A study to investigate the reactogenicity, safety, and immunogenicity of mRNA-1345 in pregnant women, and safety and immunogenicity in their infants

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Moderna Inc.

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years, 18-64 years

Gender

Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

3 Sep 2024 → 25 May 2026

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

Maternal Participants-
To evaluate the reactogenicity and safety of mRNA-1345 administered during pregnancy.
Infant Participants:
- To evaluate the safety profile in infants born to women vaccinated with mRNA-1345 during pregnancy.

Secondary objectives 6

1. Maternal Participants: - To evaluate the immunogenicity of a single injection of mRNA-1345 in pregnant women.
2. Infant Participants: - To evaluate RSV antibody levels in infants born to women who receive a single mRNA-1345 injection during pregnancy
3. Maternal and Infant Participants: - To use exploratory assays for characterization of the immune response to vaccination with mRNA-1345.
4. Maternal Participants: - To evaluate the immunogenicity of mRNA-1345 with respect to breast milk.
5. To characterize cellular immunogenicity in a subset of participants.
6. Infant Participants: - To evaluate the efficacy of maternal vaccination with mRNA-1345 in preventing RSV disease.

Conditions and MedDRA coding

Respiratory syncytial virus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Participants are eligible to be included in the study only if all of the following criteria apply: Maternal Participants Age 1. Are adults ≥18 years to <40 years of age inclusive, at the time of signing the informed consent.
2. Informed Consent - Are willing and able (on both a physical and cognitive basis) to give written informed consent for themselves and their unborn child prior to study enrollment, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.* *Consent of the individual identified as the co-parent of the unborn child to be obtained in addition, if required by local regulations.
3. Infant Participants Informed Consent - Have consent from infant participant’s parent(s)/LAR(s) if required by local regulations.
4. Type of Participant and Disease Characteristics 2. Healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests
5. Will be 280/7 to 360/7 weeks pregnant at the time of vaccination (confirmed by an obstetric ultrasound report performed at 22 weeks or less; firsttrimester ultrasound is considered the gold standard for pregnancy dating). Details of the method for determination of the gestational age will be provided in the Study Operational Manual.
6. Intend to reside within a geographic area in which emergency pediatric care is provided by a study-affiliated site.
7. Intend to deliver at a maternity unit where study procedures can be performed.
8. Are willing and able to attend all study visits, to undergo all study procedures/or have their infant undergo all study procedures, and to comply with study requirements, including a means of communication (eg, phone, text message or email) with study site staff.
9. Give permission for study site staff to access their/or their infant’s relevant medical information from other healthcare facilities should healthcare be sought at nonstudy facilities postenrollment.
10. Have engaged with local antenatal care and will continue to do so through the remainder of their pregnancy.
11. Japanese women specific: Japanese participants are defined as individuals born in Japan, with both parents and 4 grandparents who were born in Japan.
12. Have consent from infant participant’s parent(s)/LAR(s) if required by local regulations.

Exclusion criteria 20

1. Maternal Participants Weight - Body mass index of ≥40 kg/m2 at time of the Screening Visit.
2. Have an infection with HIV, HBV, HCV, syphilis, or laboratory test results at the Screening Visit outside the normal reference value for pregnant women according to their trimester in pregnancy.
3. Have conditions in the current pregnancy that may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures, including but not limited to (refer to the Study Operational Manual for further details): a. Multiple pregnancies (eg, twins, triplets). b. Congenital malformation or clinically significant abnormalities on obstetric ultrasound. c. Congenital infection, including rubella, cytomegalovirus, toxoplasmosis, HSV (eg, primary genital HSV infection). d. Gestational hypertension, or preeclampsia. e. Antenatal hemorrhage. f. In-utero-growth restriction. g. Placental abnormality. h. Poly/oligohydramnios. i. Gestational diabetes. j. Pregnancy as a result of in vitro fertilization or other assisted reproductive technology. k. Threatened premature labor. l. Cervical insufficiency. m. Confirmed SARS-CoV-2 infection at any time during the pregnancy
4. Had conditions in previous pregnancies that may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures, including but not limited to (refer to the Study Operational Manual for further details): a. Stillbirth. b. Multiple (≥3) miscarriages. c. Cervical insufficiency. d. Grand multiparity (5 or greater previous pregnancies). e. Premature delivery (<34 weeks). f. Fetus or infant with known genetic disorder or congenital malformations. g. Preeclampsia. h. Gestational diabetes. i. Poly/oligohydramnios. j. D (Rhesus) sensitization.
5. Prior/Concomitant Therapy - Received or plans to receive any mRNA vaccine or COVID-19 vaccine within 4 weeks before or after Day 1 and/or any other nonstudy vaccine within 2 weeks before or after Day 1
6. Received systemic immunosuppressants for >14 consecutive days in total within 180 days prior to the Screening Visit (for corticosteroids, ≥10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, and topical steroids are allowed.
7. Previous vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.
8. Received blood or plasma products or immunoglobulin, from 60 days before study intervention administration, or planned receipt through delivery (excludes Rho[D)] immune globulin (eg, RhoGAM), which can be given at any time).
9. Prior/Concurrent Clinical Study Experience Participated in another clinical research study where participant has received a study intervention (drug/biologic/device) within 180 days before Day 1. Current or previous participation in another RSV investigational study is exclusionary.
10. Other Exclusion Criteria Is a study site staff or first-degree relatives/partners of study site staff.
11. Infant Participants. Is a child who has been placed under the control or protection of an agency, organization, institution, or entity by the courts, the government, or a government body acting in accordance with powers conferred on them by laws and regulation (eg, foster care). This does not include a child who is adopted or has an appointed LAR.
12. Medical Conditions - Acutely ill or febrile (temperature ≥38.0℃ [100.4°F]) within 72 hours prior to or at the Screening Visit or Day 1. See Section 5.3 for guidance on rescreening.
13. 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 60 days prior to Screening and includes ongoing workup of an undiagnosed illness that could lead to a new diagnosis or condition.
14. History of congenital or acquired immunodeficiency, immunosuppressive condition, asplenia, or recurrent severe infections
15. Dermatologic conditions that could affect local solicited AR assessments (eg, tattoos, psoriasis patches affecting skin over the deltoid areas).
16. Reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA vaccine or therapeutic or any components of an mRNA-1345 vaccine.
17. History of a bleeding disorder that is considered a contraindication to IM injection or phlebotomy
18. 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.
19. History of myocarditis, pericarditis, or myopericarditis, regardless of the timing of the past medical history.
20. Intend for their infant to receive RSV monoclonal antibodies after delivery.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Maternal Participants: • Solicited local and systemic adverse reactions through 7 days after study intervention. • Unsolicited adverse events through 28 days after study intervention. • Medically attended adverse events from Day 1 to Month 6 (6 months postdelivery).
2. Adverse events of special interest from Day 1 to Month 12 (12 months postdelivery)/EoS Visit. • Serious adverse events from Day 1 to Month 12 (12 months postdelivery)/EoS visit. • Adverse events leading to discontinuation from Day 1 to Month 12 (12 months postdelivery)/EoS Visit. • Pregnancy outcomes (mode and nature of delivery).
3. Infant Participants • Medically attended adverse events from Day 1 (birth) to Month 12/EoS Visit. • Adverse events of special interest from Day 1 (birth) to Month 12/EoS Visit. • Serious adverse events from Day 1 (birth) to Month 12/EoS Visit. • Birth outcomes (gestational age and anthropometric measurements)

Secondary endpoints 6

1. Maternal Participants: • GMT of serum RSV-A and RSV-B neutralizing antibody at Day 1, Day 29, delivery, and Month 6 (6 months postdelivery). • GMC of serum RSV-F binding antibody at Day 1, Day 29, delivery, and Month 6 (6 months postdelivery).
2. GMFR of Postbaseline/Baseline neutralizing antibody titers and binding antibody concentrations at Day 29, delivery, and Month 6 (6 months postdelivery). • Proportion of participants with ≥4-fold increases in neutralizing antibody titers and binding antibody concentrations from Baseline.
3. Infant Participants: • GMT of serum RSV-A and RSV-B neutralizing antibody at Day 1 (birth)a, and Months 2, 6, and 12. • GMC of serum RSV-F binding antibody at Day 1 (birth)a, and Months 2, 6, and 12.
4. Maternal and Infant Participants: • Additional markers of immune response to vaccination, including transcriptomic analysis.
5. RSV neutralizing and binding antibodies in breast milk. • Frequency, magnitude, and/or phenotype of vaccine-specific B-cell and T-cell responses measured by flow cytometry or other methods
6. Infant Participants: • RSV-RTI. • RSV-LRTI. • Severe RSV-LRTI. • RSV very severe LRTI. • RSV hospitalization.

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 9

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 25 files

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

Application history

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