V160 2-Dose and 3-Dose Regimens in Healthy Cytomegalovirus (CMV) Seronegative Females (V160-002)

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

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus (CMV) Infections
• Intervention / Treatment: Biological: V160; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 2200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 0247)
    • Kanwal, New South Wales, Australia, 2259
      • Paratus Clinical Kanwal - Trial Clinic ( Site 0243)
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice ( Site 0241)
  • Queensland
    • Morayfield, Queensland, Australia, 4506
      • University of the Sunshine Coast Clinical Trials Centre ( Site 0244)
    • Sippy Downs, Queensland, Australia, 4556
      • University of the Sunshine Coast Clinical Trials Centre ( Site 0245)
• Canada
  • Quebec, Canada, G1E 7G9
    • CHUQ - Unite de Recherche en Sante Publique ( Site 0065)
  • Quebec, Canada, G1N 4V3
    • Diex Recherche Quebec Inc ( Site 0069)
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • Vaccine Evaluation Center ( Site 0264)
  • Ontario
    • Toronto, Ontario, Canada, M4S 1Y2
      • PrimeHealth Clinical Research ( Site 0070)
  • Quebec
    • Montreal, Quebec, Canada, H4P 2S4
      • Clinique OVO ( Site 0067)
    • Pierrefonds, Quebec, Canada, H9H 4Y6
      • McGill University Health Centre - Vaccine Study Centre ( Site 0064)
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke Inc. ( Site 0066)
    • Victoriaville, Quebec, Canada, G6P 6P6
      • Diex Recherche Victoriaville Inc. ( Site 0068)
• Finland
  • Espoo, Finland, 02230
    • Tampereen yliopisto Espoon rokotetutkimusklinikka ( Site 0186)
  • Helsinki, Finland, 00100
    • Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 0188)
  • Helsinki, Finland, 00930
    • Ita-Helsingin Rokotetutkimuskeskus ( Site 0184)
  • Jarvenpaa, Finland, 04400
    • Jarvenpaan rokotetutkimuskeskus ( Site 0185)
  • Kokkola, Finland, 67100
    • Tampereen yliopisto Kokkolan rokotetutkimusklinikka ( Site 0190)
  • Oulu, Finland, 90220
    • Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 0187)
  • Pori, Finland, 28100
    • Pori Vaccine Research Center ( Site 0182)
  • Seinajoki, Finland, 60100
    • Seinajoki Vaccine Research Center ( Site 0189)
  • Tampere, Finland, 33100
    • Tampereen yliopisto Rokotetutkimuskeskus ( Site 0181)
  • Turku, Finland, 20520
    • Turku Vaccine Research Center ( Site 0183)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center - Health Care Campus ( Site 0219)
  • Jerusalem, Israel, 9112001
    • Hadassah Ein Kerem Medical Center ( Site 0216)
  • Kfar Saba, Israel, 4428164
    • Meir MC ( Site 0213)
  • Nahariya, Israel, 2222214
    • Western Galilee Hospital ( Site 0212)
  • Petah-Tikva, Israel, 4941492
    • Rabin Medical Center ( Site 0218)
  • Sakhnin, Israel, 3081000
    • Sakhnin west neighbourhood ( Site 0211)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center ( Site 0217)
  • Tel Aviv, Israel, 6789140
    • Maccabi Healthcare Services ( Site 0220)
• Russian Federation
  • Ekaterinburg, Russian Federation, 620137
    • Central City Hospital 7 ( Site 0237)
  • Kazan, Russian Federation, 420073
    • Limited Liability Company Medical Centre Aibolit ( Site 0229)
  • Kazan, Russian Federation, 420097
    • LLC Scientific Research Medical Complex Your Health. ( Site 0230)
  • Moscow, Russian Federation, 115280
    • City Clinical Hospital 13 of Moscow ( Site 0232)
  • Saint Petersburg, Russian Federation, 194354
    • Antenatal clinic #22 ( Site 0225)
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University ( Site 0231)
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona ( Site 0155)
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre ( Site 0152)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0157)
  • Santiago de Compostela, Spain, 15706
    • Hospital Clinico Universitario de Santiago ( Site 0151)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Alabama Clinical Therapeutics ( Site 0025)
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC ( Site 0055)
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus US Phoenix Southeast ( Site 0057)
  • California
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation ( Site 0026)
    • Riverside, California, United States, 92506
      • Integrated Research of Inland, Inc. ( Site 0042)
    • San Diego, California, United States, 92123
      • California Research Foundation ( Site 0286)
    • Valley Village, California, United States, 91607
      • Bayview Research Group, LLC ( Site 0012)
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc ( Site 0009)
  • District of Columbia
    • Washington, District of Columbia, United States, 20011
      • Emerson Clinical Research Institute ( Site 0297)
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida ( Site 0047)
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc ( Site 0007)
    • Hialeah, Florida, United States, 33012
      • NF Research Center LLC ( Site 0013)
    • Hialeah, Florida, United States, 33016
      • Best Quality Research Inc. ( Site 0031)
    • Jacksonville, Florida, United States, 32277
      • Care Partners Clinical Research, LLC ( Site 0002)
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute ( Site 0021)
    • Miami, Florida, United States, 33174
      • Advanced Medical Research Institute ( Site 0296)
    • Miami, Florida, United States, 33185
      • Kendall South Medical Center, Inc ( Site 0008)
    • Miami, Florida, United States, 33186
      • New Age Medical Research Corporation ( Site 0018)
    • Orlando, Florida, United States, 32806
      • Clinical Associates of Orlando, LLC ( Site 0032)
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute ( Site 0298)
  • Kansas
    • Augusta, Kansas, United States, 67010
      • Heartland Research Associates, LLC ( Site 0044)
    • Newton, Kansas, United States, 67114
      • Heartland Research Associates, LLC ( Site 0023)
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates, LLC ( Site 0019)
  • Louisiana
    • Haughton, Louisiana, United States, 71037
      • ACC Pediatric Research ( Site 0022)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland School of Medicine ( Site 0041)
  • New Jersey
    • Newark, New Jersey, United States, 07102
      • St Michaels Med Center ( Site 0285)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials ( Site 0052)
  • New York
    • New Windsor, New York, United States, 12553
      • Mid Hudson Medical Research ( Site 0294)
  • North Carolina
    • Durham, North Carolina, United States, 27713
      • Carolina Women's Research and Wellness Center ( Site 0035)
    • Raleigh, North Carolina, United States, 27609
      • PMG Research of Raleigh, LLC ( Site 0048)
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington ( Site 0006)
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center ( Site 0003)
    • Cleveland, Ohio, United States, 44121
      • Senders Pediatrics ( Site 0060)
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research, Inc. ( Site 0038)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute ( Site 0287)
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research ( Site 0010)
    • Greenville, South Carolina, United States, 29607
      • Parkside Pediatric ( Site 0288)
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center ( Site 0053)
    • Summerville, South Carolina, United States, 29485
      • Palmetto Clinical Research ( Site 0289)
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research, Inc. ( Site 0036)
    • Corpus Christi, Texas, United States, 78413
      • Coastal Bend Clinical Research ( Site 0299)
    • Dallas, Texas, United States, 75234
      • Radiant Research - Dallas ( Site 0045)
    • Galveston, Texas, United States, 77555-1115
      • University of Texas Medical Branch at Galveston ( Site 0049)
    • Houston, Texas, United States, 77074
      • Juno Research, LLC ( Site 0293)
    • Pasadena, Texas, United States, 77504
      • Accurate Clinical Management, LLC ( Site 0028)
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group ( Site 0001)
    • San Antonio, Texas, United States, 78229
      • Synexus Research ( Site 0058)
    • Victoria, Texas, United States, 77901
      • Crossroads Clinical Research LLC ( Site 0283)
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc. ( Site 0014)
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater ( Site 0056)
    • Norfolk, Virginia, United States, 23510
      • York Clinical Research, LLC ( Site 0033)
    • Richmond, Virginia, United States, 23294
      • National Clinical Research-Richmond, Inc. ( Site 0051)
  • Washington
    • Spokane, Washington, United States, 99202
      • Multicare / Rockwood Clinic ( Site 0034)
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research Group ( Site 0050)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 31 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V160 3-Dose Regimen; Participants received 3 doses of vaccine V160 (100 Units/0.5 mL dose with Merck aluminum phosphate adjuvant [MAPA], 4°C stable formulation) administered by intramuscular (IM) injection on Day 1, Month 2, and Month 6.	Biological: V160; V160 was administered as a 0.5 mL (100 Units/0.5 mL dose with Merck aluminum phosphate adjuvant [MAPA], 4°C stable formulation) IM injection.; Other Names: Human cytomegalovirus vaccine
Experimental: V160 2-Dose Regimen; Participants received 2 doses of vaccine V160 (100 Units/0.5 mL dose with MAPA, 4°C stable formulation) administered IM on Day 1 and Month 6 and a placebo-saline solution at Month 2.	Biological: V160; V160 was administered as a 0.5 mL (100 Units/0.5 mL dose with Merck aluminum phosphate adjuvant [MAPA], 4°C stable formulation) IM injection.; Other Names: Human cytomegalovirus vaccine; Drug: Placebo; Saline solution administered as a 0.5 mL IM injection
Placebo Comparator: Placebo; Participants received placebo (saline solution) by IM injection on Day 1, Month 2, and Month 6.	Drug: Placebo; Saline solution administered as a 0.5 mL IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Cytomegalovirus infection (CMVi) was defined as the detection of wild-type cytomegalovirus (CMV) (non vaccine type) by polymerase chain reaction in a single saliva or urine sample in a previously CMV-uninfected participant. CMVi cases in the 3-dose regimen and placebo groups were reported and incidence rate (per 100 person-years) calculated based on follow-up time starting at 4 weeks post last dose (Month 7) through approximately Month 24 (or time point to reach required cases for assessment). The percent reduction in CMVi incidence rate in the 3-dose regimen group compared to the placebo group was assessed.	4 weeks post last vaccination (Month 7) up to ~Month 24
Number of Participants With Solicited Injection-site Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. Following vaccination with V160 or placebo, the number of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, swelling, and pain.	Up to 5 days after each vaccination
Number of Participants With Solicited Systemic AEs	An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. Following vaccination with V160 or placebo, the number of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were fatigue, joint pain/arthralgia, muscle pain/myalgia, and headache.	Up to 14 days after each vaccination
Number of Participants With Vaccine-related Serious Adverse Events	A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator. Following vaccination with V160 or placebo, the number of participants with vaccine-related serious adverse events was assessed.	Up to 14 days after each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	CMVi is defined as detection of wild-type CMV (non-vaccine type) by polymerase chain reaction in a single saliva or urine sample in a previously CMV-uninfected participant. CMVi cases in the 2-dose regimen and placebo groups were reported and incidence rate (per 100 person-years) calculated based on follow-up time starting at 4 weeks post last dose (Month 7) through approximately Month 24 (or time point to reach required cases for assessment). The percent reduction in CMVi incidence rate in the 2-dose regimen group compared to the placebo group was assessed.	4 weeks post last vaccination (Month 7) up to ~Month 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2018
• Primary Completion (Actual): October 30, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: March 28, 2018
• First Submitted That Met QC Criteria: March 28, 2018
• First Posted (Actual): April 3, 2018

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 19, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Prevention of cytomegalovirus infection (CMVi)
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Herpesviridae Infections; Cytomegalovirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V160-002; 2017-004233-86 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No