Phase 2a study of the safety and efficacy of the vaccines modRNA and saRNA in an influenza challenge
Research type
Research Study
Full title
A Phase 2a, Randomised, Double-blind, External Placebo-controlled and Internal Comparator-controlled Study to Evaluate the Safety, Immunogenicity, and Efficacy of Influenza Virus Vaccines (modRNA and saRNA) in a Human Viral Challenge Model in Healthy Adult Participants
IRAS ID
1006279
Contact name
Alex Mann
Contact email
Sponsor organisation
hVIVO Services Ltd.
ISRCTN Number
ISRCTN13789612
Research summary
The purpose of this study is to investigate the efficacy and safety of vaccination with Nucleoside-modified Messenger Ribonucleic Acid (ModRNA) and Self-amplifying Ribonucleic Acid (SaRNA) vaccines in preventing infection with A/Delaware/55/2019 (H1N1) influenza virus compared to an external placebo group and a licenced flu vaccine (quadrivalent influenza vaccines (QIV)). Up to 240 participants will be enrolled onto the study. Each participant will remain in the study for about 5 months from screening until their last follow-up visit.
The study is divided into 4 phases:
1) Screening phase: Screening will occur between Day -90 to Day -30. Historical generic screening data collected through the hVIVO generic screening process may be transferred to this study after the study-specific consent form has been signed by the participant.
2) Vaccination phase: Participants will be invited to clinic to be randomly allocated to receive a single intramuscular dose of either:
Part A: QIV or Monovalent modRNA vaccine preparation.
Part B: 2 out 3 of the following; bivalent saRNA vaccine, monovalent saRNA vaccine or a bivalent modRNA vaccine preparations will be used.
Participants are invited to attend clinic visits 1, 3 and 8 days after vaccination, with a telephone follow-up 14 days post vaccination.
3) Quarantine phase: Participants will stay in the quarantine unit for approximately 11 days (from Day -2 to Day 8). Two days prior to the day of inoculation with influenza, participants will be admitted to quarantine where their eligibility will be reassessed and inoculated with influenza on day 0. Participants will undergo a range of clinical assessments and safety monitoring for the entirety of their stay in quarantine. Participants will be discharged from the quarantine unit on Day 8.
4) Outpatient phase: Final follow-up visit 28 days (±3 days) after the day they receive the virus. Their symptoms will be reassessed, and a complete safety examination performed.Lay Summary of Results
This study tested different types of flu vaccines to see how well they protected people from a specific flu virus (Influenza A/H1N1). The study included several groups of participants who received different vaccines, as well as a separate group that did not receive a study vaccine.
Who Took Part in the Study?
Participants were divided into different vaccine groups:
• Monovalent modRNA vaccine (a single-strain influenza A/H1N1 mRNA vaccine) – 74 participants
• Quadrivalent Influenza Vaccine (QIV) comparator (a standard flu vaccine) – 75 participants
• Bivalent saRNA vaccine (a self-amplifying RNA vaccine encoding two antigens from a single strain) – 69 participants
• Bivalent modRNA vaccine (a mRNA vaccine encoding two antigens from a single strain) – 67 participants[LK2.1][SA2.2][AG2.3]
Another 54 participants were in a separate group from a previous study. These individuals were not vaccinated in this study but were included in the data analysis for comparison.
What Happened in the Study?
• After vaccination, most participants were exposed to the flu virus to test how well the vaccines worked.
• Most participants completed the study, with over 98% of the external placebo group and between 64% and 78% of the vaccinated groups in this study staying until the end.
• Participants in all groups had similar characteristics in terms of age, ethnicity, and body weight. However, there were slightly more women in the QIV comparator group.
Did the Vaccines Work?
The study measured how much flu virus was present in participants after they were exposed.• The monovalent modRNA, bivalent saRNA, and bivalent modRNA vaccines significantly reduced the amount of virus in the body compared to the placebo group.
• The bivalent modRNA vaccine showed the greatest reductions in the amount of virus.
• All vaccine groups met international criteria for producing a strong immune response, meaning at least 40% of participants had increased levels of flu-fighting antibodies [AG3.1]and over 70% had protective levels of immunity.Was the Vaccine Safe?
• The vaccines were safe and well tolerated. No participants had life-threatening reactions or serious side effects.
• Some participants experienced health problems during the study. These may or may not have been related to the study medicine. Most were mild and went away by the end of the study.
• Laboratory markers were monitored in all participants throughout the study. Some participants in the bivalent modRNA and bivalent saRNA groups experienced temporary reductions in a type of white blood cell (neutropenia) and temporary increases in inflammation markers (C-reactive protein), but these changes were not associated with any abnormal effects. All events resolved without any lasting issues.[AG4.1]Overall Findings
• The monovalent modRNA, bivalent saRNA, and bivalent modRNA vaccines effectively protected against flu infection, reduced the severity of symptoms, and lowered the amount of flu virus in the body.
• All vaccines were safe, and most side effects were mild and temporary.Has the registry been updated to include summary results?: Yes
If yes - please enter the URL to summary results: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.isrctn.com%252FISRCTN13789612%253Fq%253DISRCTN13789612%2526filters%253D%2526sort%253D%2526offset%253D1%2526totalResults%253D1%2526page%253D1%2526pageSize%253D10%2FNBTI%2F4di_AQ%2FAQ%2F750d390b-ba15-4bcf-8681-423a36c24ab8%2F1%2FgcrtUHQAMM&data=05%7C02%7Csurreyborders.rec%40hra.nhs.uk%7Ce01b5d6d22964f39213908ddc9199a75%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638887833988231845%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=TNSiPZxq1uPz0erek%2FQwpJtdMDS7e1RcJT7SqCpFe5I%3D&reserved=0
If no – why not?:
Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Pending
If yes, describe or provide URLs to disseminated materials:
If pending, date when dissemination is expected: 01/12/2025
If no, explain why you didn't follow it:
Have participants been informed of the results of the study?: Pending
If yes, describe and/or provide URLs to materials shared and how they were shared:
If pending, date when feedback is expected: 30/08/2025
If no, explain why they haven't:
Have you enabled sharing of study data with others?: No
If yes, describe or provide URLs to how it has been shared:
If no, explain why sharing hasn't been enabled: N/A
Have you enabled sharing of tissue samples and associated data with others?: No
If yes, describe or provide a URL:
If no, explain why: N/A
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London - Surrey Borders Research Ethics Committee
REC reference
22/LO/0742
Date of REC Opinion
9 Dec 2022
REC opinion
Further Information Favourable Opinion