Clinical trial NCT04668339: A Trial Evaluating the Safety and Effects of an RNA Vaccine ARCT-021 in Healthy Adults
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Covid19
SARS-CoV Infection
Corona Virus Infection
Keywords: SARS-CoV-2 Vaccine
Coronavirus Virus Diseases
RNA COVID 19
COVID 19 Vaccine Arcturus
self amplifying RNA vaccine
Lead sponsor: Arcturus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-16
Enrollment: 581
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: sequential assignment
Primary purpose: PREVENTION

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

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.

Eligibility 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

Primary outcomes:
measure: Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Each Priming Vaccination
timeFrame: For 7 days following each dose administration (Day 0 up to Day 7 for Vaccination 1 and Day 29 up to Day 35 for Vaccination 2)
measure: Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Booster Vaccination
timeFrame: For 7 days following each dose administration (Day 208 up to Day 215)
measure: Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Each Priming Vaccination
timeFrame: For 7 days following each dose administration (Day 0 up to Day 7 for Vaccination 1 and Day 29 up to Day 35 for Vaccination 2)
measure: Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Booster Vaccination
timeFrame: For 7 days post booster dose administration (Day 208 up to Day 215)
measure: Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Each Priming Vaccination
timeFrame: 28 days following each dose administration (Day 0 up to Day 28 for Vaccination 1 and Day 29 up to Day 56 for Vaccination 2)
measure: Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Booster Vaccination
timeFrame: 28 days following each dose administration (Day 208 up to 236 days)
measure: Percentage of Participants Reporting Treatment-Emergent Serious Adverse Events (SAE), Medically Attended Adverse Events (MAAE) and New Onset of Chronic Disease (NOCD) Post Each Priming Vaccination
timeFrame: Up to Day 207
measure: Percentage of Participants Reporting Treatment-emergent Serious Adverse Events, Medically Attended Adverse Events and New Onset of Chronic Disease Post Booster Vaccination
timeFrame: Day 208 to early termination (up to 396 days)
measure: Geometric Mean Titer (GMT) of Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies Post Priming Vaccination
timeFrame: Day 1
measure: GMT of SARS-CoV-2 Neutralizing Antibodies Post Priming Vaccination
timeFrame: Day 56
measure: GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination
timeFrame: Day 208
measure: GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination
timeFrame: Day 236
measure: Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Priming Vaccination
timeFrame: Day 56
measure: Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination
timeFrame: Day 208
measure: GMFR in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination
timeFrame: Day 236
measure: Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 56
timeFrame: Baseline up to Day 56
measure: Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 208
timeFrame: Baseline up to Day 208
measure: Percentages of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Serum Neutralizing Antibody Levels at Day 236
timeFrame: Baseline up to Day 236
Secondary outcomes:
measure: Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Priming Vaccination
timeFrame: Days 0 and 56
measure: Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Booster Vaccination
timeFrame: Day 208 and 236
measure: Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Before Vaccination to Day 56
timeFrame: Day 56
measure: Percentage of Participants Achieving Greater Than or Equal to 2-fold and 4-fold Increase From Before Vaccination (Baseline) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels
timeFrame: Day 56
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Arcturus Investigational Site 103
state: Arizona
city: Tucson
country: United States
facility: Arcturus Investigational Site 107
state: Arizona
city: San Diego
country: United States
facility: Arcturus Investigational Site 112
state: California
city: Melbourne
country: United States
facility: Arcturus Investigational Site 104
state: Florida
city: Orlando
country: United States
facility: Arcturus Investigational Site 105
state: Florida
city: Pinellas Park
country: United States
facility: Arcturus Investigational Site 106
state: Florida
city: The Villages
country: United States
facility: Arcturus Investigational Site 109
state: Florida
city: Peoria
country: United States
facility: Arcturus Investigational Site 101
state: Illinois
city: Rockville
country: United States
facility: Arcturus Investigational Site 110
state: Maryland
city: Anderson
country: United States
facility: Arcturus Investigational Site 102
state: South Carolina
city: Austin
country: United States
facility: Arcturus Investigational Site 111
state: Texas
city: Dallas
country: United States
facility: Arcturus Investigational Site 108
state: Texas
city: Singapore
country: Singapore
facility: Arcturus Investigational Site 204
city: Singapore
country: Singapore
facility: Arcturus Investigational Site 201
city: Singapore
country: Singapore
facility: Arcturus Investigational Site 203
Study officials:
References: