Preventive Dendritic Cell Vaccine, AV-COVID-19, in Subjects Not Actively Infected With COVID-19

Study Overview
=================
Brief Summary
-----------------
This is a phase 2 randomized, double-blind clinical trial testing an anti-SARS-CoV-2 COVID-19 vaccine (AV-COVID-19) made on site using PT AIVITA Biomedika Indonesia's vaccine-enabling kit for the prevention of COVID-19 infection. The product is a subject-specific personal vaccine that consists of autologous dendritic cells and lymphocytes (DCL) previously incubated with a quantity of SARS-CoV-2 spike protein (S-protein) which was shown to be safe in a phase 1 study also conducted in Indonesia. In this phase 2 study, efficacy is assessed via enhanced S-protein-specific T-cell response by comparing results before and after vaccination. Safety is confirmed via laboratory values, observation and regular patient reporting.

Detailed Description
-----------------
In this phase 2 study, a single dose of AV-COVID-19 DCL vaccine is injected subcutaneously in the forearm (left or right) at week 0 (day-0), to facilitate inspection and avoid confusion of local post-injection reactions or shoulder pain. Follow-up visits to assess safety are performed at 1, 2, and 4 weeks after vaccination, with laboratory safety tests performed at weeks 1 and 4, and only at week 2 if any clinically significant changes at screening up to week 1. At each visit, the injection site is assessed, and the subject is asked about symptoms, and at weeks 0 (baseline before injection), 2 and 4, blood is drawn for immunogenicity testing. Reaction data at the injection site and safety profile are obtained by telephone to subjects on days 1, 2, and 3 after vaccine injection. Subjects are asked specifically about local injection site reactions and systemic flu-like symptoms (fever, chills, muscle aches, joint pain) for 7 days after injection. Adverse events (AE) are collected for 28 days after injection. Evaluation of laboratory tests for clinical safety parameters are carried out at screening as well as immediately before vaccination and on day 7 and day 28 post-vaccination. Serious adverse events (SAE), recent medical conditions, and other events requiring medical intervention are recorded for 2 months after vaccination. Vaccine enabling kits are made by PT AIVITA Biomedika Indonesia. All vaccines are made in Indonesia on site at participating hospitals and clinical sites.

Official Title
-----------------
Phase II Randomized Double Blind Clinical Trial Three Preventive Vaccine Formulations Consisting of Autologous Dendritic Cells and Lymphocytes Incubated With Different Quantities of Spike Protein Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), in Subjects Not Proven Actively Infected or Never Infected With COVID-19

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Biological: AV-COVID-19


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Understands and agrees to comply with research procedures and provides written informed consent Physical and mental health meet criteria to participate, which includes factors associated with increased risk of exposure to SARS-CoV-2, such as age > 65, mild to moderate obesity (BMI 30-40), hypertension controlled with medication, drug controlled hyperlipidemia, diabetes controlled with medication, mild chronic lung disease Vein access permits for blood collection For people with reproductive ability, adequate contraception and negative pregnancy test for women Exclusion Criteria: Have active symptoms of COVID-19 infection Diagnosed with COVID-19 with a positive PCR test in the past 3 months Positive SARS-CoV-2 rapid antibody IgG test Positive pregnancy test Known to have immunodeficiency disease Are taking immunosuppresive drugs and/or corticosteroids in the long term Have a condition requiring oxygen supplementation Previously diagnosed with invasive cancer and receiving anti-cancer therapy in addition to hormonal therapy for breast or prostate cancer History of thromboembolism or genetic predisposition to thromboembolism, or being on anti-thromboembolic therapy other than low-dose aspirin Physical or mental disability that prevents you from carrying out normal daily activities In the Investigator's judgement, have illnesses or medical conditions that could preclude participation Excessive obesity: BMI > 40 Uncontrolled hypertension: systolic > 180, diastolic > 100 Not willing to sign written consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AV-COVID-19 (0.1 mcg S-protein)<br>DCL previously incubated with 0.1 mcg spike protein | Biological: AV-COVID-19<br>* DCL previously loaded with varying quantity of S-protein<br>|
| Experimental: AV-COVID-19 (0.33 mcg S-protein)<br>DCL previously incubated with 0.33 mcg spike protein | Biological: AV-COVID-19<br>* DCL previously loaded with varying quantity of S-protein<br>|
| Experimental: AV-COVID-19 (1.0 mcg S-protein)<br>DCL previously incubated with 1.0 mcg spike protein | Biological: AV-COVID-19<br>* DCL previously loaded with varying quantity of S-protein<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy based on T-cell-induced immune response | ELISPOT assay at baseline, week 2 and week 4 post-vaccination | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event frequency and incidence | Confirm safety of AV-COVID-19 via laboratory values and adverse event reporting from baseline to 28-days post-vaccination | 4 weeks | 
| Optimal formulation | Choose the optimal formulation (0.1, 0.33, 1.0 mcg S-protein) | 4 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prevention