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Randomized, Parallel Group, Active Controlled Trial
This is a Multi-Centric, Open label, Two Arm Randomized, Phase 2 Study.
All eligible patients entering into the study will be randomized in 2:1 ratio to receive the treatment A (Best supportive care + Itolizumab) / B (Best supportive care) respectively. Each patient will undergo the treatment based on their assigned treatment for a month along with battery of tests that includes, but not limited to, cytokines and chemokine, along with recording of TLC; DLC, ANC, ALC; Platelet count; S. creatinine; T.Bilirubin; morning Vitals -pulse, BP, RR; Temperature, PaO2/FiO2, MAP, GCS.
As Itolizumab is an investigational drug, the benefit to COVID-19 patients experiencing complications such as Cytokine Release Syndrome is not known. However, findings from this study may be beneficial to the society at a large at the National and International Level.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - Itolizumab + BSC | Experimental |
| |
| Arm B - Best supportive care (BSC) | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Itolizumab IV infusion | Drug | First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks. BSC: similar to Arm B |
| Measure | Description | Time Frame |
|---|---|---|
| One-month Mortality Rate Between the Two Arms | 1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30 | One-month |
| Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2 | Stable SpO2: Defined as number of patients with absence of increase in FiO2 to maintain SpO2 ≥ 92% Improvement of SpO2: Defined as number of patients with decrease in FiO2 to maintain SpO2 > 92% | Day 7, Day 14, Day 21 & Day 30 |
| Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV) | Number of patients needing Intubation/IMV post treatment | Day 30 |
| Reduction in Proportion of Patients on Non-invasive Ventilation | Reduction in proportion of Patients on Non-invasive Ventilation: defined as number of patient improved and shifted to Face mask, Nasal cannula, non-rebreather mask or off oxygen over time | Baseline (Day 1), Day 7, Day 14 Day 21 & Day 30 |
| Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2 | Stable PaO2: Defined as number of patients with up to 10% change in PaO2/FiO2 ratio from baseline. Improvement of PaO2: Defined as number of patients with > 10% improvement in PaO2/FiO2 ratio from baseline (including patients weaned off oxygen). | Day 7, Day14, Day 21 & Day30 |
| Reduction in Proportion of Patients- Invasive Mechanical Ventilation | Patient improved from invasive ventilation over time from baseline. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline of Absolute Lymphocyte Count | Mean change From baseline in Lymphocyte count | day 7, day 14 ,day 21 & day 30 |
| Biomarkers (IL-6, TNF-a) | Mean values of Pre and Post 1st and 2nd dose are shown |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Topiwala National Medical College & B. Y. L. Nair Charitable Hospital, | Mumbai | 400008 | India | |||
| Seth GS Medical College and KEM Hospital |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A - Itolizumab + BSC | Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks. BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc |
| FG001 | Arm B - Best Supportive Care (BSC) | Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A - Itolizumab + BSC | IItolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks. BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | One-month Mortality Rate Between the Two Arms | 1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30 | Posted | Number | participants | One-month |
|
30 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A - Itolizumab + BSC | Itolizumab IV infusion Itolizumab IV infusion: First dose of 1.6 mg/kg dose iv infusion, , investigator discretion to continue with 1.6 mg/kg dose every 2 weeks or 0.8 mg/kg weekly regimen up to 4 weeks. BSC: similar to Arm B Drug: Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pericardial effusion due to underlying hypothyroidism | Cardiac disorders | Systematic Assessment | Unrelated event in Arm A |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
Due to current pandemic situation few datapoints not available for ptxs who got discharged earlier basis clinical status & bed shortage. As time to discharge was influenced by load on the hospital it was not an evaluable parameter after the trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Subramanian Loganathan | Biocon Biologics India Limited | 0802808 | 5466 | subramanian.l101@biocon.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 4, 2020 | May 17, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 29, 2020 | May 17, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012128 | Respiratory Distress Syndrome |
| D000080424 | Cytokine Release Syndrome |
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D018746 | Systemic Inflammatory Response Syndrome |
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| Best supportive care (BSC) | Drug | Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc |
|
| Day7, Day14, Day21 & Day 30 |
| Reduction in Proportion of Patients-High Flow Nasal Oxygen | Patient improved from High Flow Nasal Oxygen over time from baseline. | Day7 ,Day 14 ,Day 21, Day 30 |
| Mean Change From Baseline in Ferritin | Mean Change from Baseline in Ferritin | Day 7, Day 14, Day 21 & Day 30 |
| Mean Change From Baseline in LDH | Mean Change from Baseline in LDH | Day 7, Day14, Day 21 and Day 30. |
| Mean Change From Baseline in CRP (C-reactive Protein) | Mean Change from Baseline in CRP | Day 7, Day 14, Day 21 & Day 30 |
| Mean Change From Baseline D-Dimer | Day 7, Day 14, Day 21 & Day 30 |
| Pre and Post 1st dose; Pre and Post 2nd dose |
| Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio) | Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) | Baseline, Day 7, Day 14, Day 21 & Day 30 |
| Number and Percentage of Patients With Radiological Response | Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment | up to Day 30 |
| Mumbai |
| 400012 |
| India |
| MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital | New Delhi | 110002 | India |
| All India Institute Of Medical Sciences | New Delhi | 110029 | India |
| BG001 | Arm B - Best Supportive Care (BSC) | Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Region of Enrollment | Number | participants |
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| Primary | Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2 | Stable SpO2: Defined as number of patients with absence of increase in FiO2 to maintain SpO2 ≥ 92% Improvement of SpO2: Defined as number of patients with decrease in FiO2 to maintain SpO2 > 92% | Patients improved/ weaned off O2, the observation was carried forward | Posted | Number | participants | Day 7, Day 14, Day 21 & Day 30 |
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| Primary | Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV) | Number of patients needing Intubation/IMV post treatment | Posted | Number | participants | Day 30 |
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| Primary | Reduction in Proportion of Patients on Non-invasive Ventilation | Reduction in proportion of Patients on Non-invasive Ventilation: defined as number of patient improved and shifted to Face mask, Nasal cannula, non-rebreather mask or off oxygen over time | Posted | Number | participants | Baseline (Day 1), Day 7, Day 14 Day 21 & Day 30 |
|
|
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| Primary | Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2 | Stable PaO2: Defined as number of patients with up to 10% change in PaO2/FiO2 ratio from baseline. Improvement of PaO2: Defined as number of patients with > 10% improvement in PaO2/FiO2 ratio from baseline (including patients weaned off oxygen). | Patients improved/ weaned off O2, the observation was carried forward. | Posted | Number | participants | Day 7, Day14, Day 21 & Day30 |
|
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| Primary | Reduction in Proportion of Patients- Invasive Mechanical Ventilation | Patient improved from invasive ventilation over time from baseline. | There were no patients on invasive mechanical ventilation at baseline | Posted | Day7, Day14, Day21 & Day 30 |
|
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| Primary | Reduction in Proportion of Patients-High Flow Nasal Oxygen | Patient improved from High Flow Nasal Oxygen over time from baseline. | There were no patients on High Flow Nasal Oxygen at baseline | Posted | Day7 ,Day 14 ,Day 21, Day 30 |
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| Primary | Mean Change From Baseline in Ferritin | Mean Change from Baseline in Ferritin | only "observed values" were used. | Posted | Mean | Standard Deviation | ng/mL | Day 7, Day 14, Day 21 & Day 30 |
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| Primary | Mean Change From Baseline in LDH | Mean Change from Baseline in LDH | Only "observed values" were used. | Posted | Mean | Standard Deviation | U/L | Day 7, Day14, Day 21 and Day 30. |
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| Primary | Mean Change From Baseline in CRP (C-reactive Protein) | Mean Change from Baseline in CRP | Only "observed values" were used. | Posted | Mean | Standard Deviation | mg/L | Day 7, Day 14, Day 21 & Day 30 |
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| Primary | Mean Change From Baseline D-Dimer | Only "observed values" were used. | Posted | Mean | Standard Deviation | µg/ml | Day 7, Day 14, Day 21 & Day 30 |
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| Secondary | Mean Change From Baseline of Absolute Lymphocyte Count | Mean change From baseline in Lymphocyte count | Only "observed values" were used. | Posted | Mean | Standard Deviation | cells/mm^3 | day 7, day 14 ,day 21 & day 30 |
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| Secondary | Biomarkers (IL-6, TNF-a) | Mean values of Pre and Post 1st and 2nd dose are shown | Only "observed values" were used. | Posted | Mean | Standard Deviation | pg/ml | Pre and Post 1st dose; Pre and Post 2nd dose |
|
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| Secondary | Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio) | Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) | Only "observed values" were used. | Posted | Mean | Standard Deviation | Ratio | Baseline, Day 7, Day 14, Day 21 & Day 30 |
|
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| Secondary | Number and Percentage of Patients With Radiological Response | Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment | Posted | Count of Participants | Participants | up to Day 30 |
|
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| 1 |
| 22 |
| 3 |
| 22 |
| 18 |
| 22 |
| EG001 | Arm B - Best Supportive Care (BSC) | Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc | 3 | 10 | 3 | 10 | 4 | 10 |
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| Anaphylactic reaction | Injury, poisoning and procedural complications | Systematic Assessment | Related event in Arm A |
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| Lower respiratory tract infection | Infections and infestations | Systematic Assessment | Outcome death, in Arm B |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Outcome was death, in Arm B |
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| Infusion related reaction | Injury, poisoning and procedural complications | Systematic Assessment | Patient had Infusion Reaction, did not complete initial dose. Event resolved same day. Per protocol, patient not completing first infusion were not evaluable & were replaced. Patient recovered & was discharged 2-wks later. |
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| Acute Respiratory Distress Syndrome | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Hypothyroidism | Endocrine disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Chills | General disorders | Systematic Assessment | 1 Pt. had chills did not complete initial dose. Event resolved same day. Per protocol pt. not completing 1 dose were not evaluable & replaced. Pt had COVID19 complications, death 9 days later, deemed not related to drug. Stated in all cause mortality |
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| Urinary tract infection | Infections and infestations | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | Systematic Assessment |
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| Fibrin D dimer increased | Investigations | Systematic Assessment |
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| Low density lipoprotein increased | Investigations | Systematic Assessment |
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| Lymphocyte count decreased | Investigations | Systematic Assessment |
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| Non-high-density lipoprotein cholesterol increased | Investigations | Systematic Assessment |
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| Platelet count decreased | Investigations | Systematic Assessment |
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| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypertriglyceridemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Fungal infection | Infections and infestations | Systematic Assessment |
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| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
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