timepoints in participants who have a response in the primary assay |
| Phenotypic Profile of HIV-1 Mfuse1-Specific CD4 T-Cell Responses at Additional Timepoints | Additional timepoints during the study, including 2 weeks after each vaccination and 12 weeks, 24 weeks, and 40 weeks after second vaccination. | Characteristics of CD4 T cells that respond to HIV-1 Mfuse1 at additional timepoints in participants who have a response in the primary assay |
| Phenotypic Profile of HIV-1 Mfuse1-Specific CD8 T-Cell Responses at Additional Timepoints | Additional timepoints during the study, including 2 weeks after each vaccination and 12 weeks, 24 weeks, and 40 weeks after second vaccination | Characteristics of CD8 T cells that respond to HIV-1 Mfuse1 at additional timepoints in participants who have a response in the primary assay |
Countries
United States
Outcome results
None listed