A Trial Evaluating the Safety and Immunogenicity of 3 COVID-19 SARS-CoV-2 RNA Vaccines in Healthy Adults

Study Overview
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Brief Summary
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This is a Phase 1/2, randomized, observer-blind study in healthy adults. The study will evaluate the safety, reactogenicity, and immunogenicity of 3 SARS-CoV-2 self-amplifying RNA vaccine candidates against COVID-19 in adults previously vaccinated and not previously vaccinated against SARS-CoV-2.

Detailed Description
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The study will initially enroll approximately 72 adult participants into 2 cohorts and may expand enrollment up to 144 participants if additional cohorts are added. The first cohort (Cohort A) will include a total of 36 adult participants ≥21 to ≤65 years of age who have not been previously vaccinated with a SARS-CoV-2 vaccine. Study vaccines will be given as 2 doses separated by 28 days. The second cohort (Cohort B) will include a total of 36 adult participants ≥21 to ≤65 years of age who have been previously vaccinated (5 months or longer prior to study enrollment) with SARS-CoV-2 vaccine. Study vaccines will be given as single doses. Additional cohorts may increase the age range of participants up to 80 years of age.

Official Title
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A Phase 1/2 Randomized, Observer-Blind Study of the Safety, Reactogenicity, and Immunogenicity of 3 SARS-CoV-2 RNA Vaccine Candidates in Adults Previously Vaccinated and Not Previously Vaccinated Against SARS-CoV-2

Conditions
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COVID-19, SARS-CoV-2 Infection, Corona Virus Infection

Intervention / Treatment
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* Biological: ARCT-165
* Biological: ARCT-154
* Biological: ARCT-021


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who: Are able to provide consent Agree to comply with all study visits and procedures Are willing and able to adhere to study restrictions Are sexually active and willing to adhere to contraceptive requirements Are male, female, or transgender ≥21 to ≤80 years of age For the previously vaccinated groups only, received 2 doses of SARS-CoV-2 vaccine 5 months or longer prior to study enrollment Exclusion Criteria: Individuals who: For the unvaccinated groups only, previously received any investigational or authorized MERS-CoV, SARS-CoV, and SARS-CoV-2 vaccines (including ARCT-021) For the previously vaccinated groups only, previously received BNT162b2 but have not received 2 doses within at least 5 months prior to study enrollment Are planning to receive other COVID-19 vaccines during the study period Recently received other vaccines Have a fever or are feeling sick close to the time of the first study vaccination Have a known history of COVID-19 disease or asymptomatic SARS-CoV-2 infection Are pregnant or breastfeeding Have had a severe reaction to previous vaccines Have a severe or uncontrolled disease(s) that may interfere with the interpretation of the study Have some respiratory diseases Have some significant heart diseases Have some neurological conditions Have sickle cell disease or some other blood disorders Have had a major surgery within the past 6 months Have a history of chronic liver disease Have a history of autoimmune disease or immunodeficiency Have received allergy injections, interferon, immunomodulators, cytotoxic drugs or other similar toxic drugs. Have received blood products Have a positive test for hepatitis B or C or human immunodeficiency virus Have uncontrolled hypertension Have had cancer except for cancers that were treated and that have low risk of returning Are obese Are Investigator site staff members, employees of Arcturus or the contract research organization (CRO) directly involved in the conduct of the study, or site staff members otherwise supervised by the Investigator or immediate family members of any of the previously mentioned individuals

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will evaluate 3 investigational vaccines in parallel.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group 1, Adult Participants Not Previously Vaccinated randomized to receive ARCT-165<br>Participants will receive one dose of ARCT-165 on Day 1 and one dose of ARCT-165 on Day 29 | Biological: ARCT-165<br>* Dose 3<br>|
| Experimental: Study Group 2, Adult Participants Not Previously Vaccinated randomized to receive ARCT-154<br>Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29 | Biological: ARCT-154<br>* Dose 2<br>|
| Experimental: Study Group 3, Adult Participants Not Previously Vaccinated to receive ARCT-021<br>Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29 | Biological: ARCT-021<br>* Dose 1<br>|
| Experimental: Study Group 4, Adult Participants Previously Vaccinated randomized to receive ARCT-165<br>Participants will receive one dose of ARCT-165 on Day 1 | Biological: ARCT-165<br>* Dose 3<br>|
| Experimental: Study Group 5, Adult Participants Previously Vaccinated randomized to receive ARCT-154<br>Participants will receive one dose of ARCT-154 on Day 1 | Biological: ARCT-154<br>* Dose 2<br>|
| Experimental: Study Group 6, Adult Participants Previously Vaccinated randomized to receive ARCT-021<br>Participants will receive one dose of ARCT-021 on Day 1 | Biological: ARCT-021<br>* Dose 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants reporting solicited local or systemic adverse events | Solicited adverse events reported daily in a diary that reflect generalized symptoms or findings at the injection site following each vaccination | For 7 days following each study vaccination | 
| Percentage of participants reporting unsolicited adverse events | Spontaneously reported adverse events | For 28 days following each study vaccination | 
| Percentage of participants reporting medically attended adverse events | Medically attended adverse event is an AE that leads to an unscheduled visit with a health care provider | Through Final Visit (365 days after last study vaccine dose) | 
| Percentage of participants reporting adverse events leading to discontinuation from study vaccine/study withdrawal | Unsolicited adverse events that meet stopping rules | Through Final Visit (365 days after last study vaccine dose) | 
| Percentage of participants reporting serious adverse events | Unsolicited adverse events that meet the definition of serious | Through Final Visit (365 days after last study vaccine dose) | 
| SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs | Neutralizing antibody response | Through Final Visit (365 days after last study vaccine dose) | 
| Changes in SARS-CoV-2 serum neutralizing levels from before vaccination to each subsequent time point, expressed as GMFRs | Neutralizing antibody response | Through Final Visit (365 days after last study vaccine dose) | 
| Percentages of participants achieving greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels | Neutralizing antibody response | Through Final Visit (365 days after last study vaccine dose) | 
| GMT ratio (ARCT-021/ARCT-165, ARCT-165/ARCT-154, and ARCT-021/ARCT-154) | Neutralizing antibody response | Through Final Visit (365 days after last study vaccine dose) | 
| SARS-CoV-2 full-length spike, RBD, and N binding antibody levels, expressed as GMCs | Binding antibody response | Through Final Visit (365 days after last study vaccine dose) | 
| Changes in SARS-CoV-2 full-length spike, RBD, and N binding antibody levels from before vaccination to each subsequent time point, expressed as GMFRs | Binding antibody response | Through Final Visit (365 days after last study vaccine dose) | 
| Percentages of participants achieving greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 full-length spike, RBD, and N binding antibody levels | Binding antibody response | Through Final Visit (365 days after last study vaccine dose) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 Vaccine, Coronavirus Virus Diseases, RNA COVID-19, COVID-19 Vaccine Arcturus, Self Amplifying RNA Vaccine, Variants of Concern