A Phase 2, Randomized, Observer-blind, Active-control Study to Evaluate the Immunogenicity, Reactogenicity, and Safety of mRNA-1083 (Influenza and COVID-19) Vaccine in Adults ≥18 to <65 Years of Age

The purpose of this study is to evaluate the immunogenicity, reactogenicity, and safety, of mRNA-1083 multicomponent influenza and COVID-19 vaccine in adults ≥18 to <65 years of age.

Start Date07 Mar 2025

Sponsor / Collaborator

ModernaTX, Inc.

NCT06694389

/ Active, not recruitingPhase 3

A Phase 3, Randomized, Observer-Blind, Active-Control Study to Evaluate the Immunogenicity, Reactogenicity, and Safety of mRNA-1083 (SARS-CoV-2 and Influenza) Vaccine in Healthy Adults ≥50 Years of Age

The purpose of the study is to evaluate the immunogenicity, reactogenicity, and safety of mRNA-1083 in adults 50 years of age and older in participating countries (Japan, Taiwan, and South Korea).

Start Date18 Nov 2024

Sponsor / Collaborator

ModernaTX, Inc.

NCT06508320

/ Active, not recruitingPhase 2

A Phase 2, Randomized, Observer-blind Study to Evaluate the Safety, Reactogenicity, and Immunogenicity in Relation to the Product Attributes of mRNA-1083 (SARS-CoV-2 and Influenza) Vaccine in Adults ≥50 to <65 Years of Age

The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity in relation to the product attributes of mRNA-1083 vaccine when administered as a single intramuscular (IM) injection in adults ≥50 to <65 years of age.

Start Date15 Jul 2024

Sponsor / Collaborator

ModernaTX, Inc.

100 Clinical Results associated with mRNA-1083

100 Translational Medicine associated with mRNA-1083

100 Patents (Medical) associated with mRNA-1083

Literatures (Medical) associated with mRNA-1083

10 Jun 2025·JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Immunogenicity and Safety of Influenza and COVID-19 Multicomponent Vaccine in Adults ≥50 Years

Article

Author: Rudman Spergel, Amanda K. ; Urdaneta, Veronica ; Carmona, Lizbeth ; Girard, Bethany ; Miller, Jacqueline ; Mehta, Darshan ; Espinosa-Fernandez, Ivette ; Ananworanich, Jintanat ; Sinkiewicz, Melissa ; Shaw, Christine A. ; Deng, Weiping ; Callendret, Benoit ; Paila, Yamuna D. ; Johnson, Kimball ; Das, Rituparna ; Schaefers, Kristin ; Kostanyan, Lusine ; Cardona, Jose ; Wu, Iris

Importance:

Uptake of recommended seasonal influenza and COVID-19 vaccines remains suboptimal.

Objective:

To assess the immunogenicity and safety of an investigational mRNA-1083 vaccine against seasonal influenza and SARS-CoV-2 in adults 50 years and older.

Design, Setting, and Participants:

This phase 3, randomized, observer-blinded trial was conducted across 146 US sites in adults 50 years and older enrolled between October 19, 2023, and November 21, 2023. Data extraction was complete on April 9, 2024.

Interventions:

Participants in 2 age cohorts (≥65 years and 50-64 years) were randomly assigned (1:1) to receive mRNA-1083 plus placebo or coadministered licensed quadrivalent seasonal influenza (≥65 years: high-dose quadrivalent inactivated influenza vaccine [HD-IIV4]; 50-64 years: standard-dose IIV4 [SD-IIV4]) and COVID-19 (all ages: mRNA-1273) vaccines.

Main Outcomes and Measures:

The primary objectives were to demonstrate the noninferiority of humoral immune responses following mRNA-1083 vs comparators against vaccine-matched strains at day 29 and to evaluate the reactogenicity and safety of mRNA-1083. Secondary objectives included demonstration of superiority of humoral immune responses elicited by mRNA-1083 relative to comparators at day 29.

Results:

Overall, 8015 participants were enrolled and vaccinated (4017 aged ≥65 y and 3998 aged 50-64 y). Among adults 65 years and older and 50 to 64 years, the median age was 70 and 58 years, 54.2% and 58.8% were female, 18.4% and 26.7% were Black or African American, and 13.9% and 19.3% were Hispanic or Latino, respectively. Noninferior immunogenicity of mRNA-1083 was demonstrated against all vaccine-matched influenza and SARS-CoV-2 strains based on lower bound of the 97.5% CI of the geometric mean ratio greater than 0.667 and lower bound of the 97.5% CI of the seroconversion/seroresponse rate difference greater than −10%. mRNA-1083 elicited higher immune responses than SD-IIV4 (50-64 years) for all 4 influenza strains and HD-IIV4 (≥65 years) for 3 influenza strains (A/H1N1, A/H3N2, B/Victoria) and against SARS-CoV-2 (all ages). Solicited adverse reactions were numerically higher in frequency and severity after mRNA-1083 vaccination than comparators in both age cohorts (≥65 y: 83.5% and 78.1%; 50-64 y: 85.2% and 81.8%); most were grade 1 or 2 in severity and of short duration. No safety concerns were identified.

Conclusions and Relevance:

In this study, mRNA-1083 met noninferiority criteria and induced higher immune responses than recommended standard care influenza (standard and high dose) and COVID-19 vaccines against all 4 influenza strains (among those ages 50-64 y), the 3 clinically relevant influenza strains (among those aged ≥65 y), and SARS-CoV-2 (all ages), with an acceptable tolerability and safety profile.

Trial Registration:

ClinicalTrials.gov Identifier: NCT06097273

01 May 2025·NATURE MEDICINE

mRNA-based seasonal influenza and SARS-CoV-2 multicomponent vaccine in healthy adults: a phase 1/2 trial

Article

Author: Paila, Yamuna D ; Henry, Carole ; Guo, Ruiting ; Eger, Charles H ; Deng, Weiping ; Sinkiewicz, Melissa ; Ananworanich, Jintanat ; Schaefers, Kristin ; Shaw, Christine A ; Rudman Spergel, Amanda K ; Shao, Sarah ; Carmona, Lizbeth ; Kandinov, Boris

A multicomponent vaccine targeting several seasonal respiratory pathogens may provide simultaneous protection in a single-injection regimen. We present interim (28 days) findings from a phase 1/2 study of an mRNA-based multicomponent vaccine (mRNA-1083), encoding seasonal influenza and SARS-CoV-2 antigens. Adults (18-79 years) were randomly assigned to receive different compositions of mRNA-1083 at varying dose levels on day 1. The primary study objectives were reactogenicity through 7 days and safety through 28 days postvaccination, and the secondary study objective was immunogenicity against vaccine-matched influenza and SARS-CoV-2 strains at day 29 assessed by hemagglutination inhibition and pseudovirus neutralization assays, respectively. The multicomponent mRNA-1083 vaccine was generally well-tolerated, with most solicited adverse reactions being Grade 1 or 2 in severity. The incidence of unsolicited adverse events was similar across vaccine groups. mRNA-1083 induced immune responses against influenza and SARS-CoV-2 that were, in general, similar to or higher than those achieved with licensed quadrivalent influenza (standard or high dose) and SARS-CoV-2 (bivalent mRNA-1273) vaccines. These data support ongoing phase 3 evaluation of the mRNA-1083 vaccine. ClinicalTrials.gov registration: NCT05827926 .

08 Dec 2023·Emerging microbes & infections

Rational design of an influenza-COVID-19 chimeric protective vaccine with HA-stalk and S-RBD

Article

Author: Zhang, Rong ; Lu, Xuancheng ; Xu, Ke ; Wang, Xi ; Bi, Yuhai ; Liao, Pu ; Han, Pu ; Zhang, Cheng ; Gao, George F. ; Huan, Yu ; Wu, Guizhen ; Xie, Yufeng ; Li, Xiaoyan ; Liu, Sheng ; Hao, Tianjiao ; Lei, Wenwen ; Liu, Peipei ; Li, Ying ; Xu, Kun ; Zhu, Baoli ; Li, Yulei ; Lu, Yafei ; Zhao, Xin ; Jin, Xiyue ; Song, Hao

Highly contagious respiratory illnesses like influenza and COVID-19 pose serious risks to public health. A two-in-one vaccine would be ideal to avoid multiple vaccinations for these diseases. Here, we generated a chimeric receptor binding domain of the spike protein (S-RBD) and hemagglutinin (HA)-stalk-based vaccine for both SARS-CoV-2 and influenza viruses. The S-RBD from SARS-CoV-2 Delta was fused to the headless HA from H1N1 (H1Delta), creating a chimera that forms trimers in solution. The cryo-electron microscopy structure of the chimeric protein complexed with the RBD-targeting CB6 and the HA-stalk-targeting CR9114 antibodies shows that the trimeric protein is stable and accessible for neutralizing antibody binding. Immunization with the vaccine elicited high and long-lasting neutralizing antibodies and effectively protected mice against the challenges of lethal H1N1 or heterosubtypic H5N8, as well as the SARS-CoV-2 Delta or Omicron BA.2 variants. Overall, this study offers a two-in-one universal vaccine design to combat infections caused by both SARS-CoV-2 variants of concern and influenza viruses.

News (Medical) associated with mRNA-1083

11 Jun 2025

·firstwordpharma.com

Vaccine readouts from Vaxart's norovirus pill, Novavax's COVID-19/flu combo

Vaxart and Novavax reported data from their respective norovirus and COVID-19/flu combination vaccines on Wednesday. The early-stage results for Vaxart's programme pushed its stock up 28%, while Novavax's candidate will likely face higher scrutiny given US health regulators' increased standards for COVID-19 jabs (see – Physician Views Results: Doctors divided on ethics, impact of new COVID-19 policy).Last month, the FDA announced that it would require "new vaccines" to be tested in placebo-controlled trials. A regulatory framework for COVID-19 vaccines specifically detailed how booster shots could be approved for older adults and younger, at-risk individuals on the basis of immunogenicity data, but that placebo-controlled trials would be required to clear updated jabs for healthy people between the ages of five months and 65 years old. A day after the framework was released, Moderna voluntarily withdrew its marketing for mRNA-1083, a combination COVID-19/flu vaccine, after the FDA said that Phase III flu efficacy data would be required for approval (see – ViewPoints: A vaccine expert's grim verdict on Kennedy's health agenda). Pill protectionVaxart, which develops oral recombinant pill vaccines, shared Phase I data suggesting that its second-generation norovirus constructs designed to protect against the GI.1 and GII.4 genotypes can elicit a better immune response than its initial versions. The company randomised 60 patients evenly across three cohorts to receive either its first-generation products, an equivalent dose of its updated vaccine constructs, or a low-dose of the next-gen pills. Topline data showed that patients who received the standard dose had a 141% increase in GI.1 norovirus blocking antibody assay (NBAA) titres compared with the first-generation version, and a 94% increase for GII.4 NBAA titres. "Consistent with what we previously demonstrated in animal models, these clinical data prove that our second-generation constructs increased antibody titres in humans, providing additional compelling evidence of the potential of our oral pill vaccine candidates," said Sean Tucker, Vaxart’s founder and chief scientist. "The significant increases in NBAA titers reported today give us high confidence that our second-generation constructs will provide even greater protection against infection."Vaxart plans to move its norovirus vaccine pills into Phase IIb testing next half, but advancing the programme is dependent on if it can secure funding or a partner. If the company does find the means to continue work on the constructs, it said a Phase III study could launch next year. Setting up for registrational studyNovavax said that its COVID-19-Influenza Combination (CIC) vaccine induced similar immune responses as two separate jabs in a descriptive Phase III study of 2,000 adults aged 65 and older.The trial compared the CIC programme — as well as an experimental, standalone trivalent hemagglutinin nanoparticle seasonal influenza (tNIV) jab designed to protect against the H1N1, H3N2 and B flu strains — against Novavax's own COVID-19 vaccine Nuvaxovid and Sanofi's Fluzone HD. According to the company, both investigational programmes elicited "robust" immune responses to their respective viral strains, reaching a 2.4 to 5.7-fold increase compared with baseline. The study was not powered to demonstrate statistical significance, but rather to inform the design of a registrational Phase III trial. In regards to safety, both the CIC and tNIV candidates were well tolerated and had reactogenicity similar to the two comparators, with nearly all adverse events being mild or moderate.

