A Phase 1/2 Study to Determine Safety and Immunogenicity of Two COVID 19 Vaccines VB10.2129 (RBD Candidate) and VB10.2210 (T Cell Candidate) Previously Vaccinated in Healthy Adult Volunteers

Study Overview
=================
Brief Summary
-----------------
An open label, dose escalation, and dose expansion study to evaluate the safety, reactogenicity and immunogenicity of two SARS-CoV-2 DNA plasmid vaccine candidates, VB10.2129 (C1) and VB10.2210 (C2). tThree dose levels will be tested. IM administrations 21 days apart. Part 1 is a dose escalation phase and Part 2 is a dose expansion phase. In Part 2 a selected dose will be tested further in additional healty volunteers.

Detailed Description
-----------------
This is an open label, dose escalation, and dose expansion study designed to evaluate the safety, reactogenicity and immunogenicity of two SARS-CoV-2 or COVID-19 DNA plasmid vaccine candidates, VB10.2129 (C1) and VB10.2210 (C2). Part 1 is a dose escalation phase and Part 2 is a dose expansion phase and both vaccine candidates, ie, VB10.2129 (C1) and VB10.2210 (C2) will be tested. Part 1 consist of two arms: one arm with each vaccine candidate and each arm investigating three escalating dose levels. 10 subjects previously vaccinated with an mRNA vaccine will be enrolled at each dose level. Each subject will receive two vaccinations 21 days apart (Day 0 and Day 21). In Part 2 is a dose expansion phase with one arm for each candidate; VB10.2129 and VB10.2210, in previously vaccinated healthy subjects only. The dose to be investigated will be selected based on safety and inital immune response data from Part 1. All subjects will be folowed for up to 1 year after the first vaccination.

Official Title
-----------------
A Phase 1/2, Open Label, Dose Escalation Study to Determine Safety and Immunogenicity of Two (Prophylactic) COVID 19 DNA Vaccine Candidates (VB10.2129 [C1], a RBD Candidate and VB10.2210 [C2], a T Cell Candidate), in Healthy Adult Volunteers

Conditions
-----------------
COVID-19, Infection Viral, Infections

Intervention / Treatment
-----------------
* Biological: VB10.2129
* Biological: VB10.2210


Participation Criteria
=================
Eligibility Criteria
-----------------
Main inclusion criteria: Give informed consent by signing the Informed Consent Form (ICF) SARS CoV 2 vaccination status for Part 1: VB10.2129 (C1): have received 2 or 3 doses of an approved mRNA SARS CoV 2 vaccine, minimum 4.5 months (20 weeks) prior to Visit 1. VB10.2210 (C2): have received 2 doses (primary vaccination) or 3 (primary and boost) doses of an approved mRNA SARS CoV 2 vaccine, minimum 8 weeks prior to Visit 1. SARS CoV 2 vaccination status for Part 2: VB10.2129 (C1) and VB10.2210 (C2) Vaccination status prior to Visit 1 will be decided based on data from Part 1. Willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions (eg, local law and regulations [county specific lock down rules] regarding COVID-19), and other requirements of the study. Healthy, in the clinical judgement of the Investigator, based on medical history, physical examination, 12-lead electrocardiogram (ECG), vital signs (systolic/diastolic blood pressure, pulse rate, body temperature, respiratory rate), and clinical laboratory tests (blood chemistry, haematology, and urine chemistry) at Visit 0 (Screening). Women of childbearing potential (WOCBP) must have a negative pregnancy test and must agree to practice a highly effective form Agree not to be vaccinated with any other vaccine during the study until 28 days after receiving the last study vaccination Negative rtPCR-test for SARS-CoV-2 Main exclusion criteria: Have had any acute illness with or without fever, within 72 hours prior to the first vaccination Symptoms of upper respiratory infection, fever, persistent cough, shortness of breath, runny nose and breathing difficulties Breastfeeding or who plan to breastfeed during the study Have a known allergy, hypersensitivity, or intolerance to aminoglycosides Had any clinically significant or chronic medical condition or any major surgery within the past 5 years which Have any surgery planned during the study Had any chronic use of any systemic medications, including immunosuppressant's, oral corticosteroids or other immune-modifying drugs, within the 12 months prior to Screening Received any vaccination within the 28 days prior to Screening Received any prescription medicines (except hormonal contraception for WOCBP) within 14 days prior to Visit 0 (Screening) or over the counter medicines (except paracetamol and acetaminophen at a dose of (≤2 grams/day)) within 48 hours of Visit 0. Have a known history or a positive test of HIV 1 or 2, Hep B, or Hep C Have a positive rtPCR test for SARS-CoV-2 within 2 days of Screening Documented history of previous infection with SARS-CoV-2 and/or who have the presence of serum Ab indicative of a previous SARS-CoV-2 infection Have a history of hypersensitivity or have had a serious reaction to a previous vaccination Have any abnormality or permanent body art (eg, tattoo) that, would obstruct the ability to observe local reactions at the injection site. Have a condition known to put them at high risk for severe COVID-19, including those with any of the following risk factors: Hypertension, diabetes mellitus, chronic pulmonary disease, asthma, chronic liver disease, known stage 3 or worse chronic kidney disease Anticipating the need for immunosuppressive treatment within the next 6 months. Other inclusion or exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two vaccine candidates are investigated in parallell.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VB10.2129 Part 1 Dose escalaton<br>0.3 mg, 1 mg or 3 mg will be administered by two IM injections 21 days apart. | Biological: VB10.2129<br>* 0.3 mg, 1 mg or 3 mg on Day 0 and Day 21 or 3 mg on Day 0<br>|
| Experimental: VB10.2210 Part 1 Dose escalation<br>0.3 mg, 1 mg or 3 mg will be administered by two IM injections 21 days apart. | Biological: VB10.2210<br>* 3 doses (dose to be determined) on Day 0 and Day 21 or highest dose (TBD) on Day 0<br>|
| Experimental: VB10.2129 Part 2 Dose expansion<br>The seleceted dose from Part 1 will be administered IM in a two-dose schedule. | Biological: VB10.2129<br>* 0.3 mg, 1 mg or 3 mg on Day 0 and Day 21 or 3 mg on Day 0<br>|
| Experimental: VB10.2210 Part 2 Dose expansion<br>The seleceted dose from Part 1 will be administed IM in a two-dose schedule. | Biological: VB10.2210<br>* 3 doses (dose to be determined) on Day 0 and Day 21 or highest dose (TBD) on Day 0<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and frequency of local and systemic solicited adverse events (AEs) | As self reported in eDiary | Day 0 to Day 7 days after each vaccination | 
| Incidence and frequency of local and systemic unsolicited AEs | As elicited by investigator | Day 0 to Day 49 | 
| Incidence and frequency of serious AEs (SAEs) | As elicited by investigator | Day 0 to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral responses against SARS-CoV-2 | Number participants with increase in Ab titre and neutralizing Ab responses after first and second vaccine and long term responses (VB10.2129) | Day 0 (before Dose 1) up to 1 year | 
| Cellular responses (T-cell responses) to SARS-CoV-2 RBD epitopes by ELISpot | Number of participants with change from baseline in Antigen-Specific T-cell cytokine production and long term T-cell responses | Day 0 (before Dose 1) up to 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccine, COVID-19, Coronavirus, DNA vaccine