Anti-COVID19 AKS-452 Fusion Protein Vaccine - ACT Study

Study Overview
=================
Brief Summary
-----------------
Combinatorial phase I/II safety, tolerability and immunogenicity single center open-label clinical study of AKS-452 COVID-19 vaccination study

Detailed Description
-----------------
The study is designed as a combinatorial single-center open-label phase I and II clinical study design: I. a phase I dose-finding and safety / tolerability study combined with, II. a phase II safety / efficacy study on the biological activity of AKS-452 against COVID-19. To warrant more extensive development towards a phase III clinical study. The study will have a duration of approximately 4 months and will be executed at the University Medical Center Groningen, The Netherlands supported by the subsidizing party Akston Biosciences.

Official Title
-----------------
Anti-COVID19 AKS-452 Phase I/II VaccinaTion Study

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: AKS-452


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: SARS-CoV-2 serology by Akston (a quantitative anti-SARS-Cov-2 SP/RBD-specific IgG ELISA): Undetectable or < 5 μg/mL titer and no known prior SARS-Cov-2 infection Body mass index (BMI) between 19.0 and 30.0 kg/m2, inclusive General good health, without significant medical illness, as determined via physical exam findings, ECG or vital signs Note: one retest of vital functions and ECG is allowed within the screening window - No clinically significant laboratory abnormalities as determined by the investigator Note: one retest of lab tests is allowed within the screening window Informed Consent Form signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose and procedures required for the study and is willing to participate in the study Willing to adhere to the prohibitions and restrictions specified in this protocol Non-smoker (including prior smokers having stopped smoking for more than 3 months at time of screening) or non-habitual smoker (habitual smokers are persons who smoke more than 4 cigarettes or other tobacco products on a weekly basis) and agree to not use tobacco products during confinement. Negative alcohol breath test and urine drug screen at screening and upon check-in at the clinical site. Negative hepatitis panel (including hepatitis B surface Ag and anti-hepatitis C virus Abs) and negative human immunodeficiency virus Ab and Ag screens at screening Female subjects should fulfil one of the following criteria: At least 1 year post-menopausal (amenorrhea >12 months and/or follicle stimulating hormone >30 mIU/mL) at screening; Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation); Will use adequate forms of contraceptives from screening to discharge. - Female subjects of childbearing potential and male subjects who are sexually active with a female partner of childbearing potential must agree to the use of an effective method of birth control from screening to discharge Note: medically acceptable methods of contraception that may be used by the subject and/or partner include combined oral contraceptive, contraceptive vaginal ring, contraceptive injection, intrauterine device, etonogestrel implant, double barrier, sterilization and vasectomy - Female subject has a negative pregnancy test at screening and upon check-in at the clinical site. Note: pregnancy testing will consist of a serum pregnancy test at screening and urine pregnancy tests at other (dosing) visits, in all women. Exclusion Criteria: A potential subject who meets any of the following criteria will be excluded from participation in this study: Pregnant of breastfeeding females Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, hematologic, rheumatologic, endocrine, autoimmune, or renal disease Any laboratory test which is abnormal, and which is deemed by the Investigator(s) to be clinically significant Behavioral or cognitive impairment or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the study protocol Current alcohol/illicit drug/nicotine abuse or addiction: history or evidence of current drug use or addiction (positive drug screen for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates) or excessive use of alcohol at screening and Day -2. Presence of any febrile illness (T > = 38.0°C or lab confirmed viral disease (PCR)) or symptoms suggestive of a viral respiratory infection within 1 weeks prior to vaccination Use of corticosteroids (excluding topical preparations for cutaneous or nasal use) or use of immunosuppressive drugs within 30 days before inoculation A history of anaphylaxis, history of allergic reaction to vaccine, known allergy to one of the components in AKS-452. Mild allergies without angio-oedema or treatment need can be included if deemed not to be of clinical significance (including but not limited to allergy to animals or mild seasonal hay fever) A history of asthma within the past 10 years, or a current diagnosis of asthma or reactive airway disease associated with exercise Receipt of a licensed vaccine within 4 weeks prior to viral inoculation Received any experimental SARA-CoV-2 vaccine or drug Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to vaccination. Receipt of another investigational agent within 30 days or 5 times the product half-life (whichever is longest) prior to vaccination Shares household with /works with immunocompromised individual(s), adults with significant cardiopulmonary disease, persons with significant asthma, institutionalized elderly or elderly with functional disability Deprived of freedom by an administrative or court order or in an emergency setting - Any condition that in the opinion of the principal investigator (PI) would jeopardize the safety or rights of a person participating in the trial or would render the person unable to comply with the protocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 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: Single Group Assignment
Interventional Model Description: Single-center, open-label, combinatorial safety, tolerability and exploratory efficacy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AKS-452 s.c.(A)<br>Subcutaneous injection of pre-defined dose (22,5 ug, 125 uL) single-dose | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: AKS-452 s.c. (B)<br>Subcutaneous injection of pre-defined dose (22,5 ug, 125 uL), two-dose | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: AKS-452 s.c. (C)<br>Subcutaneous injection of pre-defined dose (45 ug, 205 uL), single-dose | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: AKS-452 s.c. (D)<br>Subcutaneous injection of pre-defined dose (45 ug, 250 uL), two-dose | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: AKS-452 s.c. (E)<br>Subcutaneous injection of pre-defined dose (90 ug, 500 uL), single-dose | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: AKS-452 s.c. (F)<br>Subcutaneous injection of pre-defined dose (90 ug, 500 uL), two-dose | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: Phase 2, single-dose injection<br>Subcutaneous injection of selected dose based on phase 1 data, dose (90 ug, 500 uL) | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|
| Experimental: Phase 2, two-dose injection<br>Subcutaneous injection of selected dose based on phase 1 data, dose (45 ug, 500 uL) twice. | Biological: AKS-452<br>* s.c. or i.m. vaccination<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety / Tolerability | CTCAE-scoring | 35 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity | Antibody response COVID-19 | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
vaccine, safety, immunogenicity, dose-finding, exploratory efficacy