Safety and Immunogenicity Study of Self-Amplifying RNA Pandemic Influenza Vaccine in Adults

Phase 1

Not yet recruiting

• Conditions: Influenza, Human
• Interventions: Biological: ARCT-2304; Biological: Control vaccine younger adults; Biological: Control vaccine older adults; Other: Placebo Vaccine

• Registration Number: NCT06602531
• Lead Sponsor: Arcturus Therapeutics, Inc.

Brief Summary

The goal of this clinical trial is to evaluate the safety and immune responses of three different dose levels a self-amplifying RNA pandemic influenza vaccine (ARCT-2304) in adults. The key objectives of the study are:

* To evaluate safety and reactogenicity of different dose levels of the ARCT-2304 vaccine

* To describe the Immune responses of different dose levels of the ARCT-2304 vaccine as measured by hemagglutination inhibition (HAI) and neuraminidase enzyme-linked lectin (ELLA) antibody responses

Researchers will compare the results with licensed influenza vaccines to select the most optimal dose level and schedule for vaccine administration in terms of safety and immunogenicity for further development of the vaccine.

Participants will receive 2 doses of the ARCT-2304 vaccine or 1 dose of licensed influenza vaccine and 1 dose of placebo.

They will be asked:

* to complete a daily diary for 7 days after each vaccination, answering questions how they have been feeling on that day.

* to provide blood samples at each visit in the clinic

* to comply with all study visits and procedures (e.g., be available for planned telephone contacts and unscheduled clinic visits, if required)

Detailed Description

Phase 1, first-in-human, randomized, controlled, observer blind, dose level and schedule-finding study, to evaluate the safety, reactogenicity, and immunogenicity of a self-amplifying mRNA pandemic influenza (H5N1) vaccine (ARCT-2304) when administered as a 2-dose vaccination series to healthy adults in comparison with an inactivated influenza vaccine.

Study drug (ARCT-2304 or control) will be administered as a 2-dose vaccination series as an intramuscular (IM) injection. The study comprises two parts.

In Part 1, 120 participants (young adults) will be randomized to one of the three dose levels of the ARCT-2304 vaccine or control vaccine. Participants will be further randomized to one of the two different vaccination schedules.

In Part 2, 80 participants (older adults) will be randomized to one of the three dose levels of the ARCT-2304 vaccine or control vaccine. Participants will be further randomized to one of the two different vaccination schedules.

Investigational Vaccine: ARCT-2304

Control Vaccines: licensed influenza vaccines

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-16
• Study First Submitted QC: 2024-09-17
• Last Update Submitted: 2024-09-17
• Study First Posted: 2024-09-19
• Last Update Posted: 2024-09-19
• Study Start: 2024-12-12
• Primary Completion: 2025-07-21
• Study Completion: 2025-12-19

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Individuals are male or female adults 18-80 years of age.
• Healthy participants or participants with pre-existing stable medical conditions.
• Individuals of childbearing potential must be willing to adhere to contraceptive requirements.

Main

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Exclusion Criteria

• Individuals with acute medical conditions or febrile illness, including body temperature ≥100.4°F (≥38.0°C measured by any method) within 3 days prior to randomization.
• Individuals with a known history of severe hypersensitivity reactions, including anaphylaxis, or other significant adverse reactions to any mRNA vaccine, influenza vaccine, or excipients.
• Individuals with a history of myocarditis, pericarditis, myopericarditis, or cardiomyopathy.
• Individuals who received any influenza vaccine within 3 months prior to first vaccine administration or plan to receive an influenza vaccine during the study period.
• Individuals who have received mRNA vaccination within 60 days before the first vaccine administration.
• Individuals who have received or plan to receive an A/H5N1 influenza vaccine and/or individuals who had substantial exposure to or direct contact with poultry, wild birds, live cattle, or raw milk.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low dose of ARCT-2304, Schedule 1, Young Adults	ARCT-2304	Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Mid dose of ARCT-2304, Schedule 1, Young Adults	ARCT-2304	Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
High dose of ARCT-2304, Schedule 1, Young Adults	ARCT-2304	High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Control, Schedule 1, Young Adults	Control vaccine younger adults	Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: Comparator vaccine younger adult and saline placebo vaccine
Control, Schedule 1, Young Adults	Placebo Vaccine	Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: Comparator vaccine younger adult and saline placebo vaccine
Low dose of ARCT-2304, Schedule 1, Older Adults	ARCT-2304	Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Mid dose of ARCT-2304, Schedule 1, Older Adults	ARCT-2304	Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
High dose of ARCT-2304, Schedule 1, Older Adults	ARCT-2304	High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Control, Schedule 1, Older Adults	Control vaccine older adults	Older Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: Comparator vaccine older adult and saline
Control, Schedule 1, Older Adults	Placebo Vaccine	Older Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: Comparator vaccine older adult and saline
Low dose of ARCT-2304, Schedule 2, Young Adults	ARCT-2304	Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Mid dose of ARCT-2304, Schedule 2, Young Adults	ARCT-2304	Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
High dose of ARCT-2304, Schedule 2, Young Adults	ARCT-2304	High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Control, Schedule 2, Young Adults	Control vaccine younger adults	Young Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: Comparator vaccine younger adult and saline placebo vaccine
Control, Schedule 2, Young Adults	Placebo Vaccine	Young Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: Comparator vaccine younger adult and saline placebo vaccine
Low dose of ARCT-2304, Schedule 2, Older Adults	ARCT-2304	Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Mid dose of ARCT-2304, Schedule 2, Older Adults	ARCT-2304	Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
High dose of ARCT-2304, Schedule 2, Older Adults	ARCT-2304	High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Control, Schedule 2, Older Adults	Control vaccine older adults	Older Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: Comparator vaccine older adult and saline placebo vaccine
Control, Schedule 2, Older Adults	Placebo Vaccine	Older Adults Control Vaccine (dose 1) and placebo (dose 2) administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: Comparator vaccine older adult and saline placebo vaccine

Primary Outcome Measures

Name	Time	Method
Percentage of participants reporting local Adverse Events	For 7 days following each study vaccination	Solicited local AEs including injection site pain, erythema, and swelling
Percentage of participants reporting systemic Adverse Events	For 7 days following each study vaccination	Solicited systemic AEs including fatigue, headache, myalgia, arthralgia, nausea, dizziness, chills, and fever
Percentage of participants reporting unsolicited Adverse Events	For 28 days following each study vaccination	Spontaneously reported adverse events and as elicited by investigational site staff
Percentage of participants reporting laboratory or vital signs abnormalities	For 28 days following each study vaccination	Abnormal clinically significant values
Percentage of participants reporting serious adverse events, medically attended adverse events, adverse events of special interest, and adverse events leading to early termination	For 28 days following each study vaccination	Spontaneously reported adverse events and as elicited by investigational site staff
Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein	For 28 days following study second vaccination	HAI antibody levels expressed as GMT, GMFRs, SCRs, and HAI titers
Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins	For 28 days following study second vaccination	ELLA antibody levels expressed as GMT, GMFRs, SCRs, and HAI titers

Secondary Outcome Measures

Name	Time	Method
Percentage of participants reporting serious adverse events, medically attended adverse events, adverse events of special interest, and adverse events leading to early termination	For 240 days following study vaccination	Spontaneously reported adverse events and as elicited by investigational site staff
Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein	For 240 days following study vaccination	HAI antibody levels expressed as GMT, GMFRs, SCRs and HAI titers
Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins	For 240 days following study vaccination	ELLA antibody levels expressed as GMT, GMFRs, SCRs and HAI titers
Serum neutralizing (MN) antibody levels against the HA glycoprotein	For 28 days following study second vaccination	MN antibody levels expressed as GMT, GMFRs, SCRs, and MN titers