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

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

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

Study Overview

• Status: Completed
• Conditions: COVID-19 Infection
• Intervention / Treatment: Drug: metenkefalin + tridecactide; Drug: The standard of care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Centre of the Republic of Srpska
  • Mostar, Bosnia and Herzegovina, 88000
    • University Clinical Hospital Mostar
  • Travnik, Bosnia and Herzegovina, 72270
    • Hospital Travnik
  • Zenica, Bosnia and Herzegovina, 72000
    • Cantonal Hospital Zenica
  • Sarajevo Canton
    • Sarajevo, Sarajevo Canton, Bosnia and Herzegovina, 71000
      • Clinical Center University of Sarajevo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ENKORTEN	Drug: metenkefalin + tridecactide; ENKORTEN® 5 mg + 1 mg Lyophilisate for Solution for Injection
Other: The standard of care treatment; The usual therapeutically established protocol for the treatment of patients with moderate to severe COVID-19 infection	Drug: The standard of care; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bosnalijek D.D
• Investigators: Principal Investigator: Rusmir Baljić, PhD, Clinical Center University of Sarajevo

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): October 7, 2020
• Study Completion (Actual): November 3, 2020

Study Registration Dates

• First Submitted: April 30, 2020
• First Submitted That Met QC Criteria: May 4, 2020
• First Posted (Actual): May 5, 2020

Study Record Updates

• Last Update Posted (Actual): December 24, 2020
• Last Update Submitted That Met QC Criteria: December 23, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enkephalin, Methionine
• Other Study ID Numbers: EN-COVCS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No