A Clinical Trial of Mycobacterium w in Critically Ill COVID 19 Patients

Study Overview
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Brief Summary
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The trial is randomized, blinded, two arms, active comparator controlled, clinical trial to evaluate the safety and efficacy of Mycobacterium w in combination with standard care as per hospital practice versus standard care alone in critically ill adult patients suffering from COVID-19 infection.

Detailed Description
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In this study, Eligible patients will be enrolled after due consent and will be randomized in balance to receive either test drug (along with the standard of care) or Placebo (along with the standard of care). The enrolled patients will be monitored for any adverse events (AEs) or serious adverse events (SAEs) throughout the study period. All patients will continue to receive standard therapy till considered requisite by the treating physician. In addition to the standard care for COVID-19, patients randomized to test arm will receive single daily dose of 0.3 ml of Mw, intradermal, for 3 consecutive days while patients randomized to control arm will receive single daily dose of 0.3 ml of Placebo, intradermal, for 3 consecutive days. Study duration for each patient will be upto 28 days post-randomization.

Official Title
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A Clinical Trial to Evaluate the Safety and Efficacy of Mycobacterium W in Critically Ill Patients Suffering From COVID 19 Infection

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Suspension of heat killed (autoclaved) Mycobacterium w
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Critically ill patients infected with COVID-19 (clinical/confirmed) Patient aged 18 years or more of either gender Illness of any duration with respiratory rate ≥25 breaths/minute, and at least one of the following: Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), or or SpO2 ≤94% on room air, or Requiring mechanical ventilation and/or supplemental oxygen Female patients of childbearing potential must have a negative pregnancy test within 14 days prior to first dose of study medication. Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedure. Exclusion Criteria: Pregnant or nursing female. Patients with history of allergy, hypersensitivity, or any serious reaction to study medication Patients with a concomitant medical condition, whose participation, in the opinion of the investigator, may create an unacceptable additional risk. Patient previously enrolled into this study. Patient participating or having participated in a clinical trial with another investigational drug within the last 28 days except for investigational drugs against cancer, leukaemia or HIV. Patients with a life expectancy judged to be less than five days ALT/AST > 5 times the upper limit of normal Stage 4 severe chronic kidney disease or requiring dialysis (i.e. eGFR < 30) Patients not likely to complete the trial as per judgment of the investigator.

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: Randomized, blinded, two arms, active comparator controlled, clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Suspension of Mw + Standard therapy of COVID-19<br>0.3 ml (0.1ml x 3 Injection) of intradermal Mw for 3 consecutive days + Standard therapy of COVID-19 | Drug: Suspension of heat killed (autoclaved) Mycobacterium w<br>* Patients will be randomized to receive either Mycobacterium w in combination with standard care as per hospital practice or standard care alone in COVID-19 as per hospital practice.<br>* Other names: Standard care of treatment for COVID-19 as per hospital practice;|
| Placebo Comparator: Standard therapy of COVID-19<br>0.3 ml (0.1ml x 3 Injection) of Placebo intra-dermal for 3 consecutive days | Drug: Placebo<br>* All patients will continue to receive standard therapy as per hospital practice till considered requisite by the treating physician<br>* Other names: Standard care of treatment for COVID-19 as per hospital practice;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-category ordinal scale that ranges from 1 (not hospitalized with resumption of normal activities) to 7 (death) | To study the effect of Mw on recovery of organ function as assessed by Ordinal scale | Change in Ordinal scale from baseline to day 3, day 7, day 14, day 21 and day 28 and day of transfer from ICU, if discharged earlier than 28 days post-randomization. | 
| Sequential Organ Failure Assessment (SOFA) scores | To study the effect of Mw on recovery of organ function as assessed by Sequential Organ Failure Assessment (SOFA) which is based on six different scores, one for each of the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems each scored from 0 to 4 with an increasing score reflecting worsening organ dysfunction | Change in SOFA score from baseline to day 3, day 7, day 14, day 21 and day 28 and day of transfer from ICU, if discharged earlier than 28 days post-randomization. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AE / SAE or event of clinical significance | Any AE / SAE or event of clinical significance observed during the study. | Till day 28 | 
| SARS-CoV-2 detectable in nasal or oropharyngeal (OP) sample | Percent of subjects with SARS-CoV-2 detectable in nasal or oropharyngeal (OP) sample. | At days 3, 7, 14, 21, and 28 | 
| ICU length of stay | ICU length of stay | Till day 28 | 
| Duration of mechanical ventilation | Duration of mechanical ventilation | Till day 28 | 
| Duration of hospitalization | Duration of hospitalization | Till day 28 | 
| Clinical improvement | Percentage of subjects having clinical improvement defined as two-point improvement on a seven category ordinal scale. | From baseline to day 14 & Day 28 | 
| Time (in days) from treatment initiation to death | Time (in days) from treatment initiation to death. | Till day 28 | 
| All-cause mortality | All-cause mortality | Till day 28 |