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.

Study Timeline

• Study Start: 2021-08-30
• Study First Submitted: 2021-08-30
• Study First Submitted QC: 2021-09-03
• Study First Posted: 2021-09-08
• Primary Completion: 2023-12-19
• Study Completion: 2023-12-19
• Disposition First Posted: 2024-07-30
• Status Verified: 2024-11
• Disposition First Submitted: 2024-12-16
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

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

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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

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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 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 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 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 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 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 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
Percentage of participants reporting solicited local or systemic adverse events	For 7 days following each study vaccination	Solicited adverse events reported daily in a diary that reflect generalized symptoms or findings at the injection site following each vaccination
Percentage of participants reporting medically attended adverse events	Through Final Visit (365 days after last study vaccine dose)	Medically attended adverse event is an AE that leads to an unscheduled visit with a health care provider
Percentage of participants reporting serious adverse events	Through Final Visit (365 days after last study vaccine dose)	Unsolicited adverse events that meet the definition of serious
SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs	Through Final Visit (365 days after last study vaccine dose)	Neutralizing antibody response
Percentages of participants achieving greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels	Through Final Visit (365 days after last study vaccine dose)	Neutralizing antibody response
SARS-CoV-2 full-length spike, RBD, and N binding antibody levels, expressed as GMCs	Through Final Visit (365 days after last study vaccine dose)	Binding antibody response
Percentage of participants reporting unsolicited adverse events	For 28 days following each study vaccination	Spontaneously reported adverse events
Percentage of participants reporting adverse events leading to discontinuation from study vaccine/study withdrawal	Through Final Visit (365 days after last study vaccine dose)	Unsolicited adverse events that meet stopping rules
Changes in SARS-CoV-2 serum neutralizing levels from before vaccination to each subsequent time point, expressed as GMFRs	Through Final Visit (365 days after last study vaccine dose)	Neutralizing antibody response
Percentages of participants achieving greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 full-length spike, RBD, and N binding antibody levels	Through Final Visit (365 days after last study vaccine dose)	Binding antibody response
GMC ratio (ARCT-021/ARCT-165, ARCT-165/ARCT-154, and ARCT-021/ARCT-154)	Through Final Visit (365 days after last study vaccine dose)	Neutralizing antibody response
Changes in SARS-CoV-2 full-length spike, RBD, and N binding antibody levels from before vaccination to each subsequent time point, expressed as GMFRs	Through Final Visit (365 days after last study vaccine dose)	Binding antibody response

Trial Locations

Locations (4)

Arcturus Investigational Site 101; 🇸🇬 Singapore, Singapore

Arcturus Investigational Site 202; 🇺🇸 Wichita, Kansas, United States

Arcturus Investigational Site 301; 🇿🇦 Diepkloof, Soweto, South Africa

Arcturus Investigational Site 201; 🇺🇸 Kansas City, Missouri, United States