Clinical Trial to Evaluate the Efficacy and Safety of an Immunomodulatory Therapy for the Treatment of Patients With Moderate to Severe COVID-19 Infection

Study Overview
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Brief Summary
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An Open-label, prospective, randomized, comparative, multiple doses applied in addition to the standard of care treatment of patients with moderate to severe COVID-19 infection

Detailed Description
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The justification for the use of immunomodulatory therapy is based on the evidence that drugs that are inhibitors of interleukin IL6 may prevent the more severe lung tissue damage caused by cytokine release in patients with more severe COVID19. Several studies have suggested a cytokine storm caused by the release of IL-6, IL-1, IL-12 and IL-18 with tumor necrosis factor TNF alpha and other inflammatory mediators. Increased inflammatory response of lung tissue may result in increased gas exchange at the alveolar-capillary level making oxygenation difficult in patients with more severe forms of the disease and the need for mechanical ventilation. In this regard, it is hypothesized that the use of immunomodulatory therapy should have an effect in reducing the lethal outcome, the need for oxygen therapy, and mechanical ventilation.

Official Title
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An Open-label, Prospective, Randomized, Comparative Clinical Trial to Evaluate the Efficacy and Safety of ENKORTEN® as an Immunomodulatory Therapy, Within the Usual Therapeutically Established Protocol, for the Treatment of Patients With Moderate to Severe COVID-19 Infection

Conditions
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COVID-19 Infection

Intervention / Treatment
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* Drug: metenkefalin + tridecactide
* Drug: The standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with laboratory-confirmed (PCR) COVID-19 infection Patients with moderate to severe COVID-19 infection Hospitalized patients on clinical centers and cantonal hospitals Patients with radiology-confirmed pneumonia within the clinical condition of COVID-19 infection including pulmonary opacity Patients with a clinical indication for pneumonia: increased body temperature (defined as a value above ≥ 36.6⁰C axillary route, ≥ 37.2°C oral route or ≥ 37.8 °C rectal route), and/or dyspnea, and/or cough, and/or SpO2 <96% Patients aged above 18, both genders Patients able and willing to understand the study, adhere to all study procedures and sign a written Informed Consent Form (ICF) prior to entering the study or with the assistance of the witness Exclusion Criteria: Patients not COVID-19 positive Patients with mild COVID-19 infection Patients who are study subjects in another clinical study for another investigational agent for COVID-19 Patients with malignant hypertension Patients with malignant disease and who are treated for malignant diseases in the last 5 years Patients with severe liver and kidney insufficiency Patients who are receiving therapy with an immunomodulatory or immunosuppressive agent Patients aged below 18, female patients who are pregnant or breastfeeding Known allergy to study drug or any component thereof Use of haloperidol, dopamine antagonists, or nonsteroidal anti-inflammatory drugs, except paracetamol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, prospective, randomized, comparative, multiple doses applied in addition to the standard of care treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ENKORTEN<br> | Drug: metenkefalin + tridecactide<br>* ENKORTEN® 5 mg + 1 mg Lyophilisate for Solution for Injection<br>|
| Other: The standard of care treatment<br>The usual therapeutically established protocol for the treatment of patients with moderate to severe COVID-19 infection | Drug: The standard of care<br>* The usual therapeutically established protocol, for the treatment of patients with moderate to severe COVID-19 infection prescribed by The Agency for medicinal products and medical devices of Bosnia and Herzegovina<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of change in the patient's clinical condition | The time of onset of improvement in the patient's clinical condition will be measured following the clinical objective and subjective signs and radiological indicators. | 21 day | 
| Safety and tolerability evaluation - treatment-related adverse events will be assessed by CTCAE | At every examination/evaluation, all AEs, whether noticed by investigators and their associates in the trial, or spontaneously reported by the subjects, or given as answer to direct question, must be evaluated by the investigator and reported on case report forms for AE. AE will be recorded in the e-CRF. Three-degree scale will be used for assessment of AE's severity: mild, moderate, severe. | 21 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of in-hospital stay | To monitor the period of patient's hospitalization | 21 day | 
| Survival rate | To monitor the survival rate during the hospitalization | 21 day | 
| Intubation rate | To monitor the intubation frequency during the hospitalization | 21 day | 
| Proinflammatory markers levels | To monitor the levels of proinflammatory markers during the hospitalization (IL-6) | 21 day |