VaccinePhase 3Clinical ResultmRNAPhase 1

31 May 2025

·firstwordpharma.com

FDA approves Moderna's next-gen COVID-19 jab, but with expected limitations

The FDA on Saturday greenlit Moderna's next-generation COVID-19 vaccine, mNEXSPIKE (mRNA-1283), but unlike its predecessor, the jab will be restricted to adults 65 and older, or those between the ages of 12 and 64 who are at high risk for severe disease. The biotech's first mRNA-based COVID-19 jab, Spikevax, was approved for individuals 12 years of age and older, regardless of risk.A spokesperson for Moderna told FirstWord that mNEXSPIKE uses a refined target to generate antibodies against the SARS-CoV-2 virus, which allows for the use of a dose that's one-fifth the size of Spikevax's — a 10-μg dose versus 50 μg.mNEXSPIKE's narrower label matches that of Novavax's protein-based COVID-19 jab Nuvaxovid, which received FDA approval earlier this month after a weeks-long delay. The limited label for older and at-risk individuals is aligned with a recent regulatory framework released by FDA Commissioner Marty Makary and newly appointed Center for Biologics Evaluation and Research Director Vinay Prasad that requires placebo-controlled testing for COVID-19 vaccines to be approved in the 12-to-64-years-old population. While mNEXSPIKE was not tested in a placebo-controlled trial, the vaccine was evaluated in a Phase III study against an active control. Compared with Moderna's Spikevax jab, mNEXSPIKE induced a stronger immune response against COVID-19, and demonstrated a 9.3% higher relative vaccine efficacy (rVE) in individuals aged 12 years and older.Virology and immunology expert Paul Offit told FirstWord that the FDA's move to require placebo-controlled trials for "new vaccines" is unethical if there is an existing vaccine with which to compare it against. For the full interview with Offit, see ViewPoints: A vaccine expert's grim verdict on Kennedy's health agenda.mNEXSPIKE's approval comes after Moderna was hit with a setback for its combo flu/COVID-19 vaccine mRNA-1083, which comprises components of mNEXSPIKE. The biotech voluntarily withdrew an application with the FDA seeking approval of the combination product earlier this month after the agency said that it required Phase III flu efficacy data.The vaccine developer also had its contract with the Department of Health and Human Services (HHS) to develop vaccines for pre-pandemic influenzas, including bird flu, canceled this week. Moderna had received a $590-million award from HHS, as well as $176 million from the department's Biomedical Advanced Research and Development Authority (BARDA).

VaccinePhase 3Drug ApprovalClinical ResultmRNA

29 May 2025

·firstwordpharma.com

Moderna reports early immunogenicity data for bird flu jab as HHS pulls funding

Moderna is facing another setback from the vaccine-sceptical Trump administration, with the company disclosing Wednesday that the Department of Health and Human Services (HHS) has canceled over $760 million in funding to develop vaccines for pre-pandemic influenzas — including the bird flu. The announcement came in conjunction with an interim data readout from Moderna's 300-person Phase I/II trial of its H5 avian influenza vaccine, mRNA-1018. More than 97% of participants who received two doses of the experimental vaccine had hemagglutination inhibition (HAI) antibody titers ≥1:40 — the level considered to be protective — at three weeks after the second vaccination. About 2% of individuals had protective levels of HAI antibodies at baseline. In addition, mRNA-1018 was generally well-tolerated, with most adverse reactions being either Grade 1 or 2, and no dose-limiting tolerability concerns. Moderna plans to present additional data at an upcoming scientific meeting. "While the termination of funding from HHS adds uncertainty, we are pleased by the robust immune response and safety profile observed," CEO Stéphane Bancel said in a company release. "These clinical data in pandemic influenza underscore the critical role mRNA technology has played as a countermeasure to emerging health threats."Moderna had been counting on a $590-million contract — awarded in the final days of the Biden administration — to fund late-stage development of mRNA-1018. The biotech had also received a $176-million award from HHS's Biomedical Advanced Research and Development Authority (BARDA) last year to develop mRNA-based vaccines to head off future viral outbreaks.Without the funding, Moderna said it will "explore alternatives for late-stage development and manufacturing of the H5 programme."There had been hints earlier this year that Moderna's influenza award was in danger of being pulled. In February, an HHS spokesperson said that "four years of the Biden administration’s failed oversight have made it necessary to review agreements for vaccine production."The canceled contract is the latest fallout from the US's overhaul of how it regulates and develops vaccines, overseen by HHS Secretary Robert F. Kennedy Jr. For more, see Vital Signs: Moderna starts sweating vaccine climate at the 'new FDA'.Last week, Moderna voluntarily withdrew an application seeking approval of its combination influenza/COVID-19 vaccine mRNA-1083 for adults aged 50 years and older after the FDA said that Phase III flu efficacy data would be required.HHS agencies have released a flurry of vaccine policy changes this month. The FDA will now require placebo-controlled trials for "new vaccines," including COVID-19 boosters for healthy individuals under the age of 65.Earlier this week, Kennedy announced that the Centers for Disease Control and Prevention (CDC) would no longer recommend healthy children and pregnant women receive COVID-19 vaccines.However, Kennedy's influence on US health policy has drawn criticism, with virology and immunology expert Paul Offit warning in a recent FirstWord interview that the secretary's health agenda may be based more on ideology than evidence (see – ViewPoints: A vaccine expert's grim verdict on Kennedy's health agenda).

VaccinemRNAPhase 3

100 Deals associated with mRNA-1083

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
COVID-19	Canada	Moderna, Inc.	01 Feb 2025

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Influenza, Human	Phase 3	United States	Moderna, Inc.	26 Oct 2023
SARS-CoV-2 acute respiratory disease	Phase 2	United States	ModernaTX, Inc.	15 Jul 2024
SARS-CoV-2 acute respiratory disease	Phase 2	Canada	ModernaTX, Inc.	15 Jul 2024
Severe Acute Respiratory Syndrome	Phase 2	United States	ModernaTX, Inc.	14 Apr 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06097273 (CTgov)	Phase 3	COVID-19 \| Influenza, Human	8,061	Placebo+mRNA-1083 (Cohort A1: mRNA-1083 and Placebo)	zqgzvgkkal(gqjqnqjhxg) = nmluafcary kftsvbsdzs (hmzglqlhey, xtnbkqqxye - cxfkyzfbnn) View more	-	13 Jun 2025
				Influenza Vaccine (Cohort A2: Influenza Vaccine and COVID-19 Vaccine)	zqgzvgkkal(gqjqnqjhxg) = utgzvrmcxv kftsvbsdzs (hmzglqlhey, utvidrrxjn - gcgwwypzlg) View more
NCT06097273 (Pubmed) Manual	Phase 3	COVID-19 \| Influenza, Human	8,015	mRNA-1083+placebo (aged ≥65)	xzrjawylyr(qmwojdaxhs) = xotuinxoub mnyvdnrabp (envgoeljyu )	Positive	07 May 2025
				mRNA-1083+HD-IIV4 (aged ≥65)	xzrjawylyr(qmwojdaxhs) = xfphfthfzl mnyvdnrabp (envgoeljyu )
NCT06097273 (Corporate Publications) Manual	Phase 3	COVID-19 \| Influenza, Human	8,075	mRNA-1083	ytfntpuzwv(adilzqovbk) = from a single dose of mRNA-1083 were found to be non-inferior versus the co-administered, routinely recommended, licensed comparators. In both age cohorts, mRNA-1083 also elicited statistically significantly higher immune responses against three influenza virus strains (H1N1, H3N2, and B/Victoria) and against SARS-CoV-2. mpocghylcs (mhwreijxof ) Met View more	Positive	10 Jun 2024
				Fluarix
NCT05827926 (NEWS) Manual	Phase 1/2	COVID-19	-	mRNA-1083	kpjmrbwhwq(ityabemtsv): GMT ratios = ≥1.0 View more	Positive	04 Oct 2023
				Fluarix

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

AI Agents Built for Biopharma Breakthroughs

Accelerate discovery. Empower decisions. Transform outcomes.

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

mRNA-1083

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation