Acute respiratory distress syndrome (ARDS) in COVID-19 infection
Conditions
Interventions
Product Name: KAND567
Product Code: KAND567
Pharmaceutical Form: Capsule
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use
Sponsors
Kancera AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written Informed Consent obtained and documented according to ICH/GCP and national/local regulations prior to any study-specific procedure. 2. Males and females aged =18-85 years at the time of signing the informed consent form. Female subjects must be post-menopausal or use contraceptive methods with a failure rate of 300 ng/mL for men and > 150 ng/mL for women B. C-reactive protein (CRP): = 10 mg/L C. D-dimer elevated above the age-adjusted lower limit: i. = 50 years; 50 years; age-related, calculated as follows: 0.5 mg/L FEU + 0.01 mg/L FEU for every year over 50 (i.e. one who is 70 years old has thus a reference limit of =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: 1. Patient not committed to aggressive management. For example, the subject, the subject's family or primary physician are unwilling to accept that the subject is placed on mechanical ventilation; or in the case of an advanced directive to withhold life support, with the exception of cardiopulmonary resuscitation. 2. A suspected, active bacterial, fungal, viral, or other infection (besides COVID 19). 3. Alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) > 2 times the upper limit of normal (ULN) detected at screening (per local lab) or suspected liver disease. 4. Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or decompensated congestive heart failure. 5. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g. compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. 6. Clinically verified pulmonary embolism 7. Chronic inflammatory disease requiring treatment with oral corticosteroids in a dose higher than prednisone 10 milligrams (mg) or equivalent per day, or requiring treatment with other anti-inflammatory drugs (e.g. methotrexate). 8. Use of strong CYP3A4 inhibitors (e.g. azoleantifungals, macrolide antibiotics, protease inhibitors) or inducers (e.g. rifabutin and rifampicin) and drugs sensitive to CYP3A4 inhibition (e.g. benzodiazepines, certain statins [lovastatin and simvastatin], certain P2Y12 inhibitors [ticagrelor and clopidogrel]). 9. Participation in another pharmaceutical clinical study. 10. Subject who has received any investigational drug within the last 3 months before administration of the investigational medicinal product (IMP). 11. Severe COVID-19 at randomization: requiring non-invasive or invasive mechanical ventilation or ICU admission for any other cause than respiratory support. 12. Patients judged not to be suitable for non-invasive monitoring of oxygen saturation because of impaired peripheral circulation or for other reasons. 13. Active malignancy with or without treatment, except local basal cell carcinoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the impact of oral administration of KAND567 versus placebo, in COVID-19 subjects admitted to the hospital for care of COVID-19 infection with respect to: Rates of adverse events (AEs), serious adverse events (SAEs) and safety lab data. ;Secondary Objective: The secondary objectives are to determine and compare the effects of oral administration of KAND567 versus placebo, on: a. Oxygen exchange and respiration in subjects admitted to the hospital for care of COVID-19 infection. b. Clinical outcome measures reflecting the severity and progression of disease. c. The effect on different types of leukocytes and cytokines. Further, the study will evaluate the population pharmacokinetics (PK) of KAND567 after oral administration to COVID-19 subjects, and by sparse blood gas sampling add an estimate of PaO2 to confirm non-invasive measurements of oxygenation. ;Primary end point(s): Occurrence of Adverse Events and Serious Adverse Events ;Timepoint(s) of evaluation of this end point: After subject has signed informed consent and during participation in the study until final follow-up visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The assessment will be done by comparing the effects on the ROX index, defined as the ratio of oxygen saturation as measured by pulse oximetry/fraction-inhaled oxygen to respiratory rate (ROX = O2 Sat/FiO2 x RR), in the two treatment arms. b. Treatment failure rate, where treatment failure is defined as use of assisted invasive mechanical ventilation or death c. Time to assisted invasive mechanical ventilation (measured with hourly precision). d. Time to admission to ICU (measured with hourly precision). e. Number of days hospitalized. f. The WHO Covid-19 Ordinal Scale of Clinical Improvement 3. The individual components of the ROX index 4. The levels of different blood cells types and activity markers before and after administration of KAND567 5. The fractalkine phenotype on T-cells, monocytes, NK-cells and neutrophils 6. Plasma levels of cytokines such as IL-6 and the inflammation marker CRP before and after KAND567 administration 7. The PK of the present study will be compared to PK as determined in the previous phase I clinical study KAN0001. 8. PaO2/FiO2 change from baseline The safety endpoint parameters are frequency and severity of adverse events, vital signs, electrocardiography (ECG), results of safety laboratory tests and urinalysis. .;Timepoint(s) of evaluation of this end point: After subject has signed informed consent and during participation in the study until final follow-up visit | — |
Countries
Denmark, Sweden
Contacts
Public ContactAnna Runeson
Scandinavian CRO AB
Outcome results
None listed