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

Phase 1

Completed

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

Interventions: Biological: ARCT-021
Biological: ARCT-154
Biological: ARCT-165

Registration Number: NCT05037097

Lead Sponsor: Arcturus Therapeutics, Inc.

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Group 4, Adult Participants Seropositive, Not Previously Vaccinated to receive ARCT-021	ARCT-021	Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29
Study Group 2, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-154	ARCT-154	Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29
Study Group 7, Adult Participants Previously Vaccinated randomized to receive ARCT-154	ARCT-154	Participants will receive one dose of ARCT-154 on Day 1
Study Group 1, Adult Participants Seronegative, Not Previously Vaccinated randomized to ARCT-165	ARCT-165	Participants will receive one dose of ARCT-165 on Day 1 and one dose of ARCT-165 on Day 29
Study Group 6, Adult Participants Previously Vaccinated randomized to receive ARCT-165	ARCT-165	Participants will receive one dose of ARCT-165 on Day 1
Study Group 5, Adult Participants Seropositive, Not Previously Vaccinated randomized to ARCT-154	ARCT-154	Participants will receive one dose of ARCT-154 on Day 1 and one dose of ARCT-154 on Day 29
Study Group 8, Adult Participants Previously Vaccinated randomized to receive ARCT-021	ARCT-021	Participants will receive one dose of ARCT-021 on Day 1
Study Group 3, Adult Participants Seronegative, Not Previously Vaccinated to receive ARCT-021	ARCT-021	Participants will receive one dose of ARCT-021 on Day 1 and one dose of ARCT-021 on Day 29

Primary Outcome Measures

Name	Time	Method
Number of Participants Reporting Solicited Local or Systemic Adverse Events (AEs)	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)	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.
Number of Participants Reporting Unsolicited AEs	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)	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.
Number of Participants Reporting Medically Attended Adverse Events (MAAEs), AEs Leading to Discontinuation From Study Vaccine/Study Withdrawal, or Serious Adverse Events (SAEs)	Through Final Visit (365 days after last study vaccine dose); up to a maximum of approximately 394 days	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.
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) Serum Neutralizing Antibody Levels, Expressed as Geometric Mean Concentration (GMC)	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	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).
SARS-CoV-2 Serum Neutralizing Antibody Levels, Expressed as GMC	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	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).
SARS-CoV-2 Serum Neutralizing Antibody Levels, Expressed as Geometric Mean Fold Rise (GMFR)	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	Blood samples were collected to assess participants' immune response. GMFR data are reported for the pseudoviral D614G variant.
SARS-CoV-2 Serum Neutralizing Antibody Levels, Expressed as GMFR	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	Blood samples were collected to assess participants' immune response. GMFR data are reported for the pseudoviral B.1.351 (beta) variant.
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)	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	Blood samples were collected to assess participants' immune response. Data are reported for the pseudoviral D614G variant.
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)	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	Blood samples were collected to assess participants' immune response. Data are reported for the pseudoviral B.1.351 (beta) variant.
GMC Ratio (ARCT-165 vs ARCT-154 and ARCT-021 vs ARCT-154)	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	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).
GMC Ratio (ARCT-021 vs ARCT-165 Cohorts A1 and B)	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	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).
SARS-CoV-2 Full-length Spike and Receptor-binding Domain (RBD) Binding Antibody Levels, Expressed as GMCs	Baseline and Day 57 for Cohorts A1 and A2, Baseline and Day 15 for Cohort B	Spike binding antibody levels expressed as GMCs are reported for ancestral, D614G, and B.1.351 variants and RBD binding antibodies for ancestral strain.
Changes in SARS-CoV-2 Full-length Spike and RBD Binding Antibody Levels, Expressed as GMFRs	Day 57 for Cohorts A1 and A2, Day 15 for Cohort B	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.
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	Day 57 for Cohorts A1 and A2, Day 15 for Cohort B	Data are reported for ancestral, D614G, and B.1.351 variants for Spike binding antibodies and ancestral for RBD binding antibodies.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (4): Arcturus Investigational Site 202
🇺🇸
Wichita, Kansas, United States
Arcturus Investigational Site 201
🇺🇸
Kansas City, Missouri, United States
Arcturus Investigational Site 101
🇸🇬
Singapore, Singapore
Arcturus Investigational Site 301
🇿🇦
Diepkloof, Soweto, South Africa
Arcturus Investigational Site 202
🇺🇸Wichita, Kansas, United States