E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Cytomegalovirus infection |
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E.1.1.1 | Medical condition in easily understood language |
Prevention of Cytomegalovirus infection |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072247 |
E.1.2 | Term | Cytomegalovirus immunisation |
E.1.2 | System Organ Class | 10042613 - Surgical and medical procedures |
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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 |
* To demonstrate the efficacy of mRNA-1647 vaccine to prevent primary CMV infection in CMV-seronegative female participants * To evaluate the safety and reactogenicity of mRNA-1647 vaccine when administered on a 3-dose injection schedule in all participants. |
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E.2.2 | Secondary objectives of the trial |
* To evaluate immunogenicity to mRNA-1647 when administered on a 3-dose injection schedule in all participants. * To evaluate persistence of immunogenicity to mRNA-1647 through 24 months after the third injection in all participants. |
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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 |
"A Substudy of Infant Outcomes in Participants who Become Pregnant During Participation in mRNA-1647-P301." mRNA-1647-P301a Substudy is included in the Protocol. The aim of the substudy is to assess cytomegalovirus (CMV)-related outcomes in live births of female participants who become pregnant during the course of the mRNA-1647-P301 main study. All objectives and endpoints in this substudy are exploratory.
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E.3 | Principal inclusion criteria |
Inclusion Criteria Participants are eligible to be included in the study only if all the following criteria apply (no protocol exemptions will be allowed in this study): 1. Is a female and 16 to 40 years of age, at the time of consent. 2. According to the assessment of the Investigator, is capable of complying with study procedures. 3. For female participants aged ≥ 20 years, has or anticipates having direct exposure within 7 months after planned first dose (in the home, socially, or occupationally) to at least 1 child ≤ 5 years of age. Direct exposure is defined as either a) participant is the parent, or b) participant has close contact (feeding, diaper changes, childcare/supervision) for at least 8 hours per week. 4. For the CMV-seronegative Cohorts: at the Screening visit, is CMV IgG-negative and CMV immunoglobulin M (IgM)-negative; For CMV-seropositive Cohorts: at the Screening visit, is CMV IgG-positive and CMV IgMnegative, or CMV IgG-positive and CMV IgM-positive . Participants with an isolated positive result for CMV IgM (ie, CMV IgG-negative and CMV IgM-positive) will not be eligible for enrollment but may be rescreened after at least 6 weeks from the initial CMV screening. A participant with a CMV IgG-positive result and an IgM-indeterminate result at Screening will not require the IgM sampling to be repeated in order to consider the participant CMV-seropositive (Section 5.3). 5. Participants (and parent/LAR, if applicable) provides written informed consent/assent. Participants under the age of majority (ie, under legal age) at the time of enrollment must provide written informed consent at the next study visit once turning the age of majority. 6. Investigator assessment confirms that the participant (including in the case of an emancipated minor), or parent(s)/LAR(s), as applicable, understands and is willing and physically able to comply with protocol-mandated follow-up including all study visits and procedures anticipated during the 30-month study period. 7. This criterion has been removed in Protocol Amendment 2: Has a body mass index of 15-35 kg/m2, inclusive. 8. Female participants of childbearing potential: Urine pregnancy test is negative at Screening and negative on the day of the first injection (Day 1). Note: urine pregnancy test at Screening or Day 1 is not required for female participants of nonchildbearing potential. See Section 11.8 for definition of nonchildbearing potential. 9. Female participants of childbearing potential: If the participant is sexually active with men, all of the following criteria must be met: • Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1). • Agrees to continue adequate contraception through 3 months following the third study injection (Month 9/Day 257). Adequate contraception is defined as consistent and correct use of an approved contraceptive method in accordance with the product label, or sterilization of a monogamous male partner prior to study enrollment (Section 11.8.2). |
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E.4 | Principal exclusion criteria |
Exclusion Criteria Participants eligible for the study must not meet any of the following criteria: 1. This criterion has been removed in Protocol Amendment 2: Female participants: Is of nonchildbearing potential. Nonchildbearing potential is defined as one of the following: • Surgically sterile (reports history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy). • Postmenopausal state (reports history of amenorrhea for ≥ 12 consecutive months prior to Screening without an alternative medical cause). 2. History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures. Clinically unstable is defined as a diagnosis or condition requiring significant changes in management or medication within the 2 months prior to Screening, and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition. This includes but is not limited to: • Reported history of congenital or acquired immunodeficiency, immunosuppressive condition, or immune-mediated disease. • Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos; psoriasis patches affecting skin over the deltoid areas). • Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of the mRNA-1647 vaccine or any components of the mRNA-1647 vaccine. • Reported history of bleeding disorder that is considered a contraindication to intramusculary (IM) injection or phlebotomy. • Any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. 3. Received or plans to receive any non study vaccine < 28 days prior to and after any study injection; in addition, the following criteria for COVID-19 and influenza vaccines apply: - Any COVID-19 vaccination series must have been completed a minimum of 28 days prior to receiving any dose of the study injection. - COVID-19 vaccines (regardless of manufacturer) must be administered at least 28 days prior to or after any study injection. - Influenza vaccines may be administered > 14 days prior to or after any study injection. 4. Received systemic immunosuppressants or immune-modifying drugs for > 14 days in total within 6 months prior to the day of first injection (Day 1) (for corticosteroids, ≥ 5 mg/day of prednisone equivalent) or plans to do so during the course of the study. Inhaled, nasal, and topical steroids are allowed. Stable immunomodulator regimens used for managing environmental allergies are allowed. 5. Receipt of an antiviral with activity against CMV (ganciclovir, valganciclovir, foscarnet, cidofovir, letermovir, acyclovir, valacyclovir) < 2 weeks prior to the day of first injection or plans to do so during the course of the study. 6. Previous receipt of an investigational CMV vaccine. 7. Receipt of systemic immunoglobulins or blood products < 3 months prior to the day of first injection. 8. Has donated ≥ 450 mL of blood products < 28 days prior to Screening. 9. Participated in an interventional clinical study < 28 days prior to the day of first injection (Day 1) or plans to do so while enrolled in this study. 10. Is a member of study team or is an immediate family member or household member of study personnel. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Primary CMV infection, defined as seroconversion from a negative to a positive result for serum IgG as measured by a platform-based automated immunoassay based on at least 1 of the 4 recombinant CMV antigens not encoded by mRNA-1647 (pp150, pp28, pp52, pp38) assessed starting 28 days after the third injection. 2. Solicited ARs through 7 days after each injection, unsolicited AEs through 28 days after each injection, MAAEs from Day 1 through 6 months after the last injection, AESIs from Day 1 through EOS, and SAEs from time of consent through EOS.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Screening, Day 1, Day 57/M2, Day 85/M3, Day 169/M6, Day 197/M7, Day 287/M10, Day 347/M12, Day 437/M15, Day 527/M18, Day 617/M21, Day 707/M24, Day 797/M27, Day 887/M30 (EOS) Additional unscheduled study visits will be done if participants report symptoms in between scheduled study visits. 2. Solicited ARs through 7 days after each injection; Unsolicited AEs through 28 days after each injection, MAAEs from Day 1 through 6 months after the last injection, AESIs from Day 1 through EOS, and SAEs from time of consent through EOS; SAEs from time of consent through EOS. AEs leading to withdrawal/study discontinuation – from Day 1 through EOS. |
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E.5.2 | Secondary end point(s) |
* Antigen-specific nAb and binding antibody GMTs on Day 1, Month 3, Month 7, and Month 12. * Antigen-specific nAb and binding antibody GMTs on Month 18, Month 24, and Month 30. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Day 1, Day 85/M3, Day 197/M7 and Day 347/M12 2. Day 527/M18, Day 707/M24, and Day 887/M30 (EOS) |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 |
Australia |
Canada |
Israel |
Japan |
United States |
Estonia |
Finland |
France |
Spain |
Germany |
Italy |
Belgium |
United Kingdom |
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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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
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 | 4 |
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 |