Phase IIa Randomized Placebo Controlled Clinical Study of Codivir in Hospitalized Patients With Moderate COVID-19

Study Overview
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Brief Summary
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This is a double-blind, multicentre, multinational study to evaluate the safety and collect preliminary efficacy data of Codivir drug product in 130 hospitalized adults with moderate COVID-19 symptoms. COVID-19 symptoms (fever, cough, myalgia and changes in smell or taste) onset must be within 7 days prior enrolment. Treatment will begin in the hospital, participants will be discharged according to medical decision and continue the treatment until to Day 7 at home and followed up to day 28.

Detailed Description
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eligible hospitalized participants will be recruited to the study and will receive standard of care treatments as well as Codivir or placebo, which will be administered at a dose of 20 mg SC, twice a day, for 7 days. If up to medical decision of the medical staff in the site, the patient should be released before Day 7, site study team will contact the medical monitor of the study to get the instructions. Participants will be followed up to the 28th day via phone contact. The phone visit will be performed to monitor the clinical symptoms, collect adverse events and concomitant medication and provide the patient with additional instructions, if relevant. If they have progressed well, they will continue the treatment up to Day 7 at home, receiving a nurse's home visit twice a day to administer Codivir and collect vital signs. Participants will be followed up to Day 28 by telemedicine. A doctor will call them periodically to monitor the clinical evolution, collect adverse events, concomitant medication and instruct the participants. In case of unfavorable evolution, the participants will remain hospitalized receiving the appropriate care. The investigator will decide whether or not the investigational medication will continue, considering the participant's health and well-being.

Official Title
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Phase IIa Randomized Placebo Controlled Clinical Study of Codivir in Hospitalized Patients With Moderate COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Covidir injections
* Diagnostic Test: Quantitative PCR SARS-CoV-2
* Diagnostic Test: IgM and IgG dosage
* Diagnostic Test: Screening Blood tests
* Diagnostic Test: Electrocardiogram
* Other: NEWS-2 score
* Other: WHO score
* Other: Physical examination
* Other: COVID-19-Related Symptoms assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 75 years Male or female SARS-CoV-2 infection indicated by confirmed RT-PCR test Moderate hospitalized COVID-19 (at least two out of three criterias below): Evidence of lower respiratory disease during clinical assessment (cough, fever, difficulty breathing) or imaging (X-rays) Oxygen saturation (SpO2) in room air < 93% <30 breaths per minute No signs of hemodynamic decompensation Absence of pregnancy in women of childbearing age Ability to understand and comply with the requirements of the protocol Consent to participate Consent to use at least one highly effective contraception methods (condoms, IUD, oral contraceptives) since the ICF signature and at least 30 days after the study. Exclusion Criteria: Patients receiving oxygen supplementation except of nasal prongs, nasal intermittent positive pressure ventilation (NIPPV) or high flow nasal cannula (HFNC) that are allowed to be enrolled to the study). Positive RT-PCR test more than 72 hours prior to enrolment. Onset of symptoms more than 7 days prior to enrolment. Participant using drugs that are under clinical investigation in last 30 days. Body mass index less than 19.9 or greater than 35. Comorbidities such as: other serious infections, active malignancies, autoimmune diseases, liver, kidney or heart failure; another systemic disease and / or laboratory abnormality, which, in the investigator's opinion, prevent the patient from participating in the study. Concomitant HIV, HBV or HCV infection. Pregnancy or lactation. Vaccination for any other infection in the 4 weeks prior to enrolment. Any condition that increases the risk of participating in the study, in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Group Assignment
Interventional Model Description: This is a double-blind, multicentre, multinational study to evaluate the safety and collect preliminary efficacy data of Codivir drug product in 130 hospitalized adults with moderate COVID-19 symptoms. COVID-19 symptoms (fever, cough, myalgia and changes in smell or taste) onset must be within 7 days prior enrolment.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Codivir treatment<br>20 mg administrated by subcutaneous (SC) injection, twice a day, for 7 days | Drug: Covidir injections<br>* administration of the investigational product CODIVIR/Placebo at a dose of 20 mg twice a day subcutaneously at visits Day0-Day6 (7 days total)<br>* Other names: Experimental drug administration;Diagnostic Test: Quantitative PCR SARS-CoV-2<br>* detection of viral RNA in nasopharyngeal and oropharyngeal samples by the Real Time Protein Chain Reaction technique.<br>Diagnostic Test: IgM and IgG dosage<br>* lood collection for dosage of Anti SARS-CoV-2 antibodies.<br>Diagnostic Test: Screening Blood tests<br>* omplete blood count, urea, creatinine, uric acid, sodium, potassium, chloride, calcium, glucose, glycated hemoglobin, alkaline phosphatase (FA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubins and fractions ( BTF), total proteins and fractions (PTF), lipid profile (total cholesterol, fractions and triglycerides); coagulogram (TP, aPTT); D-dimer; C-reactive protein; HIV, HBV, HCV serology; Ferritin; troponin, fibrinogen,Coagulogram (TP, aPTT); D-dimer, Pregnancy test for non-sterile women.<br>Diagnostic Test: Electrocardiogram<br>* valuation by the principal investigator or assistant physician with a complete physical examination<br>* Other names: ECG;Other: NEWS-2 score<br>* assessment of the participant by the NEWS-2 score.<br>Other: WHO score<br>* assessment of the participant by the score of the World Health Organization.<br>Other: Physical examination<br>* evaluation by the principal investigator or assistant physician<br>Other: COVID-19-Related Symptoms assessment<br>* will be completed by the study staff member based on patient status and answers.<br>|
| Placebo Comparator: Placebo treatment<br>Placebo administrated in subcutaneous (SC) injection, twice a day, for 7 days | Drug: Covidir injections<br>* administration of the investigational product CODIVIR/Placebo at a dose of 20 mg twice a day subcutaneously at visits Day0-Day6 (7 days total)<br>* Other names: Experimental drug administration;Diagnostic Test: Quantitative PCR SARS-CoV-2<br>* detection of viral RNA in nasopharyngeal and oropharyngeal samples by the Real Time Protein Chain Reaction technique.<br>Diagnostic Test: IgM and IgG dosage<br>* lood collection for dosage of Anti SARS-CoV-2 antibodies.<br>Diagnostic Test: Screening Blood tests<br>* omplete blood count, urea, creatinine, uric acid, sodium, potassium, chloride, calcium, glucose, glycated hemoglobin, alkaline phosphatase (FA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubins and fractions ( BTF), total proteins and fractions (PTF), lipid profile (total cholesterol, fractions and triglycerides); coagulogram (TP, aPTT); D-dimer; C-reactive protein; HIV, HBV, HCV serology; Ferritin; troponin, fibrinogen,Coagulogram (TP, aPTT); D-dimer, Pregnancy test for non-sterile women.<br>Diagnostic Test: Electrocardiogram<br>* valuation by the principal investigator or assistant physician with a complete physical examination<br>* Other names: ECG;Other: NEWS-2 score<br>* assessment of the participant by the NEWS-2 score.<br>Other: WHO score<br>* assessment of the participant by the score of the World Health Organization.<br>Other: Physical examination<br>* evaluation by the principal investigator or assistant physician<br>Other: COVID-19-Related Symptoms assessment<br>* will be completed by the study staff member based on patient status and answers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in World Health Organization Ordinal Scale for clinical improvement | change in World Health Organization Ordinal Scale for clinical improvement in the treatment group in comparison with Placebo. the scale min score - 0 and max score - 8. the higher the scores mean a worse outcome | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in COVID-19-Related Symptoms score (measured on days 7, 14, 21, 28) in the treatment group in comparison with Placebo). | Each symptom is scored individually using the following response options and scoring values: Items 1-10: None = 0; Mild = 1; Moderate = 2; and Severe = 3 Items 11 and 12: Not at all = 0; 1-2 times = 1; 3-4 times = 2; 5 or more times = 3 Items 13 and 14: Sense of smell/taste same as usual = 0; Sense of smell/taste less than usual = 1; No sense of smell/taste = 2. he higher the scores mean a worse outcome | up to 28 days | 
| adverse events | Incidence and severity of adverse events related to the investigational product in the treatment group in comparison with Placebo | up to 28 days | 
| RT-PCR viral load | Time to decreased RT-PCR viral load in the treatment group in comparison with Placebo | up to 28 days | 
| IgM & IgG anti-SARS-CoV-2 | Evolution of IgM & IgG anti-SARS-CoV-2 in the treatment group in comparison with Placebo | up to 28 days |