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

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

Detailed Description
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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.

Official Title
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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

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: ARCT-021 Dose 1
* 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
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females aged 21 to 80 at the time of informed consent. Body Mass Index 18-35 kg/m2, inclusive, at screening 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 Temperature is less than 99.3 degrees Fahrenheit (37.4 degrees Celsius) at screening AND at the pre-dose evaluation on Day 1 Willing and able to comply with protocol-defined procedures and complete all study visits 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: Pregnant or breast feeding Clinically significant abnormalities in medical history Out of range screening laboratory results Known history of or positive test for human immunodeficiency virus (HIV), hepatitis C or chronic hepatitis B Uncontrolled hypertension (BP > 160/100 mm Hg) Uncontrolled diabetes Any history of autoimmune disease Immunodeficiency of any cause History of Chronic liver disease Treatment with another investigational drug, biological agent, or device within one month of screening, or 5 half-lives of investigational drug, whichever is longer Recent (within 1 year) history of, or current drug or alcohol abuse Has any blood dyscrasias or significant disorder of coagulation 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 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. Received or plans to receive another vaccine within 4 weeks before study vaccination or at any time during the study. Receipt of any other SARS CoV-2 or other experimental coronavirus vaccine at any time prior to study or planned during the study 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escalation Cohort dose 1 of ARCT-021, 21 - 55 years<br>Escalation Cohort dose 1 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose 1<br>* 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)<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Escalation Cohort dose 2 of ARCT-021, 21 -55 years<br>Escalation Cohort dose 2 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose 2<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Escalation Cohort dose 3 of ARCT-021, 21 - 55 years<br>Escalation Cohort dose 3 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose 3<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Escalation Cohort dose 4 of ARCT-021, 21 - 55 years<br>Escalation Cohort dose 4 of ARCT-021 administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose 4<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Expansion cohort dose regimen 1, 21 - 55 years.<br>Expansion cohort dose regimen 1, administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose Regimen 1<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Expansion cohort dose regimen 2, 21 - 55 years.<br>Expansion cohort dose regimen 2, administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose Regimen 2<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Expansion cohort dose regimen 1, 56 - 80 years<br>Expansion cohort dose regimen 1, administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose Regimen 1<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|
| Experimental: Expansion cohort dose regimen 2, 56 - 80 years<br>Expansion cohort dose regimen 2, administered through 0.5 mL intramuscular injection in the deltoid muscle. | Biological: ARCT-021 Dose Regimen 2<br>* 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<br>Other: Placebo<br>* Sterile 0.9% saline<br>|

What is the study measuring?
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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 |