Clinical trial NCT05037097: A Trial Evaluating the Safety and Immunogenicity of 3 COVID-19 SARS-CoV-2 RNA Vaccines in Healthy Adults
Official title: A Phase 1/2 Randomized, Observer-Blind Study of the Safety, Reactogenicity, and Immunogenicity of 3 SARS-CoV-2 RNA Vaccine Candidates in Adults Previously Vaccinated and Not Previously Vaccinated Against SARS-CoV-2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: COVID-19
SARS-CoV-2 Infection
Corona Virus Infection
Keywords: SARS-CoV-2 Vaccine
Coronavirus Virus Diseases
RNA COVID-19
COVID-19 Vaccine Arcturus
Self Amplifying RNA Vaccine
Variants of Concern
Lead sponsor: Arcturus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-09-08
Enrollment: 72
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will evaluate 3 investigational vaccines in parallel.
Primary purpose: TREATMENT

Brief summary: This is a Phase 1/2, randomized, observer-blind study in healthy adults. The study will evaluate the safety, reactogenicity, and immunogenicity of 3 SARS-CoV-2 self-amplifying RNA vaccine candidates against COVID-19 in adults previously vaccinated and not previously vaccinated against SARS-CoV-2.

Detailed description: The study will initially enroll approximately 72 adult participants into 2 cohorts (A and B). Cohort A is further sub-divided into two sub-cohorts which include 12 participants who are seronegative, not previously vaccinated at screening (Sub-cohort A1) and 24 participants who are seropositive, not previously vaccinated at screening (Sub-cohort A2).

Within the first cohort (Cohort A), Sub-cohort A1 will include a total of 12 adult participants ≥21 to ≤65 years of age who have not been previously vaccinated with a SARS-CoV-2 vaccine. Sub-cohort A2 will include a total of 24 adult participants ≥21 to ≤65 years of age who have not been previously vaccinated with a SARS-CoV-2 vaccine. Study vaccines will be given as 2 doses separated by 28 days.

The second cohort (Cohort B) will include a total of 36 adult participants ≥21 to ≤65 years of age who have been previously vaccinated (5 months or longer prior to study enrollment) with SARS-CoV-2 vaccine. Study vaccines will be given as single doses.

Additional cohorts may increase the age range of participants up to 80 years of age.

Eligibility criteria: Inclusion Criteria:

Individuals who:

1. Are able to provide consent
2. Agree to comply with all study visits and procedures
3. Are willing and able to adhere to study restrictions
4. Are sexually active and willing to adhere to contraceptive requirements
5. Are male, female, or transgender ≥21 to ≤80 years of age
6. For the previously vaccinated groups only, received 2 doses of SARS-CoV-2 vaccine 5 months or longer prior to study enrollment

Exclusion Criteria:

Individuals who:

1. For the unvaccinated groups only, previously received any investigational or authorized MERS-CoV, SARS-CoV, and SARS-CoV-2 vaccines (including ARCT-021)
2. For the previously vaccinated groups only, previously received BNT162b2 but have not received 2 doses within at least 5 months prior to study enrollment
3. Are planning to receive other COVID-19 vaccines during the study period
4. Recently received other vaccines
5. Have a fever or are feeling sick close to the time of the first study vaccination
6. Have a known history of COVID-19 disease or asymptomatic SARS-CoV-2 infection
7. Are pregnant or breastfeeding
8. Have had a severe reaction to previous vaccines
9. Have a severe or uncontrolled disease(s) that may interfere with the interpretation of the study
10. Have some respiratory diseases
11. Have some significant heart diseases
12. Have some neurological conditions
13. Have sickle cell disease or some other blood disorders
14. Have had a major surgery within the past 6 months
15. Have a history of chronic liver disease
16. Have a history of autoimmune disease or immunodeficiency
17. Have received allergy injections, interferon, immunomodulators, cytotoxic drugs or other similar toxic drugs.
18. Have received blood products
19. Have a positive test for hepatitis B or C or human immunodeficiency virus
20. Have uncontrolled hypertension
21. Have had cancer except for cancers that were treated and that have low risk of returning
22. Are obese
23. Are Investigator site staff members, employees of Arcturus or the contract research organization (CRO) directly involved in the conduct of the study, or site staff members otherwise supervised by the Investigator or immediate family members of any of the previously mentioned individuals

Primary outcomes:
measure: Percentage of participants reporting solicited local or systemic adverse events
timeFrame: For 7 days following each study vaccination
measure: Percentage of participants reporting unsolicited adverse events
timeFrame: For 28 days following each study vaccination
measure: Percentage of participants reporting medically attended adverse events
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: Percentage of participants reporting adverse events leading to discontinuation from study vaccine/study withdrawal
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: Percentage of participants reporting serious adverse events
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: SARS-CoV-2 serum neutralizing antibody levels, expressed as GMTs
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: Changes in SARS-CoV-2 serum neutralizing levels from before vaccination to each subsequent time point, expressed as GMFRs
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: Percentages of participants achieving greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 serum neutralizing antibody levels
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: GMC ratio (ARCT-021/ARCT-165, ARCT-165/ARCT-154, and ARCT-021/ARCT-154)
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: SARS-CoV-2 full-length spike, RBD, and N binding antibody levels, expressed as GMCs
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: Changes in SARS-CoV-2 full-length spike, RBD, and N binding antibody levels from before vaccination to each subsequent time point, expressed as GMFRs
timeFrame: Through Final Visit (365 days after last study vaccine dose)
measure: Percentages of participants achieving greater than or equal to 4-fold rise from before vaccination in SARS-CoV-2 full-length spike, RBD, and N binding antibody levels
timeFrame: Through Final Visit (365 days after last study vaccine dose)
Secondary outcomes:
Other outcomes:
Locations:
city: Wichita
country: United States
facility: Arcturus Investigational Site 202
state: Kansas
city: Kansas City
country: United States
facility: Arcturus Investigational Site 201
state: Missouri
city: Singapore
country: Singapore
facility: Arcturus Investigational Site 101
city: Diepkloof
country: South Africa
facility: Arcturus Investigational Site 301
state: Soweto
Study officials:
affiliation: Arcturus Therapeutics
name: Clinical Program Director
role: STUDY_DIRECTOR
References: