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

• ClinicalTrials.gov Identifier: NCT04668339
• Recruitment Status: Terminated
• First Posted: December 16, 2020
• Last Update Posted: July 8, 2022
• Sponsor: Arcturus Therapeutics, Inc.
• Information provided by (Responsible Party): Arcturus Therapeutics, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Covid19; SARS-CoV Infection; Corona Virus Infection	Biological: ARCT-021 single dose priming; Biological: ARCT-021 two lower dose priming; Biological: ARCT-021 two higher dose priming; Biological: Placebo (two doses), priming; Biological: Randomized booster; Biological: Placebo booster	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 581 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: sequential assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Observer blind
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: January 7, 2021
• Actual Primary Completion Date: March 1, 2022
• Actual Study Completion Date: March 1, 2022

Arms and Interventions

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: ARCT-021 two lower dose priming; ARCT-021 lower dose (two doses, Day 0 and Day 28); Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster
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: ARCT-021 two higher dose priming; ARCT-021 higher dose (two doses, Day 0 and Day 28); Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster
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: ARCT-021 two lower dose priming; ARCT-021 lower dose (two doses, Day 0 and Day 28); Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster
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: ARCT-021 two higher dose priming; ARCT-021 higher dose (two doses, Day 0 and Day 28); Biological: Randomized booster; ARCT-021 (single dose) OR placebo, booster
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)

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. SARS-CoV-2 anti-S1, anti-RBD, and anti-N binding antibody levels, expressed as GMCs [ Time Frame: Day 0 to Day 388 ]
   SARS-CoV-2 anti S1, RBD, N binding antibody responses
2. 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 [ Time Frame: Through Day 388 ]
   SARS-CoV-2 anti S1, RBD, N binding antibody responses
3. 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 [ Time Frame: Through Day 388 ]
   SARS-CoV-2 anti S1, RBD, N binding antibody responses

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Arcturus Investigational Site 103

Chandler, Arizona, United States, 85224

Arcturus Investigational Site 107

Tucson, Arizona, United States, 85741

United States, California

Arcturus Investigational Site 112

San Diego, California, United States, 92108

United States, Florida

Arcturus Investigational Site 104

Melbourne, Florida, United States, 32934

Arcturus Investigational Site 105

Orlando, Florida, United States, 32806

Arcturus Investigational Site 106

Pinellas Park, Florida, United States, 33781

Arcturus Investigational Site 109

The Villages, Florida, United States, 32162

United States, Illinois

Arcturus Investigational Site 101

Peoria, Illinois, United States, 61614

United States, Maryland

Arcturus Investigational Site 110

Rockville, Maryland, United States, 20850

United States, South Carolina

Arcturus Investigational Site 102

Anderson, South Carolina, United States, 29621

United States, Texas

Arcturus Investigational Site 111

Austin, Texas, United States, 78705

Arcturus Investigational Site 108

Dallas, Texas, United States, 75234

Singapore

Arcturus Investigational Site 204

Singapore, Singapore, 117599

Arcturus Investigational Site 201

Singapore, Singapore, 169608

Arcturus Investigational Site 203

Singapore, Singapore, 308433

Sponsors and Collaborators

Arcturus Therapeutics, Inc.

More Information

• Responsible Party: Arcturus Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04668339
• Other Study ID Numbers: ARCT-021-04
• First Posted: December 16, 2020
• Last Update Posted: July 8, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual participant data will only be made available to study investigators at this time.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Arcturus Therapeutics, Inc.:

SARS-CoV-2 Vaccine; Coronavirus Virus Diseases; RNA COVID 19; COVID 19 Vaccine Arcturus; self amplifying RNA vaccine

Additional relevant MeSH terms:

COVID-19; Infections; Communicable Diseases; Coronavirus Infections; Severe Acute Respiratory Syndrome; Disease Attributes; Pathologic Processes; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases