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

• ClinicalTrials.gov Identifier: NCT04374032
• Recruitment Status: Completed
• First Posted: May 5, 2020
• Last Update Posted: December 24, 2020
• Sponsor: Bosnalijek D.D
• Information provided by (Responsible Party): Bosnalijek D.D

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
COVID-19 Infection	Drug: metenkefalin + tridecactide; Drug: The standard of care	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Open-label, prospective, randomized, comparative, multiple doses applied in addition to the standard of care treatment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 1, 2020
• Actual Primary Completion Date: October 7, 2020
• Actual Study Completion Date: November 3, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ENKORTEN	Drug: metenkefalin + tridecactide; ENKORTEN® 5 mg + 1 mg Lyophilisate for Solution for Injection
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

Outcome Measures

Primary Outcome Measures :

1. Time to onset of change in the patient's clinical condition [ Time Frame: 21 day ]
   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.
2. Safety and tolerability evaluation - treatment-related adverse events will be assessed by CTCAE [ Time Frame: 21 day ]
   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.

Secondary Outcome Measures :

1. Length of in-hospital stay [ Time Frame: 21 day ]
   To monitor the period of patient's hospitalization
2. Survival rate [ Time Frame: 21 day ]
   To monitor the survival rate during the hospitalization
3. Intubation rate [ Time Frame: 21 day ]
   To monitor the intubation frequency during the hospitalization
4. Proinflammatory markers levels [ Time Frame: 21 day ]
   To monitor the levels of proinflammatory markers during the hospitalization (IL-6)

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Bosnia and Herzegovina

Clinical Center University of Sarajevo

Sarajevo, Sarajevo Canton, Bosnia and Herzegovina, 71000

University Clinical Centre of the Republic of Srpska

Banja Luka, Bosnia and Herzegovina, 78000

University Clinical Hospital Mostar

Mostar, Bosnia and Herzegovina, 88000

Hospital Travnik

Travnik, Bosnia and Herzegovina, 72270

Cantonal Hospital Zenica

Zenica, Bosnia and Herzegovina, 72000

Sponsors and Collaborators

Bosnalijek D.D

Investigators

• Principal Investigator: Rusmir Baljić, PhD; Clinical Center University of Sarajevo

More Information

• Responsible Party: Bosnalijek D.D
• ClinicalTrials.gov Identifier: NCT04374032
• Other Study ID Numbers: EN-COVCS-01
• First Posted: May 5, 2020
• Last Update Posted: December 24, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Disease Attributes; Pathologic Processes; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Enkephalin, Methionine; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs