mRNA-1647 Vaccine for Cytomegalovirus Infection
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: ModernaTX, Inc.
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial tests a new vaccine called mRNA-1647 to help patients who have had a bone marrow transplant avoid CMV infections. The vaccine works by teaching the immune system to recognize and fight the virus.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.
What data supports the effectiveness of the mRNA-1647 vaccine for Cytomegalovirus infection?
The success of mRNA vaccines against COVID-19 and their promising results in cancer treatment suggest that mRNA technology can effectively stimulate the immune system. This indicates potential for the mRNA-1647 vaccine to be effective against Cytomegalovirus by using similar mechanisms to boost immune responses.
12345Is the mRNA-1647 CMV vaccine safe for humans?
The mRNA-1647 CMV vaccine has been tested in clinical trials, and no serious safety concerns have been reported. Participants experienced mild reactions, such as pain at the injection site, similar to those who received a placebo.
678910What makes the mRNA-1647 CMV vaccine treatment unique?
The mRNA-1647 CMV vaccine is unique because it uses lipid nanoparticles to deliver modified mRNA encoding CMV glycoproteins, which helps the body produce a strong immune response with both antibodies and T cells. This approach is different from traditional vaccines and aims to provide protection against CMV infection in various populations, including pregnant women and transplant patients.
67101112Eligibility Criteria
This trial is for adults who've had a bone marrow transplant, are at high risk for CMV infection, and have working major organs. They must not be pregnant or breastfeeding, agree to use contraception, and can't have HIV or recent treatments that weaken the immune system.Participant Groups
The study tests mRNA-1647 vaccine's effectiveness in preventing significant CMV infections after stopping standard anti-CMV drugs post-transplant. Participants will either receive the vaccine or a placebo to compare results.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: mRNA-1647Experimental Treatment1 Intervention
Participants will receive mRNA-1647 by intramuscular (IM) injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.
Group II: PlaceboPlacebo Group1 Intervention
Participants will receive mRNA-1647 matching placebo by IM injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Dana-Farber Cancer InstituteBoston, MA
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Who is running the clinical trial?
ModernaTX, Inc.Lead Sponsor
References
Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. [2020]Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine-complexed mRNA. Such two-component mRNA vaccines support both antigen expression and immune stimulation. These self-adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune response, comprising antigen specific CD4+ T cells, CD8+ T cells and B cells. The balanced immune response results in a strong anti-tumor effect and complete protection against antigen positive tumor cells. This tumor inhibition elicited by mRNA vaccines is a result of the concerted action of different players. After just two intradermal vaccinations, we observe multiple changes at the tumor site, including the up-regulation of many genes connected to T and natural killer cell activation, as well as genes responsible for improved infiltration of immune cells into the tumor via chemotaxis. The two-component mRNA vaccines induce a very fast and boostable immune response. Therefore, the vaccination schedules can be adjusted to suit the clinical situation. Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited. The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans.
Regulatory perspective for quality evaluation of lipid nanoparticle-based mRNA vaccines in China. [2023]In recent years, urgent unmet medical needs due to the COVID-19 pandemic have accelerated the application of mRNA technology in vaccine development, leading to some of the first approvals of mRNA vaccines in human history by regulatory agencies around the world. For market authorization, comprehensive chemistry, manufacturing and control (CMC) information is required to assure the safety and quality consistency of mRNA vaccines. Evaluating mRNA vaccines for new virus variants poses a challenge for regulators, given the rapid optimization and development based on prior platform knowledge to accelerate the development process, which is traditionally limited for biological products. Here we summarize the current regulatory considerations of CMC evaluation on mRNA vaccines based on the scientific knowledge available, which will be updated with the advance of mRNA biology and pharmaceutical science.
Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. [2023]Synthetic mRNA and the expression of therapeutic proteins have accelerated vaccine development to prevent infection and heralds a new era in targeted immunotherapy in oncology. Therapeutic mRNA vaccines rely on available tumor tissue for gene sequencing analysis to compare the patient's normal cellular DNA sequences and those of the tumor. Carrier-based mRNA vaccines for cancer immunotherapy are now in development that use delivery systems based on peptides, lipids, polymers, and cationic nano-emulsions. There have also been recent developments in dendritic cell-based mRNA vaccines. For patients with available tumor tissue samples, it is possible to develop mRNA vaccines that result in the expression of tumor antigens by antigen-presenting cells (APCs), resulting in innate and adaptive immune responses. Ongoing developments in mRNA immunotherapy include modifications in the route of administration and combined delivery of multiple mRNA vaccines with checkpoint inhibitors. This Editorial aims to present a brief overview of how mRNA immunotherapy may change the therapeutic landscape of personalized medicine for patients with solid malignant tumors.
Amplifying mRNA vaccines: potential versatile magicians for oncotherapy. [2023]Cancer vaccines drive the activation and proliferation of tumor-reactive immune cells, thereby eliciting tumor-specific immunity that kills tumor cells. Accordingly, they possess immense potential in cancer treatment. However, such vaccines are also faced with challenges related to their design and considerable differences among individual tumors. The success of messenger RNA (mRNA) vaccines against coronavirus disease 2019 has prompted the application of mRNA vaccine technology platforms to the field of oncotherapy. These platforms include linear, circular, and amplifying mRNA vaccines. In particular, amplifying mRNA vaccines are characterized by high-level and prolonged antigen gene expression at low doses. They can also stimulate specific cellular immunity, making them highly promising in cancer vaccine research. In this review, we summarize the research progress in amplifying mRNA vaccines and provide an outlook of their prospects and future directions in oncotherapy.
mRNA vaccine in cancer therapy: Current advance and future outlook. [2023]Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisition. In this review, we elaborated on the development of cancer vaccines and mRNA cancer vaccines, as well as the potential biological mechanisms of mRNA cancer vaccines and the latest progress in various tumour treatments, and discussed the challenges and future directions for the field.
Cytomegalovirus vaccines under clinical development. [2022]Congenital cytomegalovirus (CMV) infection is the most common infectious cause of disability in newborn infants. CMV also causes serious disease in solid organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. In otherwise healthy children and adults, primary CMV infection rarely causes illness. However, even asymptomatic CMV infections may predispose an individual towards an increased risk of atherosclerosis, cancer and immune senescence over the life course, although such associations remain controversial. Thus, although a vaccine against congenital CMV infection would have the greatest public health impact and cost-effectiveness, arguably all populations could benefit from an effective immunisation against this virus. Currently there are no licensed CMV vaccines, but there is increased interest in developing and testing potential candidates, driven by the demonstration that a recombinant CMV glycoprotein B (gB) vaccine has some efficacy in prevention of infection in young women and adolescents, and in CMV-seronegative SOT recipients. In this review, the recent and current status of candidate CMV vaccines is discussed. Evolving concepts about proposed correlates of protective immunity in different target populations for CMV vaccination, and how these differences impact current clinical trials, are also reviewed.
A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant. [2008]A phase I randomized, double-blind, placebo-controlled trial was done with a cytomegalovirus (CMV) vaccine based on the envelope glycoprotein, gB, combined with a novel adjuvant, MF59. Participants received CMV gB vaccine with MF59 or CMV gB with alum or placebo at 0, 1, and 6 months. A fourth vaccine was given at 12 months to a subgroup. Levels of neutralizing antibody and antibody to gB 2 weeks after the third dose of vaccine exceeded those in seropositive control subjects. the formulation with MF59 was more immunogenic than that with alum. The optimal dose of gB appeared to be between 5 and 30 microg. The fourth dose produced a prompt rise in antibody level. There were no serious adverse events associated with vaccine. Local and systemic reactions were generally mild and, except for pain at the injection site, occurred with similar frequency in recipients of placebo and CMV vaccine.
Cytomegalovirus vaccine: phase II clinical trial results. [2022]Cytomegalovirus (CMV) is one of the most significant viral pathogens during pregnancy and in immunocompromised patients. Antiviral prophylactic strategies are limited by toxicities, drug-drug interactions and development of antiviral resistance. A safe and protective vaccine against CMV is highly desirable in view of the potential positive impact on CMV-associated morbidity and mortality as well as healthcare costs. Unfortunately, this demand could not be met in the past four decades although development of a CMV vaccine has been ranked at the highest priority by the US Institute of Medicine. Multiple different vaccine candidates have been developed and evaluated in phase I clinical trials and few succeeded to phase II trials. Nevertheless, two different vaccines showed recently promising results in trials that studied healthy adults and immunocompromised solid-organ and bone-marrow transplant recipients, respectively. The gB/MF59 vaccine exhibited a vaccine efficacy of 50% in healthy, postpartum females. In transplant patients, gB/MF59 and the DNA vaccine TransVax both limited the periods of viraemia and consequently the need for antiviral treatment. The success of these trials is encouraging and will probably give new impetus to the development of an effective CMV vaccine. Sterilizing immunity may not be attainable in the near future and may not be necessary for a CMV vaccine to have a significant impact on health care as discussed in the present review.
Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. [2020]A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults.
Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. [2018]A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers. Since the protective correlates in pregnant women and transplant recipients may differ, we developed an additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65. Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T cell responses in mice. Our data demonstrate that mRNA/LNP is a versatile platform that enables the development of vaccination strategies that could prevent CMV infection and consequent disease in different target populations.
Vaccines for cytomegalovirus. [2019]Cytomegalovirus (CMV) is a leading cause of congenital infection worldwide and therefore is recognized as an important target for vaccine development. Data from natural infections and work done with animal models, including models of congenital infection, provide the rationale for their development. CMV vaccine evaluations were begun in the mid-1970's with an attenuated live virus vaccine, Towne, but this vaccine has not consistently provided protection. Most recently, data from a trial with a subunit glycoprotein B (gB) vaccine administered with the adjuvant MF59 became available. This trial, conducted in post-partum women, demonstrated that the vaccine decreased CMV infections, increasing optimism that a protective CMV vaccine could be developed. Other approaches for CMV that have entered clinical trials include replicons, DNA vaccines, prime boost strategies, and chimeric live viruses. The replicon vaccine included gB and the T cell targets phosphoprotein (pp)65 and Immediate Early (IE)1 while the DNA vaccine was given with a new adjuvant and included gB and pp65. The optimal composition for a CMV vaccine remains to be defined but trials continue with the gB vaccine and others.
A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. [2022]A therapeutic CMV vaccine incorporating an antigenic repertoire capable of eliciting a cellular immune response has yet to be successfully implemented for patients who already have acquired an infection. To address this problem, we have developed a vaccine candidate derived from modified vaccinia Ankara (MVA) that expresses three immunodominant antigens (pp65, IE1, IE2) from CMV. The novelty of this vaccine is the fusion of two adjacent exons from the immediate-early region of CMV, their successful expression in MVA, and robust immunogenicity in both primary and memory response models. Evaluation of the immunogenicity of the viral vaccine in mouse models shows that it can stimulate primary immunity against all three antigens in both the CD4(+) and CD8(+) T cell subsets. Evaluation of human PBMC from healthy CMV-positive donors or patients within 6 months of receiving hematopoietic cell transplant shows robust stimulation of existing CMV-specific CD4(+) and CD8(+) T cell subsets.