A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in Pregnant Women, and Safety and Immunogenicity in Infants Born to Vaccinated Mothers

The purpose of the study is to evaluate the reactogenicity, safety, and immunogenicity of an investigational respiratory syncytial virus (RSV) vaccine, mRNA-1345, in pregnant women, and safety and immunogenicity in infants born to vaccinated mothers.

Start Date15 Nov 2023

Sponsor / Collaborator

ModernaTX, Inc.

NCT06097299 / Active, not recruitingPhase 2

A Phase 2, Randomized, Observer-blind Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in Children 2 to <18 Years of Age at High Risk of Respiratory Syncytial Virus Disease

Part A: The purpose is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1345 in children aged 2 to <5 years (Cohort 1) and in children at high risk of respiratory syncytial virus (RSV) disease 5 to <18 years of age (Cohort 2) to inform the dose level selection for the next phase of development (Phase 3).
Part B: The purpose is to provide surveillance for RSV disease for the next RSV season (6 months after re-enrollment) and safety follow-up for Cohort 1 participants that were enrolled and dosed in Part A.

Start Date24 Oct 2023

Sponsor / Collaborator

ModernaTX, Inc.

NCT06067230 / Active, not recruitingPhase 3

A Phase 3 Study to Evaluate the Immunogenicity and Safety of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in High-Risk Adults

The study is divided into 2 parts (Part A and Part B). Part A of the study will evaluate the safety and immune response to mRNA-1345 in high-risk adults aged ≥18 to <60 years.
Part B of the study will evaluate the safety and immune response to mRNA-1345 in adults who received solid organ transplant (SOT).

Start Date06 Oct 2023

Sponsor / Collaborator

ModernaTX, Inc.

100 Clinical Results associated with Respiratory Syncytial Virus Vaccine(Moderna)

100 Translational Medicine associated with Respiratory Syncytial Virus Vaccine(Moderna)

100 Patents (Medical) associated with Respiratory Syncytial Virus Vaccine(Moderna)

Literatures (Medical) associated with Respiratory Syncytial Virus Vaccine(Moderna)

15 Nov 2024·JOURNAL OF INFECTIOUS DISEASES

Humoral Immunogenicity of mRNA-1345 RSV Vaccine in Older Adults

Article

Author: Doreski, Pablo A ; Pérez–Breva, Lina ; Perez Marc, Gonzalo ; Slobod, Karen ; Huang, Wenmei ; Rämet, Mika ; Lan, Lan ; Jimenez, Gilberto ; Lin, Nina ; Priddy, Frances ; Duncan, Christopher J A ; Le Cam, Nancy ; Das, Rituparna ; Shaw, Christine A ; Ahmed, Salahuddin ; Tomassini, Joanne E ; Miller, Jacqueline M ; Goswami, Jaya ; Stoszek, Sonia K ; Ujiie, Mugen ; Du, Jiejun ; Baqui, Abdullah H ; Zaman, Khalequz ; Wilson, Eleanor ; Zhou, Honghong ; Mehta, Shraddah ; Kapoor, Archana

Abstract:

Background:

The mRNA-1345 vaccine demonstrated efficacy against respiratory syncytial virus (RSV) disease with acceptable safety in adults aged ≥60 years in the ConquerRSV trial. Here, humoral immunogenicity results from the trial are presented.

Methods:

This phase 2/3 trial randomly assigned adults (≥60 years) to mRNA-1345 50-µg encoding prefusion F (preF) glycoprotein (n = 17 793) vaccine or placebo (n = 17 748). RSV-A and RSV-B neutralizing antibody (nAb) and preF binding antibody (bAb) levels at baseline and day 29 postvaccination were assessed in a per-protocol immunogenicity subset (PPIS; mRNA-1345, n = 1515; placebo, n = 333).

Results:

Day 29 nAb geometric mean titers (GMTs) increased 8.4-fold against RSV-A and 5.1-fold against RSV-B from baseline. Seroresponses (4-fold rise from baseline) in the mRNA-1345 groups were 74.2% and 56.5% for RSV-A and RSV-B, respectively. Baseline GMTs were lower among participants who met the seroresponse criteria than those who did not. mRNA-1345 induced preF bAbs at day 29, with a pattern similar to nAbs. Day 29 antibody responses across demographic and risk subgroups were generally consistent with the overall PPIS.

Conclusions:

mRNA-1345 enhanced RSV-A and RSV-B nAbs and preF bAbs in adults (≥60 years) across various subgroups, including those at risk for severe disease, consistent with its demonstrated efficacy in the prevention of RSV disease.

Clinical Trials Registration:

NCT05127434.

01 Nov 2024·Respiratory Investigation

Safety and immunogenicity of an mRNA-based RSV vaccine in Japanese older adults aged ≥60 years: A phase 1, randomized, observer-blind, placebo-controlled trial

Article

Author: Chen, Grace L. ; Guo, Ruiting ; Simorellis, Alana K. ; Stoszek, Sonia K ; Panozzo, Catherine A. ; Fitz-Patrick, David ; Mithani, Runa ; Goswami, Jaya ; Kapoor, Archana ; Wilson, Eleanor ; Shaw, Christine A. ; Chen, Grace L ; Wilson, Lauren ; Reuter, Caroline ; Mills, Anthony ; Shaw, Christine A ; Dhar, Rakesh ; Panozzo, Catherine A ; Stoszek, Sonia K. ; Mihara, Hanako ; Simorellis, Alana K

BACKGROUND:

Respiratory syncytial virus (RSV) represents a global health concern, including in older adults. This study assessed the safety and immunogenicity of mRNA-1345, an investigational mRNA RSV vaccine, in adults aged ≥60 years of Japanese descent.

METHODS:

In this phase 1, randomized, observer-blind, placebo-controlled study, participants were randomized to receive one injection of mRNA-1345 100 μg or placebo. Solicited local and systemic adverse reactions (ARs) were collected within 7 days following injection. Unsolicited adverse events (AEs) were collected up to 28 days after injection; AEs of special interest, medically attended AEs, and serious AEs were collected through end of study. Immunogenicity was assessed at baseline and months 1, 2, 3, and 6 following injection.

RESULTS:

Twenty-five adults of Japanese descent aged ≥60 years received one injection of mRNA-1345 100 μg (n = 21) or placebo (n = 4). mRNA-1345 was well-tolerated; the most common local and systemic solicited ARs were injection site pain, and fatigue and myalgia, respectively, which were generally mild to moderate and transient. No serious AEs were reported. Neutralizing (nAb) and binding (bAb) antibodies were detectable at baseline, consistent with prior RSV exposure. mRNA-1345 boosted RSV nAb titers and preF bAb concentrations 1 month post-injection (geometric mean fold rise: RSV-A nAb, 11.2; RSV-B nAb, 6.6; preF bAb, 9.1). Titers among mRNA-1345 recipients remained above baseline through 6 months.

CONCLUSIONS:

mRNA-1345 100 μg was well-tolerated among older adults of Japanese descent and induced nAbs and bAbs which were durable through 6 months, supporting its continued development.

TRIAL REGISTRATION:

ClinicalTrials.gov, NCT04528719.

14 Dec 2023·The New England journal of medicineQ1 · MEDICINE

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults

Q1 · MEDICINE

Article

Author: Slobod, Karen ; Doreski, Pablo A ; Wilson, Eleanor ; Monroy, Jorge ; Stoszek, Sonia K ; Kuter, Barbara J ; Rämet, Mika ; Lan, Lan ; Reuter, Caroline ; Duncan, Christopher J A ; Chen, Grace L ; Dhar, Rakesh ; Simorellis, Alana K ; Walsh, Edward E ; Mithani, Runa ; Goswami, Jaya ; Wilson, Lauren ; Ghaswalla, Parinaz ; Baqui, Abdullah H ; Ujiie, Mugen ; Huang, Wenmei ; Du, Jiejun ; Perez-Marc, Gonzalo ; Mehta, Shraddha ; Schödel, Florian ; Kapoor, Archana ; Das, Rituparna ; Shaw, Christine A ; Falsey, Ann R ; Pérez-Breva, Lina ; Miller, Jacqueline M ; Panozzo, Catherine A ; Zaman, Khalequ

BACKGROUND:

Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation.

METHODS:

In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 μg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed.

RESULTS:

Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group.

CONCLUSIONS:

A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

News (Medical) associated with Respiratory Syncytial Virus Vaccine(Moderna)

13 Dec 2024

·www.biopharmadive.com

FDA panel seeks more data on RSV vaccine safety in infants

A panel of experts convened by the Food and Drug Administration called for more data to be collected on the safety of vaccines for respiratory syncytial virus in infants, indicating caution after the agency partially paused enrollment of clinical trials testing certain RSV shots in young children.The advisory committee, which met at the FDAs request Thursday, did not reach a conclusion about the cause of a safety signal observed in pediatric testing of Modernas RSV vaccine. Panel members were largely in agreement on needing additional information before moving forward. The committee did not vote on any specific safety precautions, or on whether trials currently on hold can move forward.Investigators in a Moderna trial reported cases of severe RSV in infants between 5 months to 8 months old who had received one of two formulations of the companys vaccine. The study was paused in July, and the FDA eventually put a hold on enrolling children under the age of two into all clinical studies testing RSV vaccine candidates that arent of the live-attenuated type. The hold also applies to children aged 2 years to 5 years who have never been infected with RSV.According to briefing documents prepared by FDA staff, there are 26 candidates in pediatric clinical development, 11 of which use other technology than live-attenuated.We are confronted by a very complicated situation, said Arnold Monto, a panelist and professor emeritus of epidemiology and public health at the University of Michigans School of Public Health.Modernas vaccines are built from messenger RNA. It sells one formulation of its RSV shot for older adults under the brand name mResvia, and is testing that and another thats designed to also protect against human metapneumovirus in children.The company first tested its RSV vaccines in children between 8 months and 24 months old before enrolling infants between 5 months and 7 months of age. Among that latter group, five cases of severe RSV were reported among participants who received Modernas shot, versus one case in those given placebo. There was also one case of an RSV-associated hospitalization in an older child participant that occurred after Moderna proceeded with testing in young infants.While concerned about the cases reported, advisers noted the trials safeguards did hold.What is already in place is working, said Adam Berger, director of clinical and healthcare research policy in the Office of Science Policy at the National Institutes of Health. We just don't really have a good understanding of the mechanism that is driving the safety signal.Beger noted that, of the 11 pediatric trials on partial hold, data was only available from Moderna. I don't think we can make a generalized answer to a technology based on just having one study, I fully agree there is an absolute safety signal here, and the steps that we're taking are I would support, but I'm not sure I can actually apply that to all mRNA programs, he said.Some advisers also noted that many of the enrolled infants in Modernas study were located in Panama, and it was unclear if any local factors affected the immune response of individuals, said Michael Nelson, professor of medicine and division chief for asthma, allergy, and immunology at University of Virginia Health.The committee emphasized the need gaining better understanding of the immune response in different age groups, and called for continued monitoring of immune responses in trial participants. They indicated interest in further discussions as that data comes in. None called for ending all studies testing RSV candidates in infants.Advisers also spoke positively about Sanofis monoclonal antibody Beyfortus, which is approved to provide temporary protection from RSV in infants, as well as use of Pfizers RSV vaccine as a maternal immunization to pass passive protection along to newborns. '

VaccineClinical StudyImmunotherapymRNA

10 Dec 2024

·endpts.com

Cases of severe RSV in two Moderna vaccine candidates' trials raise questions about future

Ahead of an advisory committee meeting later this week, the FDA revealed that all studies for RSV vaccines in young children and infants are currently on hold, including two not previously disclosed by Moderna. The FDA said Tuesday that it observed “an imbalance in severe/very severe cases of RSV” lower respiratory tract infections (LRTI) in both of Moderna’s candidates, known as mRNA-1345 and mRNA-1365, the former of which was discontinued in September for infants. Moderna’s trials evaluated infants between the ages of 5 months and 8 months, receiving 15 µg of either vaccine. In one cohort of the study evaluating both vaccine candidates, of the 20 infants who received mRNA-1365, 10 infants later had symptomatic RSV, and three of those cases were severe or very severe, according to the FDA. However, in the placebo group, 12 of the 20 infants later caught RSV and one had a severe or very severe case. The agency said the data have “uncertain implications for the ongoing and future pediatric development of other non-live attenuated RSV vaccines.” Moderna’s stock $MRNA was down about 5% on Tuesday morning. The company, which received FDA approval in May for mRNA-1345, now called mResvia, for older adults, did not immediately respond to a request for comment. While the committee will not vote during Thursday’s advisory committee meeting, the FDA is asking the outside experts to discuss whether the currently available evidence around RSV vaccines “indicates a potential safety concern more broadly applicable to the evaluation of RSV vaccine candidates in infants and toddlers.” All studies of RSV vaccine candidates in the US for children younger than 2 years old and RSV-naïve children ages 2 through 5 years old are currently on clinical hold, according to the FDA’s briefing document . Back in September, Moderna said it had halted its development of mRNA-1345 at its annual R&D day. According to the briefing document, the company was made aware of the severe LRTI with a positive RSV test in two or more study participants on July 17. Two days later, Moderna notified the FDA of a study-wide pause, and the regulator put a clinical hold on the program. Moderna did not publicly disclose the clinical hold, and on Sept. 12, it listed the RSV program for seronegative children younger than 2 years old under discontinued programs, saying then that “the company does not expect [the] program to advance beyond the ongoing Phase 1 based on emerging clinical data.” The questions posed by the FDA ahead of Thursday’s meeting also have a complicated history, and the agency is reminding its experts that early efforts to develop RSV vaccines more than 50 years ago unexpectedly worsened the disease in some infants. In the 1960s, pediatric RSV vaccine development was stalled due to vaccine-associated enhanced respiratory disease (VAERD) that led to two toddler deaths. At that time, the companies were developing formalin-inactivated respiratory syncytial virus (FI-RSV) vaccines, according to the FDA, which noted the similarities they’re seeing with Moderna’s data. In light of the available data from mRNA-1345 and mRNA-1365, the FDA said a decision to re-initiate enrollment of at-risk populations for VAERD and allow future pediatric studies of other non-live attenuated RSV vaccines will need to consider seven items. This includes whether and what data may be helpful to stratify potential trial risks based on vaccine technology and/or antigenic composition and how potential RSV monoclonal antibody and RSV vaccine interactions should be addressed in clinical trial designs.

VaccinemRNAClinical StudyDrug Approval

11 Nov 2024

·www.pharmaceutical-technology.com

Moderna’s mRESVIA vaccine gains Health Canada approval

The approval marks the introduction of the first mRNA RSV vaccine in Canada. Credit: MargJohnsonVA via Shutterstock. Moderna has received Health Canada’s approval for its respiratory syncytial virus messenger ribonucleic acid (mRNA) vaccine mRESVIA, designed to prevent lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals aged 60 and over. This marks the introduction of the first mRNA RSV vaccine in Canada and the second approved product of Moderna in the country. The approval by Health Canada is supported by the outcomes from the ConquerRSV Phase III study, which involved approximately 37,000 patients aged 60 and above across 22 countries. The trial’s primary analysis indicated an 83.7% efficacy in preventing RSV LRTD after a median follow-up of 3.7 months. Moderna CEO Stéphane Bancel said: “Today’s approval is an example of how our mRNA platform can help address significant public health challenges like RSV. “As our second product approved by Health Canada, mRESVIA underscores our commitment to leveraging mRNA technology to protect vulnerable populations and contribute to a healthier future for Canadians.” mRESVIA is reportedly currently the only vaccine available in a distinct single-dose prefilled syringe format. This is intended to streamline the vaccination process for healthcare professionals, potentially reducing the risk of errors and saving time. The expected availability of mRESVIA in Canada is in early 2025. The company is also actively seeking marketing authorisations in various jurisdictions globally. Canada is the fourth to grant approval, following Europe, Qatar, and the US. Canada’s National Advisory Committee on Immunization endorses RSV vaccination for those aged 75 and over and for individuals aged 60 years and above living in chronic care facilities and nursing homes. Vaccination for community-dwelling individuals over 60 is advised to be a personal decision made after consulting with a healthcare provider. The vaccine comprises an mRNA sequence that encodes the RSV F glycoprotein, which is essential for the virus’ ability to infect host cells. The drug also received US Food and Drug Administration approval in June this year and is anticipated to be available in the country in time for the 2024-25 respiratory virus season. mRNA vaccine coverage on Pharmaceutical Technology (or Clinical Trials Arena) is supported by Trilink . Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Enhance your mRNA production with market leading capping Optimising mRNA production raises myriad questions for biomanufactures around how to navigate costs and maximise efficiency. TriLink BioTechnologies has leveraged its expertise to provide answers. Their CleanCap® M6 analog improves mRNA yields and boosts protein expression. With its newly optimised pulse-feed protocol, manufacturers can double production at just a fraction of the cost. As a proven solution in scalable IVT reactions, CleanCap® M6 ensures consistent quality and reduced costs for mRNA production. Download now to learn more. Thank you. You will receive an email shortly. Please check your inbox to download the Whitepaper. By Trilink Thematic By downloading this Whitepaper, you acknowledge that GlobalData may share your information with Trilink Thematic and that your personal data will be used as described in their Privacy Policy

Phase 3Drug ApprovalVaccineClinical ResultmRNA

100 Deals associated with Respiratory Syncytial Virus Vaccine(Moderna)

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Indication	Country/Location	Organization	Date
Respiratory Syncytial Virus Infections	EU	Moderna, Inc.	23 Aug 2024
Respiratory Syncytial Virus Infections	IS	Moderna, Inc.	23 Aug 2024
Respiratory Syncytial Virus Infections	LI	Moderna, Inc.	23 Aug 2024
Respiratory Syncytial Virus Infections	NO	Moderna, Inc.	23 Aug 2024
Pneumonia due to respiratory syncytial virus	EU	Moderna Biotech Spain, S.L.	22 Aug 2024
Pneumonia due to respiratory syncytial virus	IS	Moderna Biotech Spain, S.L.	22 Aug 2024
Pneumonia due to respiratory syncytial virus	LI	Moderna Biotech Spain, S.L.	22 Aug 2024
Pneumonia due to respiratory syncytial virus	NO	Moderna Biotech Spain, S.L.	22 Aug 2024

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Influenza, Human	Phase 3	US	ModernaTX, Inc.	01 Apr 2022
Severe Acute Respiratory Syndrome	Phase 3	US	ModernaTX, Inc.	01 Apr 2022
Human Metapneumovirus Infection	Phase 1	US	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	AU	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	CA	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	PA	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	PL	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	ZA	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	ES	ModernaTX, Inc.	15 Feb 2023
Human Metapneumovirus Infection	Phase 1	GB	ModernaTX, Inc.	15 Feb 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05127434 (Pubmed 1 \| Pubmed 2 \| N Engl J Med) Manual	Phase 2/3	Respiratory Syncytial Virus Infections	35,541	mRNA-1345	yxuznefayy(xgensnovjo) = tdoaqcoefy mkjkaqmbib (sgtedoycwn, 66.0 - 92.2) View more	Positive	14 Dec 2023
				Placebo	tmwcaugchs(lpkdwspyri) = opnnnxigyf aruxgtpwzj (unmtuudoxt )
ConquerRSV (Biospace) Manual	Phase 3	Respiratory Syncytial Virus Infections	37,000	mRNA-1345	nrewiheidq(mgfkidsgif) = wrdvxmuxir ufefrryhwp (hbqbogkmet, 66.1 - 92.2) View more	Positive	03 Aug 2023
NCT05127434 (Accesswire) Manual	Phase 3	Respiratory Syncytial Virus Infections	37,000	mRNA-1345	mwgbkpcbwx(bmynuokkhc) = dbzougyuwt xkxaagcmfc (mkqdejvzqj ) Met View more	Positive	17 Jan 2023
				Placebo	mwgbkpcbwx(bmynuokkhc) = jqkiocevax xkxaagcmfc (mkqdejvzqj ) Met View more

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