Clinical trial NCT05743881: A Safety, Tolerability, and Immunogenicity Study of mRNA-1345 and mRNA-1365 in Participants Aged 5 Months to <24 Months
Official title: A Phase 1, Randomized, Observer-blind, Placebo-controlled, Age De-escalation Study of the Safety, Tolerability, and Immunogenicity of mRNA-1345 and mRNA-1365 in Participants Aged 5 Months to <24 Months
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Respiratory Syncytial Virus
Human Metapneumovirus
Keywords: mRNA-1345
mRNA-1365
RSV vaccine
hMPV vaccine
RSV/hMPV vaccine
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2023-02-24
Enrollment: 310
Sex: ALL
Minimum age (years): 5
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and immunogenicity of mRNA-1365, an mRNA vaccine targeting respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) and mRNA-1345, an mRNA vaccine targeting RSV, in participants aged 5 months to \<24 months.


Eligibility criteria: Inclusion Criteria:

* The participant is 8 months to \<24 months (Part A), 5 months to \<8 months (Part B), or 8 months to \<12 months (Part C) of age at the time of randomization (Day 1/Baseline visit), who is in good general health, in the opinion of the Investigator, based on review of medical history and screening physical examination.
* In the Investigator's opinion, the parent(s)/ legally authorized representative (LAR)(s) understand and are willing and physically able to comply with protocol-mandated follow up, including all procedures, and provide written informed consent.
* The participant is growing normally for age in the opinion of the site clinician in the months prior to enrollment.
* The participant was born at full-term (≥37 weeks gestation) with a minimum birth weight of 2.5 kilograms (kg).
* For Part C Cohort 7: participant must have received nirsevimab ≥6 months prior to Day 1 Visit.
* For Part C Cohort 8: participant was eligible at any time since birth, according to national guidelines, to receive nirsevimab prior to Day 1 Visit but did not do so.

Exclusion Criteria:

* Has a known history of symptomatic RSV (Part A: within 3 months; Part B and Part C: since birth) or hMPV infection (Part A: within 3 months; Part B: since birth) prior to administration of the first dose of investigational product (IP) or has a known close contact with anyone with laboratory-confirmed RSV (Parts A, B, and C) or hMPV infection (Parts A or B) within 14 days prior to administration of the first dose of IP.
* Is acutely ill or febrile 24 hours prior to or at the screening visit. Fever is defined as a body temperature ≥38.0°Celsius/≥100.4°Fahrenheit. Participants who meet this criterion may have visits rescheduled within the relevant study visit windows.
* Has previously been administered an investigational or approved vaccine for prevention of RSV (Parts A, B, and C) or hMPV (Parts A and B) infection or if the participant's mother received an investigational or approved vaccine for the prevention of RSV (Parts A, B, and C) or hMPV (Parts A and B) infection during pregnancy.
* Has received investigational or approved agents for prophylaxis against RSV or hMPV (for example, monoclonal antibodies) or is intending to receive these during the course of the study. For Part C (Cohort 7 only), use of nirsevimab ≥6 months before Day 1 Visit is allowed.
* Has a known hypersensitivity to a component of the vaccine or its excipients. Hypersensitivity includes, but is not limited to, anaphylaxis or immediate allergic reaction of any severity to a previous dose of an mRNA vaccine or any of its components (including polyethylene glycol or immediate allergic reaction of any severity to polysorbate).
* Has a medical condition that, according to the Investigator's judgment, may pose additional risk as a result of participation, interfere with safety assessments, or interfere with interpretation of results.

Note: Other protocol-defined inclusion/exclusion criteria apply.

Primary outcomes:
measure: Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs)
timeFrame: Up to Day 120 (7 days after each injection)
measure: Number of Participants with Unsolicited Adverse Events (AEs)
timeFrame: Up to Day 141 (28 days after each injection)
measure: Number of Participants with Medically-Attended Adverse Events (MAAEs)
timeFrame: Day 1 through Day 730
measure: Number of Participants with Adverse Event of Special Interests (AESIs), Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation
timeFrame: Day 1 through Day 730
Secondary outcomes:
measure: Number of Participants with Respiratory Tract Illness (RTI), Lower Respiratory Tract Illness (LRTI), Severe LRTI, Very Severe LRTI, and Hospitalizations Associated with RSV or hMPV
timeFrame: Day 1 through Day 730
measure: Parts A and B: Geometric Mean Titer (GMT) of Serum RSV and hMPV Neutralizing Antibodies
timeFrame: Baseline up to Month 12
measure: Part C: GMT of Serum RSV Neutralizing Antibodies
timeFrame: Baseline up to Month 12
measure: Parts A and B: Geometric Mean Concentration (GMC) of Serum RSV F- and hMPV F-Binding Antibodies
timeFrame: Baseline up to Month 12
measure: Part C: GMC of Serum RSV F-Binding Antibodies
timeFrame: Baseline up to Month 12
measure: Geometric Mean Fold-Rise (GMFR) Postbaseline/baseline Neutralizing Antibody Titers
timeFrame: Baseline up to Month 12
measure: Number of Participants with Vaccine-specific T-cell Responses Measured by Flow Cytometry
timeFrame: Baseline up to month 12
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Matrix Clinical Research
state: California
city: Los Angeles
country: United States
facility: Los Angeles Children's Hospital
state: California
city: Englewood
country: United States
facility: Velocity Clinical Research, Denver
state: Colorado
city: Washington
country: United States
facility: Meridian Clinical Research
state: District of Columbia
city: Washington
country: United States
facility: Meridian Clinical Research
state: District of Columbia
city: Jacksonville
country: United States
facility: University Of Florida Health Science Center
state: Florida
city: Orlando
country: United States
facility: Accel Research Sites - Nona Pediatric Center
state: Florida
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Lafayette
country: United States
facility: MedPharmics - Platinum - PPDS
state: Louisiana
city: Worcester
country: United States
facility: Umass Memorial Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Chan Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Southfield
country: United States
facility: Great Lakes Research Institute
state: Michigan
city: Minneapolis
country: United States
facility: Pediatric Specialty Care Discovery Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine in St. Louis
state: Missouri
city: Hastings
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Durham
country: United States
facility: Duke Vaccine and Trials Unit
state: North Carolina
city: South Euclid
country: United States
facility: Senders Pediatrics
state: Ohio
city: Providence
country: United States
facility: Velocity Clinical Research - Providence
state: Rhode Island
city: North Charleston
country: United States
facility: Palmetto Pediatrics, PA
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Vaccine Research Program
state: Tennessee
city: El Paso
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Houston
country: United States
facility: Mercury Clinical Research, Inc.
state: Texas
city: Houston
country: United States
facility: CyFair
state: Texas
city: Houston
country: United States
facility: Pediatric Associates
state: Texas
city: Plano
country: United States
facility: Village Pediatrics
state: Texas
city: Richmond
country: United States
facility: Mercury Clinical Research, Inc.
state: Texas
city: Richmond
country: United States
facility: Pediatric Center
state: Texas
city: Tomball
country: United States
facility: North Houston Internal Medicine &amp; Pediatric Clinic
state: Texas
city: Seattle
country: United States
facility: Childrens Hospital Regional Medical Center
state: Washington
city: Nedlands
country: Australia
facility: Telethon Kids Institute
state: Western Australia
city: Vancouver
country: Canada
facility: BC Children's Hospital - Vaccine Evaluation Centre - Neonatology
state: British Columbia
city: Halifax
country: Canada
facility: Dalhousie University IWK Health Centre
state: Nova Scotia
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: Montreal
country: Canada
facility: Universite de Montreal - Centre Hospitalier Universitaire (CHU) Sainte-Justine
state: Quebec
city: David
country: Panama
facility: CEVAXIN David
state: Chiriquí
city: La Chorrera
country: Panama
facility: CEVAXIN Chorrera
state: Panama Oeste
city: Ciudad de Panamá
country: Panama
facility: CEVAXIN 24 de Diciembre
city: Panama City
country: Panama
facility: CEVAXIN Avenida Mexico
city: Trzebnica
country: Poland
facility: Szpital im. Sw. Jadwigi Slaskiej w Trzebnicy
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Vistamed
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Centrum Badań Klinicznych JCI Jagiellońskie Centrum Innowacji Sp. z o.o.
state: Malopolskie
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Hillbrow
country: South Africa
facility: Shandukani Research CRS
state: Gauteng
city: Johannesburg
country: South Africa
facility: Wits Health Consortium
state: Gauteng
city: Soshanguve
country: South Africa
facility: Setshaba Research centre
state: Gauteng
city: Cape Town
country: South Africa
facility: Family Centre for Research with Ubuntu (FAMCRU)- Tygerberg
state: Western Cape
city: Cape Town
country: South Africa
facility: Practice Dr Jan Vermeulen
state: Western Cape
city: Santiago de Compostela
country: Spain
facility: Complexo Hospitalario Universitario De Santiago
state: A Coruña
city: Lleida
country: Spain
facility: Hospital Universitario Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Carlos III-Hospital Universitario La Paz
city: Liverpool
country: United Kingdom
facility: Alder Hey NHS Foundation Trust - Pharmacy Clinical Trials
city: London
country: United Kingdom
facility: St George's Hospital
city: London
country: United Kingdom
facility: Imperial College London and Imperial College Healthcare NHS
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals
city: Oxford
country: United Kingdom
facility: John Radcliffe Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: