Clinical trial NCT03486834: V160 2-Dose and 3-Dose Regimens in Healthy Cytomegalovirus (CMV) Seronegative Females (V160-002)
Official title: Double-Blind, Randomized, Placebo-Controlled Phase 2b, Multi-center Study to Evaluate the Safety, Tolerability, Efficacy and Immunogenicity of a 2-Dose and a 3-Dose Regimen of V160 (Cytomegalovirus [CMV] Vaccine) in Healthy Seronegative Women, 16 to 35 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus (CMV) Infections
Keywords: Prevention of cytomegalovirus infection (CMVi)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-04-03
Enrollment: 2200
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study evaluated the safety, tolerability, and efficacy of the cytomegalovirus (CMV) vaccine (V160) administered in a 2-dose or 3-dose regimen to healthy seronegative women 16 to 35 years of age. Participants received blinded V160 on Day 1, Month 2, and Month 6 (3-dose regimen), V160 on Day 1 and Month 6 and placebo at Month 2 (2-dose regimen), or placebo on Day 1, Month 2, and Month 6, and were followed to approximately Month 24. The primary hypothesis of the study was that administration of a 3-dose regimen of V160 will reduce the incidence of primary CMV infection compared to placebo.


Eligibility criteria: Inclusion Criteria:

* Healthy based on medical history and physical examination.
* Serologically confirmed to be CMV seronegative prior to receiving the first dose of V160/placebo
* Have direct exposure to young children (≤5 years of age) at home or occupationally
* Of childbearing potential
* Agrees to avoid becoming pregnant during the 6-month treatment period and for at least 4 weeks after the last dose of study drug by either 1) practicing abstinence from heterosexual activity, or 2) use a highly-effective method of birth control (as specified in the protocol) during heterosexual activity.

Exclusion Criteria:

* Has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might expose the participant to risk by participating in the trial, confound the results of the trial, or interfere with participation for the full duration of the trial, as assessed by the investigator
* Has history of allergic reaction or anaphylactic reaction to any vaccine component that required medical intervention or of any severe allergic reaction to any vaccine component that required medical intervention.
* Has a recent (\<72 hours) history of febrile illness (temperature ≥100.4°F/38.0°C, oral equivalent)
* Is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, or other autoimmune condition that requires immunosuppressive medication.
* Has a condition in which repeated venipuncture or injections pose more than minimal risk for the participant.
* A woman of childbearing potential (WOCBP) who has a positive pregnancy test at screening or within 24 hours before the first dose of study treatment.
* Has previously received a CMV vaccine.
* Had any live virus vaccine administered or scheduled to be administered in the period from 4 weeks prior to, and 4 weeks following receipt of any dose of trial vaccine.
* Had any inactivated vaccine administered or scheduled within the period from 14 days prior to, through 14 days following, any dose of trial vaccine.
* Had administration of any immune globulin or blood product within 90 days prior to injection with V160/placebo or scheduled within 30 days thereafter.
* Received systemic corticosteroids (equivalent of ≥2 mg/kg total daily dose of prednisone or ≥20 mg/d for persons weighing \>10 kg) for ≥14 consecutive days and has not completed treatment at least 30 days prior to trial entry.
* Received systemic corticosteroids exceeding physiologic replacement doses (≈5 mg/d prednisone equivalent) within 14 days prior to the first vaccination (participants using inhaled, nasal, or topical steroids are considered eligible for the trial).
* Received any anti-viral agent with proven or potential activity against CMV two weeks prior to vaccination or is likely to receive such an agent within 2 weeks after vaccination.
* Receiving or has received in the year prior to enrollment immunosuppressive therapies or other therapies used for solid organ/cell transplant, radiation therapy, immunosuppressive/cytotoxic immunotherapy, chemotherapy and other immunosuppressive therapies known to interfere with the immune response. Topical tacrolimus is allowed provided that it is not used within 2 weeks prior to, or 2 weeks following a V160 dose.
* Participated in another clinical trial in the past 4 weeks, or plans to participate in a treatment-based trial or a trial in which an invasive procedure is to be performed while enrolled in this trial.
* Plans donation of eggs at any time from signing the informed consent through 1 month after receiving the last dose of the trial V160/placebo.

Primary outcomes:
measure: Number of Participants Who Became Infected With Wild-Type Cytomegalovirus Infection Starting at 4 Weeks Post Last Dose (V160 3-dose Regimen Group and Placebo Group)
timeFrame: 4 weeks post last vaccination (Month 7) up to ~Month 24
measure: Number of Participants With Solicited Injection-site Adverse Events
timeFrame: Up to 5 days after each vaccination
measure: Number of Participants With Solicited Systemic AEs
timeFrame: Up to 14 days after each vaccination
measure: Number of Participants With Vaccine-related Serious Adverse Events
timeFrame: Up to 14 days after each vaccination
Secondary outcomes:
measure: Number of Participants Who Became Infected With Wild-Type CMV Infection Starting at 4 Weeks Post Last Dose (V160 2-dose Regimen Group and Placebo Group)
timeFrame: 4 weeks post last vaccination (Month 7) up to ~Month 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics ( Site 0025)
state: Alabama
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC ( Site 0055)
state: Alabama
city: Chandler
country: United States
facility: Synexus US Phoenix Southeast ( Site 0057)
state: Arizona
city: Rialto
country: United States
facility: Inland Empire Liver Foundation ( Site 0026)
state: California
city: Riverside
country: United States
facility: Integrated Research of Inland, Inc. ( Site 0042)
state: California
city: San Diego
country: United States
facility: California Research Foundation ( Site 0286)
state: California
city: Valley Village
country: United States
facility: Bayview Research Group, LLC ( Site 0012)
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc ( Site 0009)
state: California
city: Washington
country: United States
facility: Emerson Clinical Research Institute ( Site 0297)
state: District of Columbia
city: Coral Gables
country: United States
facility: Clinical Research of South Florida ( Site 0047)
state: Florida
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc ( Site 0007)
state: Florida
city: Hialeah
country: United States
facility: NF Research Center LLC ( Site 0013)
state: Florida
city: Hialeah
country: United States
facility: Best Quality Research Inc. ( Site 0031)
state: Florida
city: Jacksonville
country: United States
facility: Care Partners Clinical Research, LLC ( Site 0002)
state: Florida
city: Miami
country: United States
facility: L&C Professional Medical Research Institute ( Site 0021)
state: Florida
city: Miami
country: United States
facility: Advanced Medical Research Institute ( Site 0296)
state: Florida
city: Miami
country: United States
facility: Kendall South Medical Center, Inc ( Site 0008)
state: Florida
city: Miami
country: United States
facility: New Age Medical Research Corporation ( Site 0018)
state: Florida
city: Orlando
country: United States
facility: Clinical Associates of Orlando, LLC ( Site 0032)
state: Florida
city: Columbus
country: United States
facility: Columbus Regional Research Institute ( Site 0298)
state: Georgia
city: Augusta
country: United States
facility: Heartland Research Associates, LLC ( Site 0044)
state: Kansas
city: Newton
country: United States
facility: Heartland Research Associates, LLC ( Site 0023)
state: Kansas
city: Wichita
country: United States
facility: Heartland Research Associates, LLC ( Site 0019)
state: Kansas
city: Haughton
country: United States
facility: ACC Pediatric Research ( Site 0022)
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine ( Site 0041)
state: Maryland
city: Newark
country: United States
facility: St Michaels Med Center ( Site 0285)
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials ( Site 0052)
state: New Mexico
city: New Windsor
country: United States
facility: Mid Hudson Medical Research ( Site 0294)
state: New York
city: Durham
country: United States
facility: Carolina Women's Research and Wellness Center ( Site 0035)
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh, LLC ( Site 0048)
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington ( Site 0006)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center ( Site 0003)
state: Ohio
city: Cleveland
country: United States
facility: Senders Pediatrics ( Site 0060)
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc. ( Site 0038)
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute ( Site 0287)
state: Oklahoma
city: Charleston
country: United States
facility: Coastal Pediatric Research ( Site 0010)
state: South Carolina
city: Greenville
country: United States
facility: Parkside Pediatric ( Site 0288)
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center ( Site 0053)
state: South Carolina
city: Summerville
country: United States
facility: Palmetto Clinical Research ( Site 0289)
state: South Carolina
city: Austin
country: United States
facility: Tekton Research, Inc. ( Site 0036)
state: Texas
city: Corpus Christi
country: United States
facility: Coastal Bend Clinical Research ( Site 0299)
state: Texas
city: Dallas
country: United States
facility: Radiant Research - Dallas ( Site 0045)
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston ( Site 0049)
state: Texas
city: Houston
country: United States
facility: Juno Research, LLC ( Site 0293)
state: Texas
city: Pasadena
country: United States
facility: Accurate Clinical Management, LLC ( Site 0028)
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group ( Site 0001)
state: Texas
city: San Antonio
country: United States
facility: Synexus Research ( Site 0058)
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research LLC ( Site 0283)
state: Texas
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc. ( Site 0014)
state: Virginia
city: Norfolk
country: United States
facility: Clinical Research Associates of Tidewater ( Site 0056)
state: Virginia
city: Norfolk
country: United States
facility: York Clinical Research, LLC ( Site 0033)
state: Virginia
city: Richmond
country: United States
facility: National Clinical Research-Richmond, Inc. ( Site 0051)
state: Virginia
city: Spokane
country: United States
facility: Multicare / Rockwood Clinic ( Site 0034)
state: Washington
city: Spokane
country: United States
facility: Premier Clinical Research Group ( Site 0050)
state: Washington
city: Blacktown
country: Australia
facility: Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 0247)
state: New South Wales
city: Kanwal
country: Australia
facility: Paratus Clinical Kanwal - Trial Clinic ( Site 0243)
state: New South Wales
city: Sydney
country: Australia
facility: Holdsworth House Medical Practice ( Site 0241)
state: New South Wales
city: Morayfield
country: Australia
facility: University of the Sunshine Coast Clinical Trials Centre ( Site 0244)
state: Queensland
city: Sippy Downs
country: Australia
facility: University of the Sunshine Coast Clinical Trials Centre ( Site 0245)
state: Queensland
city: Vancouver
country: Canada
facility: Vaccine Evaluation Center ( Site 0264)
state: British Columbia
city: Toronto
country: Canada
facility: PrimeHealth Clinical Research ( Site 0070)
state: Ontario
city: Montreal
country: Canada
facility: Clinique OVO ( Site 0067)
state: Quebec
city: Pierrefonds
country: Canada
facility: McGill University Health Centre - Vaccine Study Centre ( Site 0064)
state: Quebec
city: Sherbrooke
country: Canada
facility: Diex Recherche Sherbrooke Inc. ( Site 0066)
state: Quebec
city: Victoriaville
country: Canada
facility: Diex Recherche Victoriaville Inc. ( Site 0068)
state: Quebec
city: Quebec
country: Canada
facility: CHUQ - Unite de Recherche en Sante Publique ( Site 0065)
city: Quebec
country: Canada
facility: Diex Recherche Quebec Inc ( Site 0069)
city: Espoo
country: Finland
facility: Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0186)
city: Helsinki
country: Finland
facility: Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0188)
city: Helsinki
country: Finland
facility: Ita-Helsingin Rokotetutkimuskeskus ( Site 0184)
city: Jarvenpaa
country: Finland
facility: Jarvenpaan rokotetutkimuskeskus ( Site 0185)
city: Kokkola
country: Finland
facility: Tampereen yliopisto Kokkolan rokotetutkimusklinikka ( Site 0190)
city: Oulu
country: Finland
facility: Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0187)
city: Pori
country: Finland
facility: Pori Vaccine Research Center ( Site 0182)
city: Seinajoki
country: Finland
facility: Seinajoki Vaccine Research Center ( Site 0189)
city: Tampere
country: Finland
facility: Tampereen yliopisto Rokotetutkimuskeskus ( Site 0181)
city: Turku
country: Finland
facility: Turku Vaccine Research Center ( Site 0183)
city: Haifa
country: Israel
facility: Rambam Medical Center - Health Care Campus ( Site 0219)
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical Center ( Site 0216)
city: Kfar Saba
country: Israel
facility: Meir MC ( Site 0213)
city: Nahariya
country: Israel
facility: Western Galilee Hospital ( Site 0212)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center ( Site 0218)
city: Sakhnin
country: Israel
facility: Sakhnin west neighbourhood ( Site 0211)
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center ( Site 0217)
city: Tel Aviv
country: Israel
facility: Maccabi Healthcare Services ( Site 0220)
city: Ekaterinburg
country: Russian Federation
facility: Central City Hospital 7 ( Site 0237)
city: Kazan
country: Russian Federation
facility: Limited Liability Company Medical Centre Aibolit ( Site 0229)
city: Kazan
country: Russian Federation
facility: LLC Scientific Research Medical Complex Your Health. ( Site 0230)
city: Moscow
country: Russian Federation
facility: City Clinical Hospital 13 of Moscow ( Site 0232)
city: Saint Petersburg
country: Russian Federation
facility: Antenatal clinic #22 ( Site 0225)
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University ( Site 0231)
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona ( Site 0155)
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre ( Site 0152)
city: Madrid
country: Spain
facility: Hospital Universitario La Paz ( Site 0157)
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitario de Santiago ( Site 0151)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Das R, Blazquez-Gamero D, Bernstein DI, Gantt S, Bautista O, Beck K, Conlon A, Rosenbloom DIS, Wang D, Ritter M, Arnold B, Annunziato P, Russell KL; V160-002 study group. Safety, efficacy, and immunogenicity of a replication-defective human cytomegalovirus vaccine, V160, in cytomegalovirus-seronegative women: a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Infect Dis. 2023 Dec;23(12):1383-1394. doi: 10.1016/S1473-3099(23)00343-2. Epub 2023 Aug 31.