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

Phase 2

Terminated

Conditions: SARS-CoV Infection
Corona Virus Infection
Covid19

Interventions: Biological: ARCT-021 two lower dose priming
Biological: ARCT-021 single dose priming
Biological: ARCT-021 two higher dose priming
Biological: Placebo (two doses), priming
Biological: Randomized booster
Biological: Placebo booster

Registration Number: NCT04668339

Lead Sponsor: Arcturus Therapeutics, Inc.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 581

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Group 2, Younger Adult Participants	ARCT-021 two lower dose priming	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
Study Group 2, Younger Adult Participants	Randomized booster	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
Study Group 3, Younger Adult Participants	Randomized booster	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
Study Group 1, Older Adult Participants	ARCT-021 single dose priming	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
Study Group 2, Older Adult Participants	ARCT-021 two lower dose priming	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
Study Group 2, Older Adult Participants	Randomized booster	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
Study Group 3, Older Adult Participants	ARCT-021 two higher dose priming	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
Study Group 3, Older Adult Participants	Randomized booster	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
Study Group 4, Older Adult Participants	Placebo (two doses), priming	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
Study Group 4, Younger Adult Participants	Placebo booster	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
Study Group 1, Younger Adult Participants	Randomized booster	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
Study Group 1, Older Adult Participants	Randomized booster	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
Study Group 1, Younger Adult Participants	ARCT-021 single dose priming	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
Study Group 4, Older Adult Participants	Placebo booster	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
Study Group 4, Younger Adult Participants	Placebo (two doses), priming	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
Study Group 3, Younger Adult Participants	ARCT-021 two higher dose priming	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

Primary Outcome Measures

Name	Time	Method
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	Baseline up to Day 56
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	Baseline up to Day 236
GMFR in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination	Day 236	GMFR is reported as a ratio to baseline (Day 0).
Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Each Priming Vaccination	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)	Per prespecified analysis, solicited local adverse events were defined as pain, erythema, swelling, or injection site tenderness. Solicited adverse reactions were recorded by the participant in an eDiary. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Booster Vaccination	For 7 days following each dose administration (Day 208 up to Day 215)	Per prespecified analysis, solicited local adverse events were defined as pain, erythema, swelling, or injection site tenderness. Solicited adverse reactions were recorded by the participant in an eDiary. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Each Priming Vaccination	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)	Per prespecified analysis, solicited systemic adverse events were defined as fever, headache, fatigue, myalgia, arthralgia, nausea, chills, diarrhea, dizziness, and vomiting. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Booster Vaccination	For 7 days post booster dose administration (Day 208 up to Day 215)	Per prespecified analysis, solicited systemic adverse events were defined as fever, headache, fatigue, myalgia, arthralgia, nausea, chills, diarrhea, dizziness, and vomiting. Per prespecified analysis, solicited adverse events were not evaluated for severity (such as, serious or non-serious). A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Each Priming Vaccination	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)	An unsolicited AE was defined as any AE (serious and nonserious) occurring after administration of first dose of study vaccine and before the end of study. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Booster Vaccination	28 days following each dose administration (Day 208 up to 236 days)	An unsolicited AE was defined as any AE (serious and nonserious) occurring after administration of first dose of study vaccine and before the end of study. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
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	Up to Day 207	SAEs were defined as any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, resulted in a congenital anomaly or birth defect, or was an important medical event. An NOCD was defined as any AE that led to the new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Percentage of Participants Reporting Treatment-emergent Serious Adverse Events, Medically Attended Adverse Events and New Onset of Chronic Disease Post Booster Vaccination	Day 208 to early termination (up to 396 days)	SAEs were defined as any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, resulted in a congenital anomaly or birth defect, or was an important medical event. An NOCD was defined as an AE that led to the new diagnosis of a chronic medical condition that was not present or suspected prior to enrollment. An MAAE was an AE that led to an unscheduled visit (including a telemedicine visit) to a healthcare practitioner. A summary of all unsolicited adverse events and solicited adverse events regardless of causality is located in the Reported Adverse Events module.
Geometric Mean Titer (GMT) of Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies Post Priming Vaccination	Day 1
GMT of SARS-CoV-2 Neutralizing Antibodies Post Priming Vaccination	Day 56
GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination	Day 236
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Priming Vaccination	Day 56	GMFR is reported as a ratio to baseline (Day 0).
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Neutralizing Antibody Titers Post Booster Vaccination	Day 208	GMFR is reported as a ratio to baseline (Day 0).
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	Baseline up to Day 208

Secondary Outcome Measures

Name	Time	Method
Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Booster Vaccination	Day 208 and 236
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	Day 56
Geometric Mean Concentration of SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Post Priming Vaccination	Days 0 and 56
Geometric Mean Fold Rise (GMFR) in SARS-CoV-2 Anti-S1, Anti-RBD, and Anti-N Binding Antibody Levels Before Vaccination to Day 56	Day 56

Trial Locations

Locations (15): Arcturus Investigational Site 201
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Singapore, Singapore
Arcturus Investigational Site 107
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Tucson, Arizona, United States
Arcturus Investigational Site 112
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San Diego, California, United States
Arcturus Investigational Site 104
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Melbourne, Florida, United States
Arcturus Investigational Site 103
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Chandler, Arizona, United States
Arcturus Investigational Site 106
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Pinellas Park, Florida, United States
Arcturus Investigational Site 108
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Dallas, Texas, United States
Arcturus Investigational Site 105
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Orlando, Florida, United States
Arcturus Investigational Site 204
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Singapore, Singapore
Arcturus Investigational Site 109
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The Villages, Florida, United States
Arcturus Investigational Site 110
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Rockville, Maryland, United States
Arcturus Investigational Site 102
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Anderson, South Carolina, United States
Arcturus Investigational Site 203
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Singapore, Singapore
Arcturus Investigational Site 101
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Peoria, Illinois, United States
Arcturus Investigational Site 111
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Austin, Texas, United States