Ascending Dose Study of Investigational SARS-CoV-2 Vaccine ARCT-021 in Healthy Adult Subjects

A Phase 1/2 Randomised, Double Blinded, Placebo Controlled, Ascending Dose Study to Assess the Safety, Tolerability, and Immunogenicity of ARCT-021 in Healthy Adult Subjects

Determine safety and tolerability and immungenicity of investigational vaccine ARCT-021 in healthy adult volunteers.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2
• Intervention / Treatment: Biological: ARCT-021 Dose 1; Other: Placebo; Biological: ARCT-021 Dose 2; Biological: ARCT-021 Dose 3; Biological: ARCT-021 Dose 4; Biological: ARCT-021 Dose Regimen 1; Biological: ARCT-021 Dose Regimen 2

Detailed Description

Randomized, double blinded (study site staff, subjects and Sponsor), placebo controlled, adaptive, ascending dose study evaluating administration of ARCT-021 in healthy adult subjects. 0.9% sterile saline will serve as a placebo control. Study drug (ARCT-021 or control) will be administered as an intramuscular (IM) injection. The study comprises two parts. In the Phase 1 part escalating dose levels given as a single injection to younger adults (21 to 55 years) will be evaluated sequentially. Two dose levels will be further evaluated in the Phase 2 part of the study in two expansion cohorts in younger adults (21 to 55 years) and in two elderly subject (56 to 80 years) cohorts.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • SingHealth Investigational Medicine Unit (IMU), Singapore General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy males or females aged 21 to 80 at the time of informed consent.
2. Body Mass Index 18-35 kg/m2, inclusive, at screening
3. Willing to refrain from strenuous exercise/activity (for example heavy lifting, weight training, intense aerobics classes etc.) and alcohol for at least 72 hours prior to study visits
4. Temperature is less than 99.3 degrees Fahrenheit (37.4 degrees Celsius) at screening AND at the pre-dose evaluation on Day 1
5. Willing and able to comply with protocol-defined procedures and complete all study visits
6. Males must be surgically sterile or willing to use adequate contraception; females must be post-menopausal, surgically sterile or willing to use adequate contraception

Exclusion Criteria:

1. Pregnant or breast feeding
2. Clinically significant abnormalities in medical history
3. Out of range screening laboratory results
4. Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B
5. Uncontrolled hypertension (BP > 160/100 mm Hg)
6. Uncontrolled diabetes
7. Any history of autoimmune disease
8. Immunodeficiency of any cause
9. History of Chronic liver disease
10. Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational drug, whichever is longer
11. Recent (within 1 year) history of, or current drug or alcohol abuse
12. Has any blood dyscrasias or significant disorder of coagulation
13. Has an acute illness, as determined by the investigator, with or without fever [temperature >38.0 degrees Celsius (100.4 degrees Fahrenheit)] within 72 hours prior to each vaccination
14. Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated.
15. Received or plans to receive another vaccine within 4 weeks before study vaccination or at any time during the study.
16. Receipt of any other SARS CoV-2 or other experimental coronavirus vaccine at any time prior to study or planned during the study
17. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Escalation Cohort dose 1 of ARCT-021, 21 - 55 years; Escalation Cohort dose 1 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle.	Biological: ARCT-021 Dose 1; ARCT-021 Dose 1 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP); Other: Placebo; Sterile 0.9% saline
Experimental: Escalation Cohort dose 2 of ARCT-021, 21 -55 years; Escalation Cohort dose 2 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose 2; ARCT-021 Dose 2 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021
Experimental: Escalation Cohort dose 3 of ARCT-021, 21 - 55 years; Escalation Cohort dose 3 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose 3; ARCT-021 Dose 3 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021
Experimental: Escalation Cohort dose 4 of ARCT-021, 21 - 55 years; Escalation Cohort dose 4 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose 4; ARCT-021 Dose 4 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021
Experimental: Expansion cohort dose regimen 1, 21 - 55 years.; Expansion cohort dose regimen 1, administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose Regimen 1; ARCT-021 dose regimen 1 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021
Experimental: Expansion cohort dose regimen 2, 21 - 55 years.; Expansion cohort dose regimen 2, administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose Regimen 2; ARCT-021 dose regimen 2 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021
Experimental: Expansion cohort dose regimen 1, 56 - 80 years; Expansion cohort dose regimen 1, administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose Regimen 1; ARCT-021 dose regimen 1 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021
Experimental: Expansion cohort dose regimen 2, 56 - 80 years; Expansion cohort dose regimen 2, administered through 0.5 mL intramuscular injection in the deltoid muscle.	Other: Placebo; Sterile 0.9% saline; Biological: ARCT-021 Dose Regimen 2; ARCT-021 dose regimen 2 is an investigational vaccine comprising a self-replicating (replicon) mRNA that encodes for the full length spike protein of 2019-nCoV formulated in a lipid nanoparticle (LNP): ARCT-021

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and dose-relationship of AEs	Safety and tolerability of ARCT-021 assessed by determining the incidence, severity and dose-relationship of AEs by dose	56 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric mean titre for SARS-CoV-2-specific serum neutralizing antibody	SARS-CoV-2-specific serum neutralizing antibody levels, expressed as GMT	Up to 56 days
Mean titre for SARS-CoV-2-specific serum neutralizing antibody levels	SARS-CoV-2-specific serum neutralizing antibody levels, expressed as mean titer	Up to 56 days
Geometric mean fold rise in titre for SARS-CoV-2-spike protein specific neutralizing antibody levels	GMFR in titre for SARS-CoV-2-spike protein specific neutralizing antibodies from before vaccination to each subsequent time point	Up to 56 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Increase in SARS-CoV-2--spike protein-specific binding antibody levels	GMFR in SARS-CoV-2--spike protein-specific binding antibody levels from before vaccination to each subsequent time point	Up to 56 days
Geometric mean SARS-CoV-2--spike protein-specific binding antibody titre	GMT for SARS-CoV-2--spike protein-specific binding antibody levels	Up to 56 days
Mean SARS-CoV-2--spike protein-specific binding antibody titre	Mean titer for SARS-CoV-2--spike protein-specific binding antibody levels	Up to 56 days
SARS-CoV-2-specific serum neutralizing antibody seroconversion rate	Proportion of participants that are seronegative before vaccination achieving a titer of greater than or equal to 20 for SARS-CoV-2-specific serum neutralizing antibodies	56 days
SARS-CoV-2-specific serum neutralizing antibody seroconversion rate (seropositive baseline)	Proportion of participants that are seropositive before vaccination achieving a greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2-specific serum neutralizing antibody levels	56 days

Collaborators and Investigators

• Sponsor: Arcturus Therapeutics, Inc.
• Investigators: Principal Investigator: Jenny Low Guek Hong, MD, SingHealth Investigational Medicine Unit (IMU)

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): January 29, 2021
• Study Completion (Actual): January 29, 2021

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: August 12, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: ARCT-021-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No