DCVC H1 HA mRNA Vaccine for Flu

Recruiting at 1 trial location

Overseen By Patricia L. Winokur

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Immunosuppressants, Corticosteroids, Chemotherapy, others

Disqualifiers: Immunosuppressive conditions, Neoplastic disease, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a Phase 1, single-site, comparator-controlled, dosage-escalating study of an intramuscularly administered mRNA-LNP vaccine encoding for DCVC H1 HA in up to 50 adult volunteers aged 18 to 49 years, inclusive. This study is designed to assess the safety and immunogenicity of two doses of DCVC H1 HA mRNA vaccine administered 28 days apart. Eligible participants will be sequentially enrolled into dosage escalation groups (10 mcg, 25 mcg, and 50 mcg). A separate group of 10 participants will receive one dose of the licensed quadrivalent influenza vaccine (IIV4). Enrollment of participants into the IIV4 group is limited to when the vaccine is available for a given year. Concurrent enrollment of the IIV4 group and any pre-specified study product group or groups may present logistical challenges due to the availability of the IIV4 vaccine and may preclude enrollment of all study participants prior to the subsequent off-season. Participants receiving IIV4 will be followed for safety but only their immune responses will be compared to those of participants receiving DCVC H1 HA mRNA vaccine. Dosing of DCVC H1 HA mRNA vaccine will commence at the lowest dose (10 mcg) and only escalate to the next highest dose if safety concerns are not identified. For each DCVC H1 HA mRNA vaccine dosing group, the first two participants enrolled will be considered the sentinel subgroup. After the two participants in the Low Dose sentinel subgroup are enrolled and given their first vaccination, enrollment and subsequent vaccinations in that dosing group will then be stopped until Day 3. This review will be conducted by a Safety Review Committee (SRC). If no halting criteria are met, the SRC will allow administration of the second dose for the sentinel subgroup and continued enrollment of the remaining 8 Low Dose Group participants (expanded subgroup) to complete enrollment of 10 participants. In order for a timely receipt of a second dose of study product on Day 29, SRC review and approval must occur prior to Study Day 28 for the first sentinel participant in the Low Dose Group. After the Low Dose Group enrollment is completed and both doses have been administered, enrollment will be stopped pending SRC review. After all participants in the Low Dose Group have completed the Day 36 visit, the SRC will review the clinical laboratory, reactogenicity, and adverse event information through the Day 36 visit for all Low Dose Group participants that received two doses. Approval by the SRC will allow dose escalation and initiation of enrollment of the Medium Dose Group sentinel subgroup. The Medium and High Dose sentinel and expanded groups will be enrolled as described above for the Low Dose sentinel and expanded groups, respectively, with the High Dose expanded subgroup enrolling up to 18 individuals. The primary objective of this study is to assess the safety of two doses of DCVC H1 HA mRNA Vaccine administered intramuscularly in healthy adults (18-49 yrs) at dosage levels of 10 mcg, 25 mcg, and 50 mcg.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like corticosteroids and high-dose inhaled steroids should not be taken within 30 days before the study vaccination. It's best to discuss your specific medications with the trial team.

How is the DCVC H1 HA mRNA vaccine different from other flu treatments?

The DCVC H1 HA mRNA vaccine is unique because it uses a lipid nanoparticle-encapsulated mRNA platform to encode a consensus hemagglutinin (HA) sequence, aiming to provide broad protection against various H1N1 influenza strains, unlike traditional vaccines that target specific strains and may not be as effective due to viral mutations. ^{1 2 3 4 5}

What data supports the effectiveness of the DCVC H1 HA mRNA vaccine for flu?

The research does not provide direct evidence about the effectiveness of the DCVC H1 HA mRNA vaccine for flu, but it does suggest that influenza vaccination in general can lower the risk of certain heart-related issues in patients with chronic obstructive pulmonary disease (COPD). This implies that flu vaccines may have broader health benefits beyond just preventing the flu. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

Healthy adults aged 18-49 with stable blood pressure, not pregnant or breastfeeding, and without significant health conditions can join. They must agree to use contraception and avoid sperm donation for specified periods around vaccination. Exclusions include drug abuse, liver disease, immune disorders, recent corticosteroid use, severe reactions to vaccines, certain heart conditions, psychiatric hospitalization within the past 5 years.

Inclusion Criteria

I can follow the study's procedures and attend all visits.

I agree not to donate sperm and to use contraception for 90 days after my last vaccine dose.

Must agree to collection of venous blood and nasal absorption specimens per protocol and enrollment in DMID 19-0025 biorepository protocol for use of residual blood specimens

Exclusion Criteria

I have had Guillain-Barré Syndrome in the past.

Has a positive urine toxicology screen

I have a history of heart inflammation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of DCVC H1 HA mRNA vaccine administered 28 days apart

4 weeks

2 visits (in-person)

Safety Evaluation

Safety Review Committee evaluates safety data to determine dose escalation

1 week

Follow-up

Participants are monitored for safety and immunogenicity after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• DCVC H1 HA mRNA vaccine
• Quadrivalent Recombinant Seasonal Influenza Vaccine

Trial Overview The trial is testing a new mRNA vaccine (DCVC H1 HA) against H1N1 influenza in healthy adults. Participants will receive varying doses (10 mcg up to an optimal dose determined by safety outcomes) compared with a standard quadrivalent flu vaccine. The study aims to find the safest effective dose.

How Is the Trial Designed?

Group I: Arm 3 Experimental Treatment 2 Interventions

Healthy adults, 18 to 49 years of age will receive 50 mcg of DCVC H1 HA mRNA vaccine administered intramuscularly to the upper arm/deltoid at days 1 and 29. A safety evaluation will occur to ensure the safety data support proceeding to the optimal dose group. N = 20

Group II: Arm 2 Experimental Treatment 2 Interventions

Healthy adults, 18 to 49 years of age will receive 25 mcg of DCVC H1 HA mRNA vaccine administered intramuscularly to the upper arm/deltoid at days 1 and 29. A dose escalation safety evaluation will occur to ensure the safety data support proceeding to the higher dose group. N = 10

Group III: Arm 1 Experimental Treatment 2 Interventions

Healthy adults, 18 to 49 years of age will receive 10 mcg of DCVC H1 HA mRNA Vaccine administered intramuscularly to the upper arm/deltoid at days 1 and 29. A dose escalation safety evaluation will occur to ensure the safety data support proceeding to the higher dose group. N = 10

Group IV: Arm 4 Active Control 3 Interventions

Healthy adults, 18 to 49 years of age will receive 60 mcg of Licensed quadrivalent inactivated influenza vaccine (IIV4), Fluzone Quadrivalent, administered intramuscularly to the upper arm/deltoid once. N = 10

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

In a 6-week study involving 169 patients with mild to moderate asthma, fluticasone propionate (FP) at 2 x 250 micrograms/day was found to be significantly more effective than flunisolide (FLUN) at 2 x 500 micrograms/day, with 79% of FP patients showing improvement compared to 57% for FLUN (p = 0.02).

FP demonstrated greater efficacy in reducing symptoms like dyspnea and cough, particularly in patients with lower lung function (FEV1), while both treatments were generally well-tolerated and deemed safe by the majority of participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Controlled clinical comparative evaluation of fluticasone powder inhalation versus flunisolide dose aerosol in patients with mild to moderate asthma]. Bergmann, KC.[2021]

In a trial involving 106 chronic-progressive patients, Cop 1 showed a lower confirmed progression rate on the disability scale compared to placebo, with 20.4% of Cop 1 patients progressing versus 29.5% in the placebo group over two years.

The study found significant differences in unconfirmed progression rates and progression of 0.5 EDSS units, indicating that Cop 1 may help slow disease progression in chronic-progressive patients, although overall survival curves were not significantly different.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. Bornstein, MB., Miller, A., Slagle, S., et al.[2019]

Influenza vaccination is associated with a significantly lower risk of developing ventricular arrhythmia (VA) in patients with chronic obstructive pulmonary disease (COPD), based on a study of 18,658 patients over 12 years.

Patients with specific health conditions (CHA2DS2-VASc scores of 2-3) who received one or more influenza vaccinations showed even greater reductions in VA risk, suggesting that vaccination could be a beneficial preventive measure for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza Vaccination and the Risk of Ventricular Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease: A Population-Based Longitudinal Study. Chen, CC., Lin, CH., Hao, WR., et al.[2021]

The corrected hypercapnic ventilation response (CHCVR) is a more reliable measure of chemosensitivity in patients with poor lung function, such as those with chronic obstructive pulmonary disease (COPD), compared to the standard hypercapnic ventilation response (HCVR).

In a study involving 34 COPD patients and 19 patients with low FEV1 due to small stature, CHCVR demonstrated high sensitivity (86%) and specificity (100%), indicating it is a valuable tool for assessing respiratory function in ventilation-limited patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypercapnic ventilation response in patients with lung disease: improved accuracy by correcting for ventilation ability. Jones, RL., Neary, JM., Man, GC., et al.[2018]

The IMPACT trial, involving 10,355 patients, showed that the combination therapy of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) significantly reduced the rate of moderate or severe exacerbations in patients with symptomatic COPD compared to other combinations.

Patients using FF/UMEC/VI reported clinically meaningful improvements in health-related quality of life and symptoms, as measured by the St George's Respiratory Questionnaire and other assessments, over 52 weeks, indicating its efficacy as a once-daily treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Inhaler Triple Therapy and Health-Related Quality of Life in COPD: The IMPACT Study. Tabberer, M., Jones, CE., Kilbride, S., et al.[2022]

The study developed a lipid nanoparticle-encapsulated mRNA vaccine targeting a consensus hemagglutinin (HA) sequence, which showed strong immunogenicity and protective efficacy against various H1N1 influenza viruses in mice after two doses.

The H1c-mRNA-LNP vaccine induced robust antibody responses and both Th1 and Th2 cellular immune responses, with a stronger Th1 response, suggesting it could be a promising candidate for a broadly protective influenza vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of an mRNA vaccine against a panel of heterologous H1N1 seasonal influenza viruses using a consensus hemagglutinin sequence. Ma, N., Xia, ZW., Zhang, ZG., et al.[2023]

The novel combined mRNA vaccine AR-CoV/IAV, which targets both COVID-19 and influenza A, successfully generated strong immune responses in mice, producing protective antibodies and cellular immunity against both viruses.

Immunization with AR-CoV/IAV effectively protected mice from severe outcomes associated with coinfection of influenza A and SARS-CoV-2 variants, demonstrating the potential of this vaccine platform for preventing respiratory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rational development of a combined mRNA vaccine against COVID-19 and influenza. Ye, Q., Wu, M., Zhou, C., et al.[2023]

An mRNA lipid nanoparticle vaccine targeting the hemagglutinin glycoprotein from the highly pathogenic H5 clade 2.3.4.4b avian influenza virus has been developed and shown to be immunogenic in both mice and ferrets.

The vaccine effectively prevents illness and death in ferrets after exposure to the H5N1 virus, indicating its potential as a protective measure against this strain of avian influenza.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus. Furey, C., Ye, N., Kercher, L., et al.[2023]

A combined mRNA-LNP vaccine targeting four different influenza A antigens was shown to effectively induce strong immune responses in mice after just one dose, demonstrating its potential for a universal influenza vaccine.

The quadrivalent formulation provided protection against various influenza viruses, including a challenging H1N1 strain, with minimal side effects, indicating its efficacy and safety at a low antigen dose of 125 ng per component.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses. McMahon, M., O'Dell, G., Tan, J., et al.[2023]

A new influenza virus vaccine candidate using nucleoside-modified mRNA encoding the hemagglutinin (HA) stalk has shown promise in inducing strong antibody responses in mice, rabbits, and ferrets.

Immunization with this HA mRNA vaccine not only generated antibodies against the HA stalk but also provided protection against various strains of influenza, indicating its potential as a broadly protective vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. Pardi, N., Parkhouse, K., Kirkpatrick, E., et al.[2020]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

[Controlled clinical comparative evaluation of fluticasone powder inhalation versus flunisolide dose aerosol in patients with mild to moderate asthma]. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Influenza Vaccination and the Risk of Ventricular Arrhythmias in Patients With Chronic Obstructive Pulmonary Disease: A Population-Based Longitudinal Study. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Hypercapnic ventilation response in patients with lung disease: improved accuracy by correcting for ventilation ability. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Single-Inhaler Triple Therapy and Health-Related Quality of Life in COPD: The IMPACT Study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Development of an mRNA vaccine against a panel of heterologous H1N1 seasonal influenza viruses using a consensus hemagglutinin sequence. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Rational development of a combined mRNA vaccine against COVID-19 and influenza. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies. [2020]