Cytomegalovirus (CMV) Infections
Conditions
Keywords
Prevention of cytomegalovirus infection (CMVi)
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.
Interventions
BIOLOGICALV160
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.
DRUGPlacebo
Saline solution administered as a 0.5 mL IM injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 35 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 4 weeks post last vaccination (Month 7) up to ~Month 24 | 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. |
| Number of Participants With Solicited Injection-site Adverse Events | Up to 5 days after each vaccination | 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. |
| Number of Participants With Solicited Systemic AEs | Up to 14 days after each vaccination | 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. |
| Number of Participants With Vaccine-related Serious Adverse Events | Up to 14 days after each vaccination | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 4 weeks post last vaccination (Month 7) up to ~Month 24 | 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. |
Countries
Australia, Canada, Finland, Israel, Russia, Spain, United States
Participant flow
Pre-assignment details
A total of approximately 2100 participants were planned to be enrolled with 2200 participants actually randomized.
Participants by arm
| Arm | Count |
|---|---|
| V160 3-Dose Regimen Participants received V160 vaccination by intramuscular (IM) injection on Day 1, Month 2, and Month 6. | 733 |
| V160 2-Dose Regimen Participants received V160 vaccination by IM injection on Day 1 and Month 6 and placebo at Month 2. | 733 |
| Placebo Participants received placebo by IM injection on Day 1, Month 2, and Month 6. | 734 |
| Total | 2,200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 7 | 0 |
| Overall Study | Lost to Follow-up | 41 | 24 | 39 |
| Overall Study | Non-compliance with Study Drug | 2 | 2 | 0 |
| Overall Study | Physician Decision | 5 | 2 | 3 |
| Overall Study | Pregnancy | 10 | 12 | 12 |
| Overall Study | Protocol Deviation | 2 | 3 | 3 |
| Overall Study | Randomized but not treated | 4 | 4 | 1 |
| Overall Study | Withdrawal by Parent/Guardian | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 46 | 46 | 52 |
Baseline characteristics
| Characteristic | V160 3-Dose Regimen | V160 2-Dose Regimen | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 26.0 Years STANDARD_DEVIATION 5 | 26.1 Years STANDARD_DEVIATION 4.9 | 25.9 Years STANDARD_DEVIATION 4.9 | 26.0 Years STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 144 Participants | 145 Participants | 143 Participants | 432 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 588 Participants | 585 Participants | 587 Participants | 1760 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 7 Participants | 6 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 47 Participants | 49 Participants | 43 Participants | 139 Participants |
| Race (NIH/OMB) More than one race | 23 Participants | 23 Participants | 16 Participants | 62 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 657 Participants | 652 Participants | 665 Participants | 1974 Participants |
| Sex: Female, Male Female | 733 Participants | 733 Participants | 734 Participants | 2200 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 733 | 0 / 733 | 0 / 734 |
| other Total, other adverse events | 697 / 728 | 700 / 729 | 557 / 732 |
| serious Total, serious adverse events | 22 / 728 | 29 / 729 | 26 / 732 |
Outcome results
Primary
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.
Time frame: 4 weeks post last vaccination (Month 7) up to ~Month 24
Population: The analysis population included participants who were CMV seronegative at Day 1 and CMV negative by polymerase chain reaction (PCR) for nonvaccine strain virus from post Day 1 through Month 7, had received all 3 injections/vaccinations within the vaccination visit window, and did not have any deviations from protocol deemed to potentially interfere with the evaluation of efficacy or immune response to injection of V160.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V160 3-Dose Regimen | 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) | 14 Participants |
| Placebo | 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) | 24 Participants |
95% CI: [1.6, 4.9]
95% CI: [3.3, 7.6]
95% CI: [-13.5, 71.1]
Primary
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.
Time frame: Up to 5 days after each vaccination
Population: The analysis population included all randomized participants who received at least 1 injection of V160 or placebo, had safety follow-up data, and had been assigned to the treatment arm corresponding to the actual clinical material received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V160 3-Dose Regimen | Number of Participants With Solicited Injection-site Adverse Events | 683 Participants |
| Placebo | Number of Participants With Solicited Injection-site Adverse Events | 668 Participants |
| Placebo | Number of Participants With Solicited Injection-site Adverse Events | 249 Participants |
95% CI: [55.8, 63.5]
95% CI: [53.5, 61.5]
Primary
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.
Time frame: Up to 14 days after each vaccination
Population: The analysis population included all randomized participants who received at least 1 injection of V160 or placebo, had safety follow-up data, and had been assigned to the treatment arm corresponding to the actual clinical material received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V160 3-Dose Regimen | Number of Participants With Solicited Systemic AEs | 621 Participants |
| Placebo | Number of Participants With Solicited Systemic AEs | 633 Participants |
| Placebo | Number of Participants With Solicited Systemic AEs | 508 Participants |
95% CI: [11.7, 20.1]
95% CI: [13.3, 21.6]
Primary
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.
Time frame: Up to 14 days after each vaccination
Population: The analysis population included all randomized participants who received at least 1 injection of V160 or placebo, had safety follow-up data, and had been assigned to the treatment arm corresponding to the actual clinical material received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V160 3-Dose Regimen | Number of Participants With Vaccine-related Serious Adverse Events | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Serious Adverse Events | 0 Participants |
| Placebo | Number of Participants With Vaccine-related Serious Adverse Events | 0 Participants |
95% CI: [-0.5, 0.5]
95% CI: [-0.5, 0.5]
Secondary
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.
Time frame: 4 weeks post last vaccination (Month 7) up to ~Month 24
Population: The analysis population included participants who were CMV seronegative at Day 1 and CMV negative by polymerase chain reaction (PCR) for nonvaccine strain virus from post Day 1 through Month 7, had received all 2 injections/vaccinations within the vaccination visit window, and did not have any deviations from protocol deemed to potentially interfere with the evaluation of efficacy or immune response to injection of V160.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| V160 3-Dose Regimen | 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) | 31 Participants |
| Placebo | 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) | 24 Participants |
95% CI: [4.6, 9.5]
95% CI: [3.3, 7.6]
95% CI: [-135, 25]