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

Covid19 Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04668339
• Other study ID #: ARCT-021-04
• Status: Terminated
• Phase: Phase 2
• Start date: January 7, 2021
• Est. completion date: March 1, 2022

Study information

• Verified date: July 2022
• Source: Arcturus Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 581
• Est. completion date: March 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Corona Virus Infection
• Coronavirus Infections
• COVID-19
• Covid19
• Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

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

Locations

Country	Name	City	State
Singapore	Arcturus Investigational Site 201	Singapore
Singapore	Arcturus Investigational Site 203	Singapore
Singapore	Arcturus Investigational Site 204	Singapore
United States	Arcturus Investigational Site 102	Anderson	South Carolina
United States	Arcturus Investigational Site 111	Austin	Texas
United States	Arcturus Investigational Site 103	Chandler	Arizona
United States	Arcturus Investigational Site 108	Dallas	Texas
United States	Arcturus Investigational Site 104	Melbourne	Florida
United States	Arcturus Investigational Site 105	Orlando	Florida
United States	Arcturus Investigational Site 101	Peoria	Illinois
United States	Arcturus Investigational Site 106	Pinellas Park	Florida
United States	Arcturus Investigational Site 110	Rockville	Maryland
United States	Arcturus Investigational Site 112	San Diego	California
United States	Arcturus Investigational Site 109	The Villages	Florida
United States	Arcturus Investigational Site 107	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Arcturus Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Percentages of participants reporting adverse events	spontaneously reported adverse events	28 days following each dose administration
Primary	Percentages of participants reporting serious adverse events	unsolicited adverse events that meet the definition of serious	Day 0 to Day 388
Primary	Percentages of participants reporting medically attended adverse events	unsolicited adverse events that lead to healthcare provider visit	Day 0 to Day 388
Primary	Percentages of participants reporting new onset of chronic disease	unsolicited adverse events associated with new diagnosis of chronic disease	Day 0 to Day 388
Primary	Percentages of participants with abnormal chemistry and hematology values	chemistry and hematology	Day 0 to Day 215
Primary	SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs	neutralizing antibody response	Day 0 to Day 388
Primary	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
Primary	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	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
Secondary	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
Secondary	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