First in human study, with healthy volunteers, for a compound targeting the treatment of sepsis and septic shock. Other
Conditions
Interventions
Part A focusses on the safety, tolerability, pharmacokinetics and pharmacodynamic effects of Apta-1.
Part B (exploratory study part) explores the safety, tolerability, pharmacokinetics and pharmacodyn
Sponsors
Aptahem AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Applicable to part A and part B: 1. Has the ability to communicate well with the Investigator in the Dutch language and is willing and able to comply with all study procedures and give written informed consent prior to any study-mandated procedure. 2. Healthy male and female subjects,18 to 55 years of age, inclusive, at screening. 3. Body mass index (BMI) between 18 and 30 kg/m² and with a weight between 50 and 100 kg, both inclusive, at screening. 4. Female subjects of childbearing potential and male subjects who have sexual intercourse with a woman of childbearing potential must be willing to practice effective contraception during the study and be willing and able to continue contraception for respectively at least 180 days (females) or 90 days(males) after their last dose of study treatment. Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, unless they meet one of the following conditions: 4.1. Post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 weeks after surgical bilateral oophorectomy with or without hysterectomy; 4.2. Post-hysterectomy.
Exclusion criteria
Exclusion criteria: 1. Evidence of any active or chronic disease or condition (e.g. history of sepsis, cardiovascular disease, syncope or malignancy) that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator (following a detailed medical history, physical examination, vital signs (systolic and diastolic blood pressure, pulse rate, body temperature) and 12-lead electrocardiogram (ECG)). Minor deviations from the normal range may be accepted if judged by the Investigator to have no clinical relevance. 2. Clinically significant abnormalities, as judged by the investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. 3. Hemorrhagic diathesis (e.g. nose bleeds, mucosal bleedings, easy bruising, gastrointestinal bleeding, menorrhagia), as judged by the investigator. 4. Use of any prescription or OTC medications, antibiotics, NSAIDs (such as ibuprofen), aspirin, anti-platelet therapy, anti-coagulation therapy, prophylactic and therapeutic LMWH or un-fractioned heparin within 4 weeks, or 5 half-lives (whichever is longer), prior to first IMP administration. Exception for prescription contraceptives. 5. Any active or ongoing chronic inflammatory or infectious disease including periodontitis except for common viral or fungal skin infections such as plantar warts or athlete's foot. Additional criteria for part B: 1. Previous participation in a systemic (i.v./inhaled) LPS challenge trial or prior exposure to systemic endotoxin within a year before LPS administration in this study. 2. Significant risk or history of cardiac failure, overfilling and/or developing edema. 3. Estimated glomerular filtration rate (eGFR) of <90mL/min/1.73m².
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Treatment-related (serious) adverse events measured by inquiry to the subjects throughout the study (at screening, continuous during in-clinic period and follow-up). If abnormalities are indicated by the subjects, the details (including complaints, starttime, stoptime, diagnose, seriousness, relatedness) of the event will be stored in the database. 2. Concomitant medication measured by inquiry to the subjects throughout the study (at screening, continuous during in-clinic period and follow-up). Concomitant medications initiated, stopped, up-titrated or down-titrated for an AE will be recorded with all details (including used drug, starttime, stoptime, indication, route of administration, dose) and will be stored in the database. 3. Vital signs measured by valuations of systolic and diastolic blood pressure, pulse rate, respiratory rate, and temperature will be performed throughout the study using a Dash 3000, Dash 4000, Dynamap 400 or Dynamap ProCare 400. Timepoints: 3.1. Part A cohort 1: at screening, on day -1, on day 1 pre-dose and at +15m, +30m, +45m, +1h, +2h, +4h, +8h, +24h, +30h after dosing, and follow-up. 3.2. Part A cohort 2-6 and part B: at screening, on day -1, on day 1 pre-dose and at +15m, +30m, +45m, +1h, +1h15m, +1h30m, +1h45m, +2h, +4h, +8h, +24h, +30h after dosing, and follow-up. 4. Clinical laboratory tests measured by haematology, coagulation, chemistry (including glucose), serology and urinalysis will be conducted by an external laboratory; the laboratory of the Leiden University Medical Centre, using validated routine methodology. Timepoints: 4.1. Part A cohort 1: at screening, on day -1, on day 1 pre-dose and at +1h, +4h, +8h, +24h after dosing, and follow-up. 4.2. Part A cohort 2-6 and part B: at screening, on day -1, on day 1 pre-dose and at +1h, +2h, +4h, +8h, +24h after dosing, and follow-up. 5. Electrocardiogram parameters measured by ECGs will be obtained during the study using Marquette 2000/5500 and stored using the MUSE Cardiolog | — |
Secondary
| Measure | Time frame |
|---|---|
| PK-parameters (AUC0-1h, AUCinf, AUCinf(%extrap), AUClast, CL, Cmax-dose1, Cmax-dose2, t1/2, tmax, tlast, Vz) will be analysed by an external laboratory, the laboratory of Axolabs, using a validated AEX-HPLC method and dose-normalized PK parameters on total dose (AUCinf, AUClast, dose-normalizedPK parameters on separate dose: AUC0-1h, Cmax-dose1, Cmax-dose2) will be calculated by a pharmacometrician using non-compartmental analyses. Timepoints at which the blood samples for analysis are being drawn: Part A cohort 1: on day 1 pre-dose and at +15m, +30m, +45m, +1h, +1h30m, +2h, +4h, +8h, +24h, +30h after dosing. Part A cohort 2-6 and part B: on day 1 pre-dose and at +15m, +30m, +45m, +1h, +1h15m, +1h30m, +1h45m, +2h, +3h, +4h, +6h, +8h, +24h, +30h after dosing. | — |
Countries
Netherlands
Outcome results
None listed