COLchicine Versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients With COVID-19

Study Overview
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Brief Summary
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Patients with mild and severe coronavirus disease 2019 (COVID 19) will be randomized 3:1:1:3 into four groups: colchicine, ruxolitinib, secukinumab, and control groups. . Patients will be follow-up during 45 days after randomization. Change in clinical assessment score COVID 19 (CAS COVID 19) between baseline and 12th day will be evaluated as the primary endpoint. Risk of death or mechanical ventilation during 45 days after randomization will also be assessed

Official Title
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COLchicine Versus Ruxolitinib and Secukinumab in Open-label Prospective Randomized Trial in Patients With COVID-19

Conditions
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COVID 19

Intervention / Treatment
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* Drug: Colchicine
* Drug: Ruxolitinib 5 MG
* Drug: Secukinumab 150 MG/ML Subcutaneous Solution [COSENTYX]
* Other: standard therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed inform consent COVID 19 with the mild and severe course. The diagnosis could be made with positive polymerase chain reaction (PCR) (International Statistical Classification (ICD-10) code - U07.1) and/or virus pneumonia in computer tomography (ICD 10 code - U07.2) Lung exposure on CT more than 25% Sp02 without supportive oxygen ≤ 93% C-reactive protein > 60 mg/l or elevation of C reactive protein 3 times in 8-14 days after first symptoms Exclusion Criteria: pregnancy and breastfeeding hypersensitivity to colchicine hypersensitivity to ruxolitinib hypersensitivity to secukinumab Known liver failure Glomerular filtration rate <20 ml/ min physician judgment that the patient will need mechanical ventilation in 24 hours QTc > 450 ms other indications for to colchicine, ruxolitinib, and secukinumab Chronic therapy with corticosteroids or immunosuppressive therapy Active cancer

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: Patients will be randomized 3:1:1:3 into four groups: colchicine, ruxolitinib, secukinumab, and control group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1. Colchicine<br>30 Patients with mild and severe COVID 19 Patients will get investigated therapy for ten days. Patients will be follow-up during 45 days after randomization | Drug: Colchicine<br>* 0.5mg twice a day per os during the first three days and then 0.5mg daily per os if weight < 86 kg or 0.5mg twice a day per os if weight > 85kg for seven days.<br>|
| Experimental: 2. Ruxolitinib<br>10 Patients with mild and severe COVID 19 Patients will get investigated therapy for ten days. Patients will be follow-up during 45 days after randomization | Drug: Ruxolitinib 5 MG<br>* Ruxolitinib - 5mg twice a day per os for ten days<br>|
| Experimental: 3.Secukinumab<br>10 Patients with mild and severe COVID 19 Patients will get investigated therapy singly. Patients will be follow-up during 45 days after randomization | Drug: Secukinumab 150 MG/ML Subcutaneous Solution [COSENTYX]<br>* Secukinumab - 300mg subcutaneously singly<br>|
| Active Comparator: 4.Standard treatment<br>-30 patients Patients with mild and severe COVID 19 Patients will get investigated therapy for ten days. Patients will be follow-up during 45 days after randomization | Other: standard therapy<br>* standard therapy for COVID 19<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline in clinical assessment score COVID 19 (CAS COVID 19) Frame: baseline | CAS COVID 19 measures clinical and laboratory parameters in 7 domains: respiratory rate (< 18 - 0 point; 18-22 - 1 point; 23-26 - 2 point; >26 - 3 point) body temperature (35.5 - 37.0 - 0 point; < 35.5 - 1 point; 37.1 - 38.5 - 1 point; > 38.5 - 2 point) Sp02 without support oxygen (> 93% - 0 point; 90-93% - 1 point; < 90% - 2 point) ventilation (not required - 0 point; low-flow ventilation - 1 point; Non-invasive positive pressure ventilation - 2 point; mechanical ventilation - 3 point) C-reactive protein (> 10 - 0 point; 10-59 - 1 point; 60-120 - 2 point; > 120 - 3 point) d - dimer (< 0.51 - 0 point; 0.51 - 2.0 - 1 point; 2.01 - 5.0 - 2, > 5.0 - 3 point) exposure area on lung CT (no pneumonia - 0; 1-24% - 1 point; 25-50% - 2; 51-75% - 3, > 75% - 4). Minimal number of points - 0; max - 20. Lower the score-better health | baseline, day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combine endpoint: Time to death or mechanical ventilation | time to death or mechanical ventilation | 45 days | 
| C-reactive protein | Change from baseline in C-reactive protein | baseline, day 12, day 45 | 
| D-dimer | Change from baseline in D-dimer | baseline, day 12, day 45 | 
| EuroQol Group. EQ-5D™ | Change from baseline in EQ-5D-3L™ The EQ-5D-3L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, and extreme problems. The patient is asked to indicate his/her health state by ticking the box to the most appropriate statement. This decision results into a 1-digit number, . The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'. The VAS can be used as a quantitative measure of health outcome by patient's own judgement. | baseline, day 12, day 45 | 
| exposure area on lung CT | Change from baseline in exposure area on lung CT | baseline, day 12, day 45 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID 19, colchicine, ruxolitinib, secukinumab