Clinical trial NCT01986010: Safety, Tolerability, and Immunogenicity of the Human Cytomegalovirus Vaccine (V160) in Healthy Adults (V160-001)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cytomegalovirus Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-11-18
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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
* Has history within the past 5 years or current drug or alcohol abuse
* Has major psychiatric illness
* Is legally or mentally incapacitated
* Has participated in another clinical study in the past 4 weeks, or plans during the present study to participate in a treatment-based study or a study in which an invasive procedure is performed
* Has received valganciclovir, ganciclovir, valacyclovir, foscarnet, or cidofovir from 4 weeks prior to 1 month following each V160 vaccination

Primary outcomes:
measure: Percentage of Participants With an Adverse Event (AE)
timeFrame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
measure: Percentage of Participants With an Injection-site AE
timeFrame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
measure: Percentage of Participants With a Systemic AE
timeFrame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
measure: Percentage of Participants With a Serious Adverse Event (SAE)
timeFrame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
measure: Percentage of Participants With a Serious Vaccine-Related Adverse Event
timeFrame: Up to 2 weeks after vaccination on Day 1, Month 1 and Month 6 (up to Day 15, Week 6 and Week 26)
measure: Percentage of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to Month 6
measure: Percentage of Participants With Events of Clinical Interest (ECI)
timeFrame: Up to 18 months
measure: Geometric Mean Titer of HCMV-specific Neutralizing Antibody After Vaccination 3
timeFrame: Month 7 (1 month after vaccination 3 at Month 6)
Secondary outcomes:
measure: Geometric Mean Count of Peripheral Blood Mononuclear Cells Secreting Interferon-Gamma
timeFrame: Month 7 (1 month after vaccination 3 at Month 6)
measure: Geometric Mean Concentration of Interferon-Gamma After Stimulation of Whole Blood Sample With Pooled HCMV Antigen Peptides
timeFrame: Month 7 (1 month after vaccination 3 at Month 6)
measure: Geometric Mean Titer of HCMV-specific Neutralizing Antibody After Vaccinations 1 and 2
timeFrame: Month 1 and 2 (one month after vaccination 1 [Day 1] and vaccination 2 [Month 1])
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Cox KS, Zhang L, Freed DC, Tang A, Zhang S, Zhou Y, Wang IM, Rupp RE, Adler SP, Musey LK, Wang D, Vora KA, Fu TM. Functional Evaluation and Genetic Evolution of Human T-Cell Responses After Vaccination With a Conditionally Replication-Defective Cytomegalovirus Vaccine. J Infect Dis. 2021 Jun 4;223(11):2001-2012. doi: 10.1093/infdis/jiaa631.
citation: Adler SP, Lewis N, Conlon A, Christiansen MP, Al-Ibrahim M, Rupp R, Fu TM, Bautista O, Tang H, Wang D, Fisher A, Culp T, Das R, Beck K, Tamms G, Musey L; V160-001 Study Group. Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. J Infect Dis. 2019 Jul 2;220(3):411-419. doi: 10.1093/infdis/jiz141.