A Trial Evaluating the Safety and Effects of an RNA Vaccine ARCT-021 in Healthy Adults

A Phase 2 Randomized, Observer-Blind, Placebo-Controlled Study to Assess the Safety, Reactogenicity, and Immunogenicity of the SARS CoV-2 Vaccine ARCT-021 in Healthy Adult Participants

This is a Phase 2, randomized, placebo-controlled, and observer-blind study in healthy adults.

The study will evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 RNA vaccine candidate against COVID-19:

As 2 doses (at two different dose levels), separated by 28 days or as 1 dose

In adults 18 years of age and older

Study Overview

• Status: Terminated
• Conditions: Covid19; Corona Virus Infection; SARS-CoV Infection
• Intervention / Treatment: Biological: ARCT-021 single dose priming; Biological: Randomized booster; Biological: ARCT-021 two lower dose priming; Biological: ARCT-021 two higher dose priming; Biological: Placebo (two doses), priming; Biological: Placebo booster

Detailed Description

This is a multiregional, multicenter, Phase 2, randomized, observer-blind study designed to evaluate the safety, reactogenicity, and immunogenicity of the study vaccine in younger and older adult participants. Enrolled participants will be randomly assigned to receive either study vaccine ARCT-021 or placebo (sterile saline).

Approximately 600 participants (300 each in younger [18 to <56 years of age in United States or 21 to <56 years of age in Singapore] and older [≥56 years of age] participants) will be enrolled (including at least 50% of participants in the older cohort ≥65 years of age). Participants will be stratified by age and then randomly assigned (3 ARCT-021:1 placebo) to receive 2 doses of study vaccine separated by 28 days. At 180 days after second study vaccination (Day 208), participants in Study Groups 1, 2, and 3 will be randomly assigned again to receive a single booster dose of study vaccine (randomly assigned as 1 ARCT-021:1 placebo). Study Group 4 will not be randomized but will receive 1 dose of placebo at Day 208. Study Groups are summarized in Table 1. Study vaccine will be administered in an observer-blind fashion. Participants will be followed for safety and immunogenicity through 180 days after booster vaccination (Day 388). At a subset of clinical sites, all enrolled participants will also undergo blood sampling for evaluation of CMI responses.

Vaccine doses will be assigned as follows:

Younger Age Cohort:

Study Group 1: n= 75 participants, ARCT-021 7.5 µg (first dose), Placebo (second dose Study Group 2: n= 75 participants, ARCT-021 5.0 µg (first dose), 5.0 µg (second dose) Study Group 3: n= 75 participants, ARCT-021 7.5 µg (first dose), 7.5 µg (second dose) Study Group 4: n= 75 participants, Placebo (first dose), Placebo (second dose)

Booster Vaccine:

Study Groups 1, 2, 3: 113 participants, ARCT-021 5.0 µg or 7.5 µg, 112 participants, Placebo Study Group 4: n= 75 participants, Placebo

Older Age Cohort:

Study Group 1: n= 75 participants, ARCT-021 7.5 µg (first dose), Placebo (second dose Study Group 2: n= 75 participants, ARCT-021 5.0 µg (first dose), 5.0 µg (second dose) Study Group 3: n= 75 participants, ARCT-021 7.5 µg (first dose), 7.5 µg (second dose) Study Group 4: n= 75 participants, Placebo (first dose), Placebo (second dose)

Booster Vaccine:

Study Groups 1, 2, 3: 113 participants, ARCT-021 5.0 µg or 7.5 µg, 112 participants, Placebo Study Group 4: n= 75 participants, Placebo

A DSMB will be in place to independently review the safety data of participants. Pausing Rules are also utilized in this study to reduce risk to study participants.

The expected duration of participation for an individual participant is approximately 14 months, inclusive of the Screening period.

• Study Type: Interventional
• Enrollment (Actual): 581
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 117599
    • Arcturus Investigational Site 204
  • Singapore, Singapore, 169608
    • Arcturus Investigational Site 201
  • Singapore, Singapore, 308433
    • Arcturus Investigational Site 203
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Arcturus Investigational Site 103
    • Tucson, Arizona, United States, 85741
      • Arcturus Investigational Site 107
  • California
    • San Diego, California, United States, 92108
      • Arcturus Investigational Site 112
  • Florida
    • Melbourne, Florida, United States, 32934
      • Arcturus Investigational Site 104
    • Orlando, Florida, United States, 32806
      • Arcturus Investigational Site 105
    • Pinellas Park, Florida, United States, 33781
      • Arcturus Investigational Site 106
    • The Villages, Florida, United States, 32162
      • Arcturus Investigational Site 109
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Arcturus Investigational Site 101
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Arcturus Investigational Site 110
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Arcturus Investigational Site 102
  • Texas
    • Austin, Texas, United States, 78705
      • Arcturus Investigational Site 111
    • Dallas, Texas, United States, 75234
      • Arcturus Investigational Site 108

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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 or female ≥18 or (in Singapore) ≥21 years of age
6. are medically stable

Exclusion Criteria:

Individuals who:

1. have had SARS-CoV-2 infection or COVID-19 disease.
2. have had cancer except for cancers that were treated and that have low risk of returning
3. have chronic kidney disease
4. have some chronic lung diseases
5. have some heart conditions
6. have compromised immune systems
7. are obese
8. have sickle cell disease or some other blood disorders
9. are current smokers and/or use illegal drugs
10. have Type 2 diabetics
11. are immunocompromised, immunodeficient or have had a transplant
12. have autoimmune disease
13. have other severe or uncontrolled diseases or disease that may interfere with the interpretation of the study
14. have a positive test for hepatitis B or C or human immunodeficiency virus
15. have had a severe reaction to previous investigational vaccines
16. have a fever or are feeling sick close to the time of the first vaccination of the study
17. have positive drug test at screening
18. are pregnant
19. are breastfeeding
20. have a bleeding disorder
21. have previously received an investigational coronavirus vaccine (SARS-CoV(1) or MERS) or who plan to be in other COVID-19 studies
22. have recently been vaccinated with other vaccines
23. have recently received blood products
24. who work at one of the clinic sites participating in this study, work at Arcturus, who work at other companies that monitor the study or close family members to the sites, Arcturus, or partners involved in study monitoring
25. other restrictions may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group 1, Younger Adult Participants; Participants will receive one dose of ARCT-021 on Day 0, one dose of Placebo (saline) on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo	Biological: ARCT-021 single dose priming; ARCT-021 higher dose (one dose) + placebo (one dose); Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster
Experimental: Study Group 2, Younger Adult Participants; Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo	Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster; Biological: ARCT-021 two lower dose priming; ARCT-021 lower dose (two doses, Day 0 and Day 28)
Experimental: Study Group 3, Younger Adult Participants; Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo	Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster; Biological: ARCT-021 two higher dose priming; ARCT-021 higher dose (two doses, Day 0 and Day 28)
Placebo Comparator: Study Group 4, Younger Adult Participants; Participants will receive one of Placebo (Saline) on Day 0, one dose of Placebo on Day 28, and one dose of Placebo on Day 208	Biological: Placebo (two doses), priming; Placebo (two doses, Day 0 and Day 28); Biological: Placebo booster; Placebo (single dose)
Experimental: Study Group 1, Older Adult Participants; Participants will receive one dose of ARCT-021 on Day 0, one dose of Placebo (saline) on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo	Biological: ARCT-021 single dose priming; ARCT-021 higher dose (one dose) + placebo (one dose); Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster
Experimental: Study Group 2, Older Adult Participants; Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo	Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster; Biological: ARCT-021 two lower dose priming; ARCT-021 lower dose (two doses, Day 0 and Day 28)
Experimental: Study Group 3, Older Adult Participants; Participants will receive one dose of ARCT-021 on Day 0, a second dose of ARCT-021 on Day 28 and on Day 208 either one dose of ARCT-021 or one dose of placebo	Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster; Biological: ARCT-021 two higher dose priming; ARCT-021 higher dose (two doses, Day 0 and Day 28)
Placebo Comparator: Study Group 4, Older Adult Participants; Participants will receive one dose of Placebo (saline) on Day 0, a second dose of Placebo on Day 28 and a third dose of Placebo on Day 208	Biological: Placebo (two doses), priming; Placebo (two doses, Day 0 and Day 28); Biological: Placebo booster; Placebo (single dose)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of participants reporting solicited local adverse events	Adverse events reported daily in a diary that reflect common symptoms or findings at the injection site following vaccination	for 7 days following each dose administration
Percentages of participants reporting solicited systemic adverse events	Adverse events reported daily in a diary that reflect generalized symptoms following vaccination	for 7 days following each dose administration
Percentages of participants reporting adverse events	spontaneously reported adverse events	28 days following each dose administration
Percentages of participants reporting serious adverse events	unsolicited adverse events that meet the definition of serious	Day 0 to Day 388
Percentages of participants reporting medically attended adverse events	unsolicited adverse events that lead to healthcare provider visit	Day 0 to Day 388
Percentages of participants reporting new onset of chronic disease	unsolicited adverse events associated with new diagnosis of chronic disease	Day 0 to Day 388
Percentages of participants with abnormal chemistry and hematology values	chemistry and hematology	Day 0 to Day 215
SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs	neutralizing antibody response	Day 0 to Day 388
Changes in SARS-CoV-2 serum neutralizing titers from before vaccination to each subsequent time point, expressed as GMFRs	neutralizing antibody response	Through Day 388
Percentages of participants achieving greater than or equal to 2-fold and 4-fold rises from before vaccination in SARS-CoV-2 serum neutralizing antibody levels	neutralizing antibody response	Through Day 388

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SARS-CoV-2 anti-S1, anti-RBD, and anti-N binding antibody levels, expressed as GMCs	SARS-CoV-2 anti S1, RBD, N binding antibody responses	Day 0 to Day 388
Changes in SARS-CoV-2 anti-S1, anti-RBD, and anti-N binding antibody levels from before vaccination to each subsequent time point, expressed as GMFRs	SARS-CoV-2 anti S1, RBD, N binding antibody responses	Through Day 388
Percentages of participants achieving greater than or equal to 2-fold and 4-fold rises from before vaccination in SARS-CoV-2 SARS-CoV-2 anti-S1, anti-RBD, and anti-N binding antibody levels	SARS-CoV-2 anti S1, RBD, N binding antibody responses	Through Day 388

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2021
• Primary Completion (Actual): March 1, 2022
• Study Completion (Actual): March 1, 2022

Study Registration Dates

• First Submitted: November 25, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): July 8, 2022
• Last Update Submitted That Met QC Criteria: July 7, 2022
• Last Verified: July 1, 2022

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
• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; Severe Acute Respiratory Syndrome; COVID-19; Coronavirus Infections; Infections; Communicable Diseases
• Other Study ID Numbers: ARCT-021-04

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
• product manufactured in and exported from the U.S.: No