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

NCT05037097 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ARCT-165-01
• Study Type: interventional
• Target: 72
• Locations: 3 countries
• Sites: 4

Brief Summary

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.

Conditions

COVID-19; SARS-CoV-2 Infection; Corona Virus Infection

Keywords

SARS-CoV-2 Vaccine; Coronavirus Virus Diseases; RNA COVID-19; COVID-19 Vaccine Arcturus; Self Amplifying RNA Vaccine; Variants of Concern

Outcome Measures

Primary Outcomes (14)

• 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

Study Arms (8)

Study Group 1, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-165

EXPERIMENTAL

Participants will receive one dose of ARCT-165 on Day 1 and one dose of ARCT-165 on Day 29

Biological: ARCT-165

Study Group 2, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-154

EXPERIMENTAL

Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29

Biological: ARCT-154

Study Group 3, Adult Participants Seronegative, Not Previously Vaccinated to receive ARCT-021

EXPERIMENTAL

Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29

Biological: ARCT-021

Study Group 4, Adult Participants Seropositive, Not Previously Vaccinated to receive ARCT-021

EXPERIMENTAL

Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29

Biological: ARCT-021

Study Group 5, Adult Participants Seropositive, Not Previously Vaccinated randomized to ARCT-154

EXPERIMENTAL

Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29

Biological: ARCT-154

Study Group 6, Adult Participants Previously Vaccinated randomized to receive ARCT-165

EXPERIMENTAL

Participants will receive one dose of ARCT-165 on Day 1

Biological: ARCT-165

Study Group 7, Adult Participants Previously Vaccinated randomized to receive ARCT-154

EXPERIMENTAL

Participants will receive one dose of ARCT-154 on Day 1

Biological: ARCT-154

Study Group 8, Adult Participants Previously Vaccinated randomized to receive ARCT-021

EXPERIMENTAL

Participants will receive one dose of ARCT-021 on Day 1

Biological: ARCT-021

Interventions

ARCT-165 BIOLOGICAL

Dose 3

Study Group 1, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-165; Study Group 6, Adult Participants Previously Vaccinated randomized to receive ARCT-165

ARCT-154 BIOLOGICAL

Dose 2

Study Group 2, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-154; Study Group 5, Adult Participants Seropositive, Not Previously Vaccinated randomized to ARCT-154; Study Group 7, Adult Participants Previously Vaccinated randomized to receive ARCT-154

ARCT-021 BIOLOGICAL

Dose 1

Study Group 3, Adult Participants Seronegative, Not Previously Vaccinated to receive ARCT-021; Study Group 4, Adult Participants Seropositive, Not Previously Vaccinated to receive ARCT-021; Study Group 8, Adult Participants Previously Vaccinated randomized to receive ARCT-021

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arcturus Therapeutics, Inc.: lead

Study Sites (4)

Arcturus Investigational Site 202

Wichita, Kansas, 67207, United States

Location

Arcturus Investigational Site 201

Kansas City, Missouri, 64114, United States

Location

Arcturus Investigational Site 101

Singapore, 169608, Singapore

Location

Arcturus Investigational Site 301

Diepkloof, Soweto, 1862, South Africa

Location

MeSH Terms

Conditions

COVID-19; Coronavirus Infections

Interventions

ARCT-154 vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Arcturus Therapeutics, Inc.
• Organization: Arcturus Therapeutics, Inc.

clinicaltrials@arcturusrx.com

858-900-2660

Study Officials

• Clinical Program Director

  Arcturus Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will evaluate 3 investigational vaccines in parallel.

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 8, 2021
• Study Start: August 30, 2021
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: October 15, 2025
• Results First Posted: October 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (1); US (2); SG (1)