Evaluating the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Moderna Inc.

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

3 Feb 2022 → 5 Nov 2025

Decision date (initial)

2024-02-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-508820-37-00

EudraCT number

2020-006051-17

ClinicalTrials.gov

NCT05085366

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others

• 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.

Secondary objectives 1

1. • 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. • To demonstrate the efficacy of mRNA-1647 to prevent systemic viral dissemination in participants who meet the endpoint of CMV seroconversion. • To evaluate the efficacy of mRNA-1647 to reduce the frequency of urinary CMV shedding in CMV-seronegative participants meeting the endpoint of seroconversion due to primary CMV infection.

Conditions and MedDRA coding

Cytomegalovirus Infection (CMV)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products, Paul-Ehrlich-Institut, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 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 IgGnegative and CMV immunoglobulin M (IgM)-negative; For CMVseropositive 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. 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.

Exclusion criteria 2

1. 1-9: 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 primary vaccination series must have been completed a minimum of 28 days prior to receiving any dose of the study injection. - COVID-19 vaccines (including any booster dose, 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.
2. 10-10: 10. Is a member of study team or is an immediate family member or household member of study personnel.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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.

Secondary endpoints 3

1. •Antigen-specific nAb and binding antibody GMTs or GMCs on Day 1, Month 3, Month 7, and Month 12. •Antigen-specific nAb and binding antibody GMTs or GMCs on Month 18, Month 24, and Month 30.
2. • Systemic viral dissemination defined as seroconversion as described in the primary efficacy endpoint AND meeting one of the following PCR criteria during the post seroconversion period: a) Positive CMV PCR results in both blood and urine (concurrently or at different timepoints) OR b) Positive CMV PCR results in urine at ≥2 timepoints
3. • CMV PCR results in urine at each post seroconversion timepoint and during the entire post-seroconversion period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Moderna Inc.

Sponsor organisation

Moderna Inc.

Address

325 Binney Street

City

Cambridge

Postcode

02142-1038

Country

United States

Scientific contact point

Organisation

Moderna Therapeutics Inc.

Contact name

Moderna WeCare Team

Public contact point

Organisation

Moderna Therapeutics Inc.

Contact name

Moderna WeCare Team

Third parties 22

Locations

7 EU/EEA countries · 47 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 240 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications