COVID-19 MedDRA version: 23.1 Level: LLT Classification code 10084465 Term: COVID-19 vaccination System Organ Class: 100000004865
Conditions
Interventions
Product Name: AKS-452
Pharmaceutical Form: Solution for injection
Current Sponsor code: AKS-452
Other descriptive name: COVID-19 vaccine
Concentration unit: µg/ml microgram(s)/millilitre
Concentration
Sponsors
UMCG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-65 years (extremes included), males and females. This will be expanded to 85 years of age for phase II. - SARS-CoV-2 serology (an anti-SARS-Cov-2 SP-specific IgG ELISA): o Tests negative for IgG 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 o Note: one retest of vital functions and ECG is allowed within the screening window - No clinically significant laboratory abnormalities as determined by the investigator o 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 - For phase I: nNo invitation is received to get a registered vaccine within the first 2 months after the moment of participation in this study. For phase II this criterium will be abandoned as the whole population will have received an invitation to get a registered vaccine. Therefore, a participant should agree not to receive a registered vaccine within 28 days after receiving the last AKS-452 vaccine. - 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: o At least 1 year post-menopausal (amenorrhea >12 months and/or follicle-stimulating hormone >30 mIU/mL) at screening; o Surgically sterile (bilateral oophorectomy, hysterectomy, or tubal ligation); o 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 o 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. o Note: pregnancy testing will consist of a serum pregnancy test at screening and urine pregnancy tests at other (dosing) visits, in all women. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 176 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 176
Exclusion criteria
Exclusion criteria: - Pregnant of breast feeding 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 signs of 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 SARS-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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety, tolerability and humoral immunogenicity profile of AKS-452 following two injections administered 28 days apart in a combinatorial phase I/II single-center, open label clinical study.;Secondary Objective: Evaluate the cell-mediated immune responses to AKS-452 induced by two consecutive immunizations to estimate peak Ab titers and duration of Ab response.;Primary end point(s): To evaluate the safety, tolerability and humoral immunogenicity profile (i.e., SP/RBD-specific IgG titers) of AKS-452 following a one-injection regimen and a two-injection regimen administered 28 days apart in a combined Phase I/II single-center, open-label clinical study. - Main study parameter for phase I is safety and dose-finding in a classical 3x3 dosefinding design (In this phase I we have 6 cohorts), with an expansion to 10 subjects per dosing-cohort up to a total of 60 subjects (6x10) - Main study parameter for phase II is safety and initial efficacy measurement as a preparatory study towards a sufficient powered phase III study design. Phase II will consist of two-arms of 58 subjects per cohort all receiving the active vaccine.;Timepoint(s) of evaluation of this end point: 0, 28, 56, 90, and 180 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Anti-SARS-CoV-2 SP/RBD IgG titers at days 0, 28, 56, 90, and 180. - Serum titer inhibition of recombinant ACE2-SP/RBD binding and/or neutralization of live SARS-CoV-2 virus infection of live cells (Plaque Reduction Neutralization Test, PRNT) at days 0, 28, 56, 90, and 180. - T-cell responses measured ex vivo using PBMCs to measure SP/RBD-specific T cell production of IFN-g and Th1/Th2/Th17 related cytokines via ELISpot or other Ag-specific flowcytometric-based assays on days 0, 7(subset), 28, 35 (subset), 56, 90, and 180. ;Timepoint(s) of evaluation of this end point: 0, 7(subset), 28, 35 (subset), 56, 90, and 180 days | — |
Countries
Netherlands
Contacts
Public ContactGooitzen van Dam
University Medical Center Groningen
Outcome results
None listed