A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity of the Human Cytomegalovirus Vaccine (V160) in Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Cytomegalovirus Infections
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 190
- Primary Endpoint
- Percentage of Participants With an Injection-site AE
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This study will evaluate the safety, tolerability, and immunogenicity of various doses, formulations, and routes of administration of Human Cytomegalovirus (HCMV) vaccine V160 administered in a 3-dose regimen in healthy adults. The initial treatment arm of HCMV seropositive participants will receive V160 Low Dose without adjuvant by intramuscular injection. Escalation of the V160 dose, inclusion of adjuvant, administration by intradermal injection, and vaccination of HCMV seronegative participants will be performed only after review of safety data of previous treatment arms. The purpose of the study is to identify vaccine formulations associated with optimal safety profile and HCMV-specific immune response for evaluation in subsequent clinical studies of V160.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy based on medical history and physical examination
- •Serologically confirmed to be HCMV seronegative or HCMV seropositive
- •Agrees to avoid unusual, unaccustomed strenuous, vigorous physical exercise/activity from 72 hours before through 72 hours after each dose of study vaccine
- •Body weight ≥110 lbs (50 kg) and body mass index (BMI) of 19 to 32 kg/m\^2
- •If of reproductive potential, agrees to the following during the study and for 4 weeks after the last dose of study vaccine: 1) practice abstinence from heterosexual activity, or 2) use or have their partner use 2 allowable methods of birth control during heterosexual activity
Exclusion Criteria
- •Has previously received any cytomegalovirus vaccine
- •Has history of allergic reaction or anaphylactic reaction to any vaccine component that required medical intervention
- •Has history of any severe allergic reaction that required medical intervention
- •Is pregnant or breastfeeding or expecting to conceive from 2 weeks before the study through 1 month after the last dose of study vaccine
- •Plans to donate eggs or sperm from study start through 1 month after the last dose of study drug
- •Has impairment of immunologic function including, but not limited to autoimmune disease, splenectomy, or human immunodeficiency virus acquired immunodeficiency syndrome (HIV/AIDS)
- •Received systemic corticosteroids for ≥14 consecutive days and has not completed treatment within 30 days of study start
- •Received immunosuppressive therapy including, but not limited to rapamycin and equivalents, tacrolimus, FK-506, fujimycin, or other therapies used for solid organ/cell transplant, radiation therapy, immunosuppressive/cytotoxic chemotherapy, or other therapy known to interfere with the immune response within 1 year of study start
- •Has a condition in which repeated venipuncture or injections pose more than minimal risk, such as hemophilia, thrombocytopenia or other severe coagulation disorders, or significantly impaired venous access
- •Has a condition that requires active medical intervention or monitoring such as diabetes mellitus, autoimmune disease, or a clinically significant chronic medical condition that is considered progressive
Outcomes
Primary Outcomes
Percentage of Participants With an Injection-site AE
Time Frame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
Injection-site AEs are defined as redness, swelling, and pain/tenderness.
Percentage of Participants With a Serious Adverse Event (SAE)
Time Frame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
A serious adverse event is any adverse event occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event
Percentage of Participants With a Systemic AE
Time Frame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
A Systemic AE includes, but is not exclusive of, the following AEs: fatigue, myalgia, headache and joint pain
Percentage of Participants With an Adverse Event (AE)
Time Frame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Percentage of Participants With a Serious Vaccine-Related Adverse Event
Time Frame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
A serious adverse event is any adverse event occurring at any dose or during any use of Sponsor's product that does the following: results in death; is life threatening; results in persistent or significant disability/incapacity; results in or prolongs an existing inpatient hospitalization; is a congenital anomaly/birth defect; is a cancer; is associated with an overdose; is another important medical event. A serious vaccine-related adverse event was determined by the investigator to be related to the vaccine.
Percentage of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: Up to Month 6
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol - specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Percentage of Participants With Events of Clinical Interest (ECI)
Time Frame: Up to 18 months
An event of clinical interest (ECI) is identified as any overdose, elevated liver values meeting threshold criteria (aspartate aminotransferase or alanine aminotransferase ≥3x upper limit of normal (ULN); total bilirubin ≥2x ULN, and, at the same time, alkaline phosphatase \<2xULN). Additionally, confirmed, diagnosed autoimmune conditions are considered ECIs.
Geometric Mean Titer of HCMV-specific Neutralizing Antibody After Vaccination 3
Time Frame: Month 7 (1 month after vaccination 3 at Month 6)
Serum samples for measuring neutralizing antibodies using the Merck Neutralizing Antibody (NAb) assay were collected at month 7. The LiCor-based near-infrared dye (NIRDye) In-Cell Western (ICW) HCMV microneutralization assay was used to detect and quantify anti-HCMV neutralizing antibodies. The primary hypothesis was that for HCMV-seronegative participants, at least 1 of the vaccination groups receiving V160 formulated with or without adjuvant would exhibit higher HCMV-specific neutralizing antibody titers than the placebo group.
Secondary Outcomes
- Geometric Mean Concentration of Interferon-Gamma After Stimulation of Whole Blood Sample With Pooled HCMV Antigen Peptides(Month 7 (1 month after vaccination 3 at Month 6))
- Geometric Mean Count of Peripheral Blood Mononuclear Cells Secreting Interferon-Gamma(Month 7 (1 month after vaccination 3 at Month 6))
- Geometric Mean Titer of HCMV-specific Neutralizing Antibody After Vaccinations 1 and 2(Month 1 and 2 (one month after vaccination 1 [Day 1] and vaccination 2 [Month 1]))