Efficacy and Safety of Itolizumab in COVID-19 Complications

• Sponsor: Biocon Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04475588
• Collaborator: (none)
• Enrollment: 32
• Locations: 4
• Arms: 2
• Actual Duration (Months): 2.2
• Patients Per Site: 8
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

Randomized, Parallel Group, Active Controlled Trial

Condition or Disease	Intervention/Treatment	Phase
Acute Respiratory Distress Syndrome; Cytokine Release Syndrome; Covid19	Drug: Itolizumab IV infusion; Drug: Best supportive care (BSC)	Phase 2

Detailed Description

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Centre, Open Label, Two Arm Randomized, Phase 2 Trial to Study the Efficacy and Safety of Itolizumab in COVID-19 Complications
• Actual Study Start Date: May 1, 2020
• Actual Primary Completion Date: Jul 7, 2020
• Actual Study Completion Date: Jul 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A - Itolizumab + BSC	Drug: 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); Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Active Comparator: Arm B - Best supportive care (BSC)	Drug: Best supportive care (BSC); Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc

Outcome Measures

Primary Outcome Measures

1. One-month Mortality Rate Between the Two Arms [One-month]

   1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30

2. Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2 [Day 7, Day 14, Day 21 & Day 30]

   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%

3. Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV) [Day 30]

   Number of patients needing Intubation/IMV post treatment

4. Reduction in Proportion of Patients on Non-invasive Ventilation [Baseline (Day 1), Day 7, Day 14 Day 21 & Day 30]

   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

5. Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2 [Day 7, Day14, Day 21 & Day30]

   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).

6. Reduction in Proportion of Patients- Invasive Mechanical Ventilation [Day7, Day14, Day21 & Day 30]

   Patient improved from invasive ventilation over time from baseline.

7. Reduction in Proportion of Patients-High Flow Nasal Oxygen [Day7 ,Day 14 ,Day 21, Day 30]

   Patient improved from High Flow Nasal Oxygen over time from baseline.

8. Mean Change From Baseline in Ferritin [Day 7, Day 14, Day 21 & Day 30]

   Mean Change from Baseline in Ferritin

9. Mean Change From Baseline in LDH [Day 7, Day14, Day 21 and Day 30.]

   Mean Change from Baseline in LDH

10. Mean Change From Baseline in CRP (C-reactive Protein) [Day 7, Day 14, Day 21 & Day 30]

    Mean Change from Baseline in CRP

11. Mean Change From Baseline D-Dimer [Day 7, Day 14, Day 21 & Day 30]

Secondary Outcome Measures

1. Mean Change From Baseline of Absolute Lymphocyte Count [day 7, day 14 ,day 21 & day 30]

   Mean change From baseline in Lymphocyte count

2. Biomarkers (IL-6, TNF-a) [Pre and Post 1st dose; Pre and Post 2nd dose]

   Mean values of Pre and Post 1st and 2nd dose are shown

3. 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]

   Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)

4. Number and Percentage of Patients With Radiological Response [up to Day 30]

   Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Male or female adults above 18 years (not tested in children yet)

2. Informed consent for participation in the study

3. Virological diagnosis of SARS-CoV2 infection (PCR)

4. Hospitalized due to clinical/instrumental diagnosis of COVID-19 infection

5. Oxygen saturation at rest in ambient air ≤94%

6. Patients who are in moderate to severe ARDS as defined by PaO2/Fio2 ratio of < 200

Key Exclusion Criteria:

1. Known severe allergic reactions to monoclonal antibodies

2. Active tuberculosis (TB) infection

3. History of inadequately treated tuberculosis or latent tuberculosis

4. In the opinion of the investigator,progression to death is highly probable, irrespective of the provision of treatments

5. Have received oral anti-rejection or immune-suppressive drugs within the past 6 months

6. Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor)

7. Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination

8. Patients with known history of Hepatitis B, Hepatitis C or HIV

9. Absolute Neutrophils count (ANC) <1000 / mm3

10. Platelets <50,000 / mm3

11. Absolute Lymphocyte count (ALC): <500/mm3

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Topiwala National Medical College & B. Y. L. Nair Charitable Hospital,	Mumbai		India	400008
2	Seth GS Medical College and KEM Hospital	Mumbai		India	400012
3	MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital	New Delhi		India	110002
4	All India Institute Of Medical Sciences	New Delhi		India	110029

Sponsors and Collaborators

• Biocon Limited

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jun 4, 2020
• Statistical Analysis Plan - Jun 29, 2020

More Information

Publications

None provided.

• Responsible Party: Biocon Limited
• ClinicalTrials.gov Identifier: NCT04475588
• Other Study ID Numbers: ITOLI-C19-02-I-00
• First Posted: Jul 17, 2020
• Last Update Posted: Jun 14, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Syndrome; Cytokine Release Syndrome

Study Results

Participant Flow

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Period Title: Overall Study
STARTED	22	10
COMPLETED	20	10
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)	Total
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc	Total of all reporting groups
Overall Participants	20	10	30
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.55 (12.49)	48.30 (14.62)	49.13 (13.21)
Sex: Female, Male (Count of Participants)
Female	1 5%	3 30%	4 13.3%
Male	19 95%	7 70%	26 86.7%
Race/Ethnicity, Customized (Number) [Number]
Asian	20 100%	10 100%	30 100%
Region of Enrollment (participants) [Number]
India	20 100%	10 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	One-month Mortality Rate Between the Two Arms
Description	1-month mortality is defined as the proportion of patients who met fatal outcome event by Day 30
Time Frame	One-month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Number [participants]	0 0%	3 30%

2. Primary Outcome

Title	Lung Function Assessment - Proportion of the Patients With Stable or Improved SpO2 Without Increasing FiO2
Description	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%
Time Frame	Day 7, Day 14, Day 21 & Day 30

Outcome Measure Data

Analysis Population Description

Patients improved/ weaned off O2, the observation was carried forward

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	17 85%	5 50%
Day 14	19 95%	7 70%
Day 21	20 100%	7 70%
Day 30/EOS	20 100%	7 70%

3. Primary Outcome

Title	Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)
Description	Number of patients needing Intubation/IMV post treatment
Time Frame	Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Number [participants]	0 0%	2 20%

4. Primary Outcome

Title	Reduction in Proportion of Patients on Non-invasive Ventilation
Description	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
Time Frame	Baseline (Day 1), Day 7, Day 14 Day 21 & Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Baseline (Day 1)	5 25%	4 40%
Day 7	0 0%	0 0%
Day 14	5 25%	1 10%
Day 21	5 25%	1 10%
Day 30/EOS	5 25%	1 10%

5. Primary Outcome

Title	Lung Function Assessment - Proportion of Patients With Stable PaO2 Without Increasing FiO2
Description	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).
Time Frame	Day 7, Day14, Day 21 & Day30

Outcome Measure Data

Analysis Population Description

Patients improved/ weaned off O2, the observation was carried forward.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	18 90%	6 60%
Day 14	19 95%	7 70%
Day 21	20 100%	7 70%
Day 30/EOS	20 100%	7 70%

6. Primary Outcome

Title	Reduction in Proportion of Patients- Invasive Mechanical Ventilation
Description	Patient improved from invasive ventilation over time from baseline.
Time Frame	Day7, Day14, Day21 & Day 30

Outcome Measure Data

Analysis Population Description

There were no patients on invasive mechanical ventilation at baseline

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	0	0

7. Primary Outcome

Title	Reduction in Proportion of Patients-High Flow Nasal Oxygen
Description	Patient improved from High Flow Nasal Oxygen over time from baseline.
Time Frame	Day7 ,Day 14 ,Day 21, Day 30

Outcome Measure Data

Analysis Population Description

There were no patients on High Flow Nasal Oxygen at baseline

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	0	0

8. Primary Outcome

Title	Mean Change From Baseline in Ferritin
Description	Mean Change from Baseline in Ferritin
Time Frame	Day 7, Day 14, Day 21 & Day 30

Outcome Measