A Phase 1, First-in-human, Randomized, Observer-blind, Parallel Design, Controlled, Dose Level and Schedule-finding Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of a Self-Amplifying mRNA Pandemic Influenza Vaccine (ARCT-2304) When Administered to Healthy Adults
Overview
- Phase
- Phase 1
- Intervention
- ARCT-2304
- Conditions
- Influenza, Human
- Sponsor
- Arcturus Therapeutics, Inc.
- Enrollment
- 212
- Locations
- 4
- Primary Endpoint
- Percentage of participants reporting local Adverse Events
- Status
- Completed
- Last Updated
- 29 days ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •Main 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.
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.
Arms & Interventions
High dose of ARCT-2304, Schedule 1, Older Adults
High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
High dose of ARCT-2304, Schedule 1, Young Adults
High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Control, Schedule 1, 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
Intervention: Control vaccine (licensed seasonal influenza vaccine) older adults
Control, Schedule 2, Young 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
Intervention: Control vaccine (licensed seasonal influenza vaccine) younger adults
Control, Schedule 2, 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
Intervention: Control vaccine (licensed seasonal influenza vaccine) older adults
Control, Schedule 1, Young 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
Intervention: Control vaccine (licensed seasonal influenza vaccine) younger adults
Control, Schedule 1, Young 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
Intervention: Placebo Vaccine
Control, Schedule 1, 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
Intervention: Placebo Vaccine
Control, Schedule 2, Young 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
Intervention: Placebo Vaccine
Control, Schedule 2, 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
Intervention: Placebo Vaccine
Low dose of ARCT-2304, Schedule 2, Older Adults
Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Mid dose of ARCT-2304, Schedule 2, Older Adults
Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Low dose of ARCT-2304, Schedule 1, Young Adults
Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Mid dose of ARCT-2304, Schedule 1, Young Adults
Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Low dose of ARCT-2304, Schedule 1, Older Adults
Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Mid dose of ARCT-2304, Schedule 1, Older Adults
Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 1 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Low dose of ARCT-2304, Schedule 2, Young Adults
Low dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Mid dose of ARCT-2304, Schedule 2, Young Adults
Mid dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
High dose of ARCT-2304, Schedule 2, Young Adults
High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
High dose of ARCT-2304, Schedule 2, Older Adults
High dose of ARCT-2304 administered through intramuscular injection in the deltoid muscle. Interventions: 2-dose regimen, schedule 2 Investigational Vaccine: ARCT-2304
Intervention: ARCT-2304
Outcomes
Primary Outcomes
Percentage of participants reporting local Adverse Events
Time Frame: For 7 days following each study vaccination
Solicited local AEs including injection site pain, erythema, and swelling
Percentage of participants reporting systemic Adverse Events
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: For 28 days following study second vaccination
ELLA antibody levels expressed as GMT, GMFRs, SCRs, and HAI titers
Secondary Outcomes
- Serum neuraminidase enzyme-linked lectin (ELLA) assay antibody levels against the NA glycoproteins(For 240 days following study vaccination)
- Serum neutralizing (MN) antibody levels against the HA glycoprotein(For 28 days following study second vaccination)
- 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)
- Serum hemagglutination inhibition (HAI) antibody levels against the HA glycoprotein(For 240 days following study vaccination)