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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Covid19, SARS-CoV Infection, Corona Virus Infection

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who: are able to provide consent agree to comply with all study visits and procedures are willing and able to adhere to study restrictions are sexually active and willing to adhere to contraceptive requirements are male or female ≥18 or (in Singapore) ≥21 years of age are medically stable Exclusion Criteria: Individuals who: have had SARS-CoV-2 infection or COVID-19 disease. have had cancer except for cancers that were treated and that have low risk of returning have chronic kidney disease have some chronic lung diseases have some heart conditions have compromised immune systems are obese have sickle cell disease or some other blood disorders are current smokers and/or use illegal drugs have Type 2 diabetics are immunocompromised, immunodeficient or have had a transplant have autoimmune disease have other severe or uncontrolled diseases or disease that may interfere with the interpretation of the study have a positive test for hepatitis B or C or human immunodeficiency virus have had a severe reaction to previous investigational vaccines have a fever or are feeling sick close to the time of the first vaccination of the study have positive drug test at screening are pregnant are breastfeeding have a bleeding disorder have previously received an investigational coronavirus vaccine (SARS-CoV(1) or MERS) or who plan to be in other COVID-19 studies have recently been vaccinated with other vaccines have recently received blood products 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 other restrictions may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: sequential assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Group 1, Younger Adult Participants<br>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<br>* ARCT-021 higher dose (one dose) + placebo (one dose)<br>Biological: Randomized booster<br>* ARCT-021 (single dose) OR placebo, booster<br>|
| Experimental: Study Group 2, Younger Adult Participants<br>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<br>* ARCT-021 lower dose (two doses, Day 0 and Day 28)<br>Biological: Randomized booster<br>* ARCT-021 (single dose) OR placebo, booster<br>|
| Experimental: Study Group 3, Younger Adult Participants<br>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<br>* ARCT-021 higher dose (two doses, Day 0 and Day 28)<br>Biological: Randomized booster<br>* ARCT-021 (single dose) OR placebo, booster<br>|
| Placebo Comparator: Study Group 4, Younger Adult Participants<br>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<br>* Placebo (two doses, Day 0 and Day 28)<br>Biological: Placebo booster<br>* Placebo (single dose)<br>|
| Experimental: Study Group 1, Older Adult Participants<br>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<br>* ARCT-021 higher dose (one dose) + placebo (one dose)<br>Biological: Randomized booster<br>* ARCT-021 (single dose) OR placebo, booster<br>|
| Experimental: Study Group 2, Older Adult Participants<br>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<br>* ARCT-021 lower dose (two doses, Day 0 and Day 28)<br>Biological: Randomized booster<br>* ARCT-021 (single dose) OR placebo, booster<br>|
| Experimental: Study Group 3, Older Adult Participants<br>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<br>* ARCT-021 higher dose (two doses, Day 0 and Day 28)<br>Biological: Randomized booster<br>* ARCT-021 (single dose) OR placebo, booster<br>|
| Placebo Comparator: Study Group 4, Older Adult Participants<br>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<br>* Placebo (two doses, Day 0 and Day 28)<br>Biological: Placebo booster<br>* Placebo (single dose)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2 Vaccine, Coronavirus Virus Diseases, RNA COVID 19, COVID 19 Vaccine Arcturus, self amplifying RNA vaccine