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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19; Corona Virus Infection; SARS-CoV-2 Infection
• Intervention / Treatment: Biological: ARCT-165; Biological: ARCT-154; Biological: ARCT-021

Detailed Description

The study will initially enroll approximately 72 adult participants into 2 cohorts (A and B). Cohort A is further sub-divided into two sub-cohorts which include 12 participants who are seronegative, not previously vaccinated at screening (Sub-cohort A1) and 24 participants who are seropositive, not previously vaccinated at screening (Sub-cohort A2).

Within the first cohort (Cohort A), Sub-cohort A1 will include a total of 12 adult participants ≥21 to ≤65 years of age who have not been previously vaccinated with a SARS-CoV-2 vaccine. Sub-cohort A2 will include a total of 24 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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Arcturus Investigational Site 101
• South Africa
  • Soweto
    • Diepkloof, Soweto, South Africa, 1862
      • Arcturus Investigational Site 301
• United States
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Arcturus Investigational Site 202
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Arcturus Investigational Site 201

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Individuals who:

1. Are able to provide consent
2. Agree to comply with all study visits and procedures
3. Are willing and able to adhere to study restrictions
4. Are sexually active and willing to adhere to contraceptive requirements
5. Are male, female, or transgender ≥21 to ≤80 years of age
6. 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:

1. For the unvaccinated groups only, previously received any investigational or authorized MERS-CoV, SARS-CoV, and SARS-CoV-2 vaccines (including ARCT-021)
2. For the previously vaccinated groups only, previously received BNT162b2 but have not received 2 doses within at least 5 months prior to study enrollment
3. Are planning to receive other COVID-19 vaccines during the study period
4. Recently received other vaccines
5. Have a fever or are feeling sick close to the time of the first study vaccination
6. Have a known history of COVID-19 disease or asymptomatic SARS-CoV-2 infection
7. Are pregnant or breastfeeding
8. Have had a severe reaction to previous vaccines
9. Have a severe or uncontrolled disease(s) that may interfere with the interpretation of the study
10. Have some respiratory diseases
11. Have some significant heart diseases
12. Have some neurological conditions
13. Have sickle cell disease or some other blood disorders
14. Have had a major surgery within the past 6 months
15. Have a history of chronic liver disease
16. Have a history of autoimmune disease or immunodeficiency
17. Have received allergy injections, interferon, immunomodulators, cytotoxic drugs or other similar toxic drugs.
18. Have received blood products
19. Have a positive test for hepatitis B or C or human immunodeficiency virus
20. Have uncontrolled hypertension
21. Have had cancer except for cancers that were treated and that have low risk of returning
22. Are obese
23. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group 1, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-165; Participants will receive one dose of ARCT-165 on Day 1 and one dose of ARCT-165 on Day 29	Biological: ARCT-165; Dose 3
Experimental: Study Group 2, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-154; Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29	Biological: ARCT-154; Dose 2
Experimental: Study Group 3, Adult Participants Seronegative, Not Previously Vaccinated to receive ARCT-021; Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29	Biological: ARCT-021; Dose 1
Experimental: Study Group 4, Adult Participants Seropositive, Not Previously Vaccinated to receive ARCT-021; Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29	Biological: ARCT-021; Dose 1
Experimental: Study Group 5, Adult Participants Seropositive, Not Previously Vaccinated randomized to ARCT-154; Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29	Biological: ARCT-154; Dose 2
Experimental: Study Group 6, Adult Participants Previously Vaccinated randomized to receive ARCT-165; Participants will receive one dose of ARCT-165 on Day 1	Biological: ARCT-165; Dose 3
Experimental: Study Group 7, Adult Participants Previously Vaccinated randomized to receive ARCT-154; Participants will receive one dose of ARCT-154 on Day 1	Biological: ARCT-154; Dose 2
Experimental: Study Group 8, Adult Participants Previously Vaccinated randomized to receive ARCT-021; Participants will receive one dose of ARCT-021 on Day 1	Biological: ARCT-021; Dose 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Solicited Local or Systemic Adverse Events (AEs)	Solicited local AEs were defined as injection site erythema, injection site pain, injection site induration, and injection site tenderness. Solicited systemic AEs were defined as arthralgia, chills, diarrhea, dizziness, fatigue, fever (categorized by measured body temperature), headache, myalgia, nausea and vomiting. Data are reported for the number of participants with solicited local and solicited systemic AEs. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Day 8 (7 days after first vaccine administration for Cohorts A1, A2 and B), and up to Day 36 (7 days after second vaccine administration for Cohorts A1 and A2)
Number of Participants Reporting Unsolicited AEs	Unsolicited AEs were defined as any spontaneously reported or discovered AE. Data are reported for the number of participants with unsolicited AEs. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to Day 29 (28 days after vaccine administration for Cohort B), and up to Day 57 (up to 28 days after each vaccine administration for Cohorts A1 and A2)
Number of Participants Reporting Medically Attended Adverse Events (MAAEs), AEs Leading to Discontinuation From Study Vaccine/Study Withdrawal, or Serious Adverse Events (SAEs)	An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) with a health care provider (HCP) (e.g., nurse, nurse practitioner, physician's assistant, physician), including visits to a study site for unscheduled assessments (e.g., rash assessment, abnormal laboratory follow up, coronavirus disease 2019 [COVID-19]) and visits to HCPs external to the study site (e.g., urgent care, primary care physician). An SAE was defined as any event that resulted in death, was immediately life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Through Final Visit (365 days after last study vaccine dose); up to a maximum of approximately 394 days
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Serum Neutralizing Antibody Levels, Expressed as Geometric Mean Concentration (GMC)	Blood samples were collected to assess participants' immune response. GMC data are reported for the pseudoviral D614G variant. Data are reported in international units per milliliter (IU/mL).	Baseline, Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2; Baseline, Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
SARS-CoV-2 Serum Neutralizing Antibody Levels, Expressed as GMC	Blood samples were collected to assess participants' immune response. GMC data are reported for the pseudoviral B.1.351 (beta) variant. Data are reported in arbitrary units per milliliter (AU/mL).	Baseline, Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2; Baseline, Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
SARS-CoV-2 Serum Neutralizing Antibody Levels, Expressed as Geometric Mean Fold Rise (GMFR)	Blood samples were collected to assess participants' immune response. GMFR data are reported for the pseudoviral D614G variant.	Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2, and Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
SARS-CoV-2 Serum Neutralizing Antibody Levels, Expressed as GMFR	Blood samples were collected to assess participants' immune response. GMFR data are reported for the pseudoviral B.1.351 (beta) variant.	Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2, and Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
Number of Participants Achieving Greater Than or Equal to 4-fold Rise From Before Vaccination in SARS-CoV-2 Serum Neutralizing Antibody Levels (Pseudoviral D614G Variant)	Blood samples were collected to assess participants' immune response. Data are reported for the pseudoviral D614G variant.	Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2, and Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
Number of Participants Achieving Greater Than or Equal to 4-fold Rise From Before Vaccination in SARS-CoV-2 Serum Neutralizing Antibody Levels (Pseudoviral B.1.351 [Beta] Variant)	Blood samples were collected to assess participants' immune response. Data are reported for the pseudoviral B.1.351 (beta) variant.	Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2, and Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
GMC Ratio (ARCT-165 vs ARCT-154 and ARCT-021 vs ARCT-154)	Blood samples were collected to assess participants' immune response. Data are reported for the pseudoviral D614G Variant, B.1.351 Variant, B.1.617.2 Variant, BA.1 Variant for the GMC ratio of ARCT-165 vs ARCT-154 and ARCT-021 vs ARCT-154. Data are reported for the ARCT-165 and ARCT-021 arms (vs ARCT-154 values).	Days 29, 57, 209, Final Visit (approx. Day 394) for Cohorts A1 and A2, and Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
GMC Ratio (ARCT-021 vs ARCT-165 Cohorts A1 and B)	Blood samples were collected to assess participants' immune response. Data are reported for the pseudoviral D614G Variant, B.1.351 Variant, B.1.617.2 Variant, BA.1 Variant for the GMC ratio of ARCT-021 vs ARCT-165. Data are reported for the ARCT-021 arm (vs ARCT-165 values).	Days 29, 57, 209, Final Visit (approx. Day 394) for Cohort A1, and Days 15, 29, 91, 181, 271 and Final Visit (approx. Day 366) for Cohort B
SARS-CoV-2 Full-length Spike and Receptor-binding Domain (RBD) Binding Antibody Levels, Expressed as GMCs	Spike binding antibody levels expressed as GMCs are reported for ancestral, D614G, and B.1.351 variants and RBD binding antibodies for ancestral strain.	Baseline and Day 57 for Cohorts A1 and A2, Baseline and Day 15 for Cohort B
Changes in SARS-CoV-2 Full-length Spike and RBD Binding Antibody Levels, Expressed as GMFRs	Spike binding antibody levels expressed as GMFRs are reported for ancestral, D614G, and B.1.351 variants and RBD binding antibody levels expressed as GMFR for ancestral strain.	Day 57 for Cohorts A1 and A2, Day 15 for Cohort B
Number of Participants Achieving Greater Than or Equal to 4-fold Rise From Before Vaccination in SARS-CoV-2 Full-length Spike and RBD Binding Antibody Levels	Data are reported for ancestral, D614G, and B.1.351 variants for Spike binding antibodies and ancestral for RBD binding antibodies.	Day 57 for Cohorts A1 and A2, Day 15 for Cohort B

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.
• Investigators: Study Director: Clinical Program Director, Arcturus Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2021
• Primary Completion (Actual): December 19, 2023
• Study Completion (Actual): December 19, 2023

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: September 30, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: SARS-CoV-2 Vaccine; Coronavirus Virus Diseases; RNA COVID-19; COVID-19 Vaccine Arcturus; Self Amplifying RNA Vaccine; Variants of Concern
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronaviridae Infections; Nidovirales Infections; COVID-19; Coronavirus Infections; ARCT-154 vaccine
• Other Study ID Numbers: ARCT-165-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will only be made available to study investigators at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No