E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute respiratory distress syndrome (ARDS) in COVID-19 infection |
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E.1.1.1 | Medical condition in easily understood language |
Acute respiratory distress syndrome (ARDS) in COVID-19 infection |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to determine and compare the effects of oral administration of KAND567 versus placebo, on oxygen exchange and respiration in subjects admitted to the hospital for care of COVID-19 infection.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are 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: a. Rates of adverse events (AEs) and serious adverse events (SAEs). 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 ≥18-75 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 < 1% to prevent pregnancy*. Male subject must be willing to use condoms with spermicide, and if he has a fertile partner, she must use contraceptive methods with a failure rate of < 1% to prevent pregnancy*. Male subjects must also refrain from donating sperm from the first dose until three months after dosing with investigational product (IP). * Combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal); progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD) or intrauterine hormone-releasing system (IUS); bilateral tubal occlusion, vasectomy, sexual abstinence. 3. Patients with symptoms and signs of SARS-CoV-2 infection according to WHO case definition. Symptoms must include shortness of breath, with an onset which occurred ≤ 1 week before admission, and the COVID-19 diagnosis must be confirmed by laboratory testing (PCR-positive). In addition, moderately impaired oxygenation as demonstrated by oxygen saturation ≤ 93% but ≥ 87% on room air, or requiring 1-5 L/min of oxygen to obtain an oxygen saturation of 92%, and at least one of the following laboratory values: A. Ferritin: > 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: > 0.5 mg/L i. ≤ 50 years; < 0.5 mg/L FEU i.ii. > 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 < 0.7 mg/L FEU; on who is 90 years old has a reference limit of < 0.9 mg/L FEU) 4. Able to swallow capsules. 5. Willingness and ability to comply with study procedures, visit schedules, study restrictions and requirements. |
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E.4 | Principal 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. Repeated (>2) episodes of diarrhea during the last 24 hours before randomization. 6. Clinically suspected and verified pulmonary embolism 7. Chronic treatment of inflammatory disease (e.g. oral corticosteroids). 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary 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.
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E.5.1.1 | 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 |
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E.5.2 | Secondary end point(s) |
1. Occurrence of AEs and SAEs 2. Clinical outcome measures a. Treatment failure rate, where treatment failure is defined as use of assisted invasive mechanical ventilation or death b. Time to assisted invasive mechanical ventilation (measured with hourly precision). c. Time to admission to ICU (measured with hourly precision). d. Number of days hospitalized. e. The WHO Covid-19 Ordinal Scale of Clinical Improvement 3. The individual components of the primary endpoint. 4. The levels of different blood cells types and activity markers before and after administration of KAND567 5. The fractalkine receptor 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 KAN0001 clinical study. 8. PaO2/FiO2 change from baseline
The safety endpoint parameters are frequency and severity of AEs, vital signs, electrocardiography (ECG), and the results of safety laboratory tests and urinalysis. |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |