E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cytomegalovirus infection (CMVi) |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of cytomegalovirus infection in healthy females between 16 and 35 years of age |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10009703 |
E.1.2 | Term | CMV infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To demonstrate the efficacy of a 3-dose regimen of V160 in reducing the incidence of primary CMVi during the follow-up period after the last dose of the vaccine
2. To assess the safety and tolerability of a 2-dose and a 3-dose regimen of V160 |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the efficacy of a 2-dose regimen of V160 in reducing the incidence of primary CMVi during the follow-up period after the last dose of the vaccine |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Merck will conduct Future Biomedical Research on DNA (Blood), saliva and urine specimens collected during this clinical trial. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time |
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E.3 | Principal inclusion criteria |
1) Healthy, based on medical history and physical examination
2) Female, 16 to 35 years of age
3) Serologically confirmed as CMV seronegative (based on CMV IgG) prior to receiving the first dose of V160/placebo
4) Have direct exposure to young children (<=5 years of age) at home or occupationally
5) Childbearing potential
6) Agrees to avoid becoming pregnant during the 6-month treatment phase and for 4 weeks after the last dose of V160/placebo (from Day 1 through Month 7) by either practicing abstinence from heterosexual activity OR by using allowable methods of birth control during heterosexual activity.
7) Voluntarily agrees to participate (or legally acceptable representative, for minors, if applicable); and provide written informed consent/assent for the trial. The participant may also provide consent/assent for Future Biomedical Research. However the participant may participate in the main trial without participating in Future Biomedical Research
8) Be able to complete all scheduled visits and to comply with the study procedures
9) Agrees to provide study personnel with a primary telephone number as well as an alternate form of contact, if available, for follow-up purposes |
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E.4 | Principal exclusion criteria |
1. 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
2. Has a history of any allergic reaction or an anaphylactic/anaphylactoid reaction to any vaccination that required medical intervention, or of any severe allergic reaction (eg, swelling of the mouth and throat, difficulty breathing, hypotension, or shock), to any vaccine component that required medical intervention
3. Has a recent (<72 hours) history of febrile illness (temperature ≥100.4°F/38.0°C, oral equivalent)
4. Is currently immunocompromised or has been diagnosed as having a congenital or acquired immunodeficiency, human immunodeficiency virus (HIV) infection, lymphoma, or leukemia. Participants with autoimmune conditions that require immunosuppressive medications (e.g, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease) are also to be excluded. No testing for HIV will be required in the study
5. Has a condition in which repeated venipuncture or injections pose more than minimal risk for the participant, such as hemophilia, thrombocytopenia, other severe coagulation disorders, or significantly impaired venous access
6. 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. If the urine test on the day of vaccination cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. If pregnancy is diagnosed any time after the first dose but before the completion of the vaccination series, the participant is excluded from any remaining vaccinations but is included in the study for safety follow-up
7. Has previously received a CMV vaccine
8. 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
9. Had any inactivated vaccine administered or scheduled within the period from 14 days prior to, through 14 days following, any dose of trial vaccine
10. Had administration of any immune globulin or blood product within 90 days prior to injection with V160/placebo or scheduled within 30 days thereafter
11. Has 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
12. Has 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)
13. Has 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. Anti-viral agents prohibited include letermovir, ganciclovir, valganciclovir, foscarnet, cidofovir, and valacyclovir.
14. Is receiving or has received in the year prior to enrollment immunosuppressive therapies including but not limited to rapamycin (also sirolimus), tacrolimus (also FK-506 or Fujimycin), 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
15. Has 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. (Participation in a safety surveillance or non-interventional trial is acceptable)
16. Planned donation of eggs at any time from signing the informed consent through 1 month after receiving the last dose of the trial V160/placebo
17. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling or child) who is investigational site or sponsor staff directly involved with this study
18. Any other reason that in the opinion of the investigator might interfere with the evaluation required by the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Efficacy: number of participants with CMVi in the V160 3- dose regimen and placebo arms
2. Safety: number of participants experiencing solicited injection site AEs within Days 1 through 5 after each vaccination visit; solicited systemic AEs and vaccine related serious AEs within Days 1 through 14 after each vaccination visit |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Analysis is endpoint-driven. An interim analysis (IA) for the purpose of testing the primary efficacy hypothesis will be conducted upon accrual of a total of 15 CMVi endpoint cases. It is anticipated that the required 15 cases will be accumulated at ≈18 months after enrollment of the first study participant. |
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E.5.2 | Secondary end point(s) |
Efficacy: number of participants with CMVi in the V160 2-dose regimen and placebo arms |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
There is only one final analysis of the secondary efficacy endpoint. However, the testing of the secondary efficacy hypothesis may occur at the time of the IA or the final analysis of the primary efficacy hypothesis. The secondary efficacy hypothesis will only be tested if the primary efficacy hypothesis is successfully demonstrated. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Israel |
Russian Federation |
United States |
Finland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The overall study ends when the last participant completes the last study- related contact or visit, withdraws from the study or is lost to follow-up (i.e, the participant is unable to be contacted by the investigator). For purposes of analysis and reporting, the overall study ends when the sponsor receives the last laboratory result or at the time of final contact with the last participant, whichever comes last. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |