NCT04668339

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

Terminated Phase 2 Results posted Last updated 15 May 2025

What this trial tests

Phase 2 trial testing ARCT-021 single dose priming in Covid19 in 581 participants. Terminated before completion.

Timeline

7 January 2021

Primary endpoint
1 March 2022

1 March 2022

Quick facts

Lead sponsor	Arcturus Therapeutics, Inc.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	581
Start date	7 January 2021
Primary completion	1 March 2022
Estimated completion	1 March 2022
Sites	15 locations across Singapore, United States

Drugs / interventions tested

• ARCT-021 single dose priming — full drug profile →
• ARCT-021 two lower dose priming — full drug profile →
• ARCT-021 two higher dose priming
• Placebo (two doses), priming — full drug profile →
• Randomized booster — full drug profile →
• Placebo booster — full drug profile →

Conditions studied

• Covid19 — all drugs for Covid19 →
• SARS-CoV Infection — all drugs for SARS-CoV Infection →
• Corona Virus Infection — all drugs for Corona Virus Infection →

Sponsor

Arcturus Therapeutics, Inc. — full company profile →

Who can join

18 and older, any sex, with Covid19 or SARS-CoV Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Each Priming Vaccination Primary · 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.

Vaccination 1: Pain

Group	Value	95% CI
Treatment A	52.8
Treatment B	48.6
Treatment C	57.6
Treatment D	8.2

Vaccination 1: Erythema (Redness)

Group	Value	95% CI
Treatment A	14.8
Treatment B	19.7
Treatment C	11.1
Treatment D	7.5

Vaccination 1: Swelling (Hardness)

Group	Value	95% CI
Treatment A	11.3
Treatment B	15.5
Treatment C	9.0
Treatment D	5.5

Vaccination 1: Injection Site Tenderness

Group	Value	95% CI
Treatment A	79.6
Treatment B	75.4
Treatment C	83.3
Treatment D	19.9

Vaccination 2: Pain

Group	Value	95% CI
Treatment A	7.9
Treatment B	33.1
Treatment C	44.5
Treatment D	5.9

Vaccination 2: Erythema (Redness)

Group	Value	95% CI
Treatment A	7.1
Treatment B	14.6
Treatment C	8.0
Treatment D	8.9

Vaccination 2: Swelling (Hardness)

Group	Value	95% CI
Treatment A	4.7
Treatment B	11.5
Treatment C	4.4
Treatment D	3.0

Vaccination 2: Injection Site Tenderness

Group	Value	95% CI
Treatment A	15.0
Treatment B	67.7
Treatment C	75.2
Treatment D	15.6

Percentage of Participants Reporting Solicited Local Adverse Events Within 7 Days Post Booster Vaccination Primary · 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.

Pain

Group	Value	95% CI
Treatment E1	51.2
Treatment F1	36.8
Treatment G1	39.5
Treatment H1	5.1

Erythema (Redness)

Group	Value	95% CI
Treatment E1	9.3
Treatment F1	7.9
Treatment G1	7.9
Treatment H1	2.6

Swelling (Hardness)

Group	Value	95% CI
Treatment E1	11.6
Treatment F1	5.3
Treatment G1	7.9
Treatment H1	0

Injection Site Tenderness

Group	Value	95% CI
Treatment E1	81.4
Treatment F1	65.8
Treatment G1	73.7
Treatment H1	12.8

Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Each Priming Vaccination Primary · 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.

Vaccination 1: Fever

Group	Value	95% CI
Treatment A	4.2
Treatment B	2.1
Treatment C	2.8
Treatment D	0

Vaccination 1: Headache

Group	Value	95% CI
Treatment A	43.0
Treatment B	34.5
Treatment C	39.6
Treatment D	19.2

Vaccination 1: Fatigue

Group	Value	95% CI
Treatment A	47.2
Treatment B	36.6
Treatment C	40.3
Treatment D	20.5

Vaccination 1: Myalgia

Group	Value	95% CI
Treatment A	44.4
Treatment B	28.9
Treatment C	39.6
Treatment D	8.2

Vaccination 1: Arthralgia

Group	Value	95% CI
Treatment A	21.1
Treatment B	15.5
Treatment C	17.4
Treatment D	8.2

Vaccination 1: Nausea

Group	Value	95% CI
Treatment A	10.6
Treatment B	8.5
Treatment C	6.3
Treatment D	7.5

Vaccination 1: Chills

Group	Value	95% CI
Treatment A	28.9
Treatment B	16.9
Treatment C	22.9
Treatment D	2.1

Vaccination 1: Diarrhea

Group	Value	95% CI
Treatment A	12.0
Treatment B	12.7
Treatment C	16.0
Treatment D	9.6

Percentage of Participants Reporting Solicited Systemic Adverse Events Within 7 Days Post Booster Vaccination Primary · 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.

Fever

Group	Value	95% CI
Treatment E1	11.6
Treatment F1	0
Treatment G1	5.3
Treatment H1	2.6

Headache

Group	Value	95% CI
Treatment E1	60.5
Treatment F1	34.2
Treatment G1	31.6
Treatment H1	25.6

Fatigue

Group	Value	95% CI
Treatment E1	69.8
Treatment F1	34.2
Treatment G1	50.0
Treatment H1	25.6

Myalgia

Group	Value	95% CI
Treatment E1	62.8
Treatment F1	31.6
Treatment G1	42.1
Treatment H1	12.8

Arthralgia

Group	Value	95% CI
Treatment E1	48.8
Treatment F1	21.1
Treatment G1	31.6
Treatment H1	12.8

Nausea

Group	Value	95% CI
Treatment E1	27.9
Treatment F1	7.9
Treatment G1	10.5
Treatment H1	2.6

Chills

Group	Value	95% CI
Treatment E1	44.2
Treatment F1	18.4
Treatment G1	21.1
Treatment H1	7.7

Diarrhea

Group	Value	95% CI
Treatment E1	25.6
Treatment F1	18.4
Treatment G1	10.5
Treatment H1	10.3

Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Each Priming Vaccination Primary · 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.

Vaccination 1

Group	Value	95% CI
Treatment A	20.7
Treatment B	22.2
Treatment C	17.9
Treatment D	19.2

Vaccination 2

Group	Value	95% CI
Treatment A	19.1
Treatment B	19.4
Treatment C	8.6
Treatment D	20.7

Percentage of Participants Reporting Unsolicited Adverse Events Up to 28 Days Post Booster Vaccination Primary · 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.

Group	Value	95% CI
Treatment E1	15.9
Treatment F1	14.6
Treatment G1	11.9
Treatment H1	9.1

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 Primary · 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

Any SAEs

Group	Value	95% CI
Treatment A	0
Treatment B	2.1
Treatment C	0.7
Treatment D	2.1

Any MAAEs

Group	Value	95% CI
Treatment A	16.6
Treatment B	20.8
Treatment C	18.6
Treatment D	17.1

Any NOCDs

Group	Value	95% CI
Treatment A	4.1
Treatment B	7.6
Treatment C	2.8
Treatment D	2.7

Percentage of Participants Reporting Treatment-emergent Serious Adverse Events, Medically Attended Adverse Events and New Onset of Chronic Disease Post Booster Vaccination Primary · 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

Any SAEs

Group	Value	95% CI
Treatment E1	0
Treatment F1	0
Treatment G1	2.4
Treatment H1	0

Any MAAEs

Group	Value	95% CI
Treatment E1	11.4
Treatment F1	19.5
Treatment G1	11.9
Treatment H1	12.1

Any NOCDs

Group	Value	95% CI
Treatment E1	2.3
Treatment F1	4.9
Treatment G1	0
Treatment H1	0

Geometric Mean Titer (GMT) of Serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibodies Post Priming Vaccination Primary · Day 1

Group	Value	95% CI
Treatment A	4.40	4.03 – 4.80
Treatment B	5.14	4.47 – 5.90
Treatment C	5.31	4.57 – 6.18
Treatment D	4.75	4.30 – 5.25

GMT of SARS-CoV-2 Neutralizing Antibodies Post Priming Vaccination Primary · Day 56

Group	Value	95% CI
Treatment A	5.47	4.61 – 6.48
Treatment B	13.37	10.65 – 16.79
Treatment C	15.31	11.89 – 19.72
Treatment D	4.21	3.89 – 4.57

GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination Primary · Day 208

Group	Value	95% CI
Treatment E1	13.37	7.84 – 22.80
Treatment F1	20.71	10.47 – 40.97
Treatment G1	14.04	7.14 – 27.62
Treatment H1	11.84	7.57 – 18.51

GMT of SARS-CoV-2 Neutralizing Antibodies Post Booster Vaccination Primary · Day 236

Group	Value	95% CI
Treatment E1	229.70	135.70 – 388.80
Treatment F1	503.18	296.57 – 853.72
Treatment G1	380.77	249.24 – 581.71
Treatment H1	10.73	6.56 – 17.56

Adverse events — posted to ClinicalTrials.gov

Time frame: Vaccination 1 and 2: Day 1 up to Day 207; Booster Vaccination: Day 208 to early termination (up to 396 days). Groups E-H1 also include participants who did not receive booster dose. As pre-specified, if a participant didn't receive booster dose but had safety data collected for the booster vaccination period, the participant was included in the placebo booster group for summarization (Group H1).. Reporting threshold: 2.5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment A

Serious: 0/145 (0%)

Deaths: 0/145

Treatment B

Serious: 3/144 (2%)

Deaths: 0/144

Treatment C

Serious: 1/145 (1%)

Deaths: 0/145

Treatment D

Serious: 3/146 (2%)

Deaths: 0/146

Treatment E1

Serious: 0/44 (0%)

Deaths: 0/44

Treatment F1

Serious: 0/41 (0%)

Deaths: 0/41

Treatment G1

Serious: 1/42 (2%)

Deaths: 0/42

Treatment H1

Serious: 0/99 (0%)

Deaths: 0/99

Treatment A - Reactogenicity Analysis

Serious: 0/142 (0%)

Deaths: 0/142

Treatment B - Reactogenicity Analysis

Serious: 0/142 (0%)

Deaths: 0/142

Treatment C - Reactogenicity Analysis

Serious: 0/144 (0%)

Deaths: 0/144

Treatment D - Reactogenicity Analysis

Serious: 0/146 (0%)

Deaths: 0/146

Treatment E1 - Reactogenicity Analysis

Serious: 0/43 (0%)

Deaths: 0/43

Treatment F1- Reactogenicity Analysis

Serious: 0/38 (0%)

Deaths: 0/38

Treatment G1 - Reactogenicity Analysis

Serious: 0/38 (0%)

Deaths: 0/38

Treatment H1 - Reactogenicity Analysis

Serious: 0/39 (0%)

Deaths: 0/39

Serious adverse events (10 terms)

Reaction	System	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E1	Treatment F1	Treatment G1	Treatment H1	Treatment A - Reactogenici…	Treatment B - Reactogenici…	Treatment C - Reactogenici…	Treatment D - Reactogenici…	Treatment E1 - Reactogenic…	Treatment F1- Reactogenici…	Treatment G1 - Reactogenic…	Treatment H1 - Reactogenic…
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Cholecystitis	Hepatobiliary disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Accidental overdose	Injury, poisoning and procedural complications	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Drug abuse	Psychiatric disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Pulmonary venous thrombosis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Other adverse events (54 terms — click to expand)

Reaction	System	Treatment A	Treatment B	Treatment C	Treatment D	Treatment E1	Treatment F1	Treatment G1	Treatment H1	Treatment A - Reactogenici…	Treatment B - Reactogenici…	Treatment C - Reactogenici…	Treatment D - Reactogenici…	Treatment E1 - Reactogenic…	Treatment F1- Reactogenici…	Treatment G1 - Reactogenic…	Treatment H1 - Reactogenic…
Injection site tenderness	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site tenderness	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site tenderness	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Erythema	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Swelling	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Pain	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Erythema	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Chills	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Injection site Swelling	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—
Fever	General disorders	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—	—

Most-reported serious reactions: Atrial fibrillation, Small intestinal obstruction, Cholecystitis, Accidental overdose, Chronic lymphocytic leukaemia, Ischaemic stroke, Drug abuse, Pulmonary venous thrombosis.

Data from ClinicalTrials.gov NCT04668339 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. mRNA vaccines for infectious diseases: principles, delivery and clinical translation.
   Chaudhary N, Weissman D, Whitehead KA. · · 2021 · cited 1014× · PMID 34433919 · DOI 10.1038/s41573-021-00283-5
2. Advances in COVID-19 mRNA vaccine development.
   Fang E, Liu X, Li M, Zhang Z, et al · · 2022 · cited 368× · PMID 35322018 · DOI 10.1038/s41392-022-00950-y
3. COVID-19 vaccines: rapid development, implications, challenges and future prospects.
   Kashte S, Gulbake A, El-Amin Iii SF, Gupta A. · · 2021 · cited 240× · PMID 33677814 · DOI 10.1007/s13577-021-00512-4
4. Efficacy and safety of COVID-19 vaccines.
   Graña C, Ghosn L, Evrenoglou T, Jarde A, et al · · 2022 · cited 227× · PMID 36473651 · DOI 10.1002/14651858.cd015477
5. mRNA vaccines for COVID-19: what, why and how.
   Park JW, Lagniton PNP, Liu Y, Xu RH. · · 2021 · cited 212× · PMID 33907508 · DOI 10.7150/ijbs.59233
6. Nanoparticles in the clinic: An update post COVID-19 vaccines.
   Anselmo AC, Mitragotri S. · · 2021 · cited 211× · PMID 34514159 · DOI 10.1002/btm2.10246
7. From influenza to COVID-19: Lipid nanoparticle mRNA vaccines at the frontiers of infectious diseases.
   Pilkington EH, Suys EJA, Trevaskis NL, Wheatley AK, et al · · 2021 · cited 192× · PMID 34153512 · DOI 10.1016/j.actbio.2021.06.023
8. Recent Advancement in mRNA Vaccine Development and Applications.
   Al Fayez N, Nassar MS, Alshehri AA, Alnefaie MK, et al · · 2023 · cited 95× · PMID 37514158 · DOI 10.3390/pharmaceutics15071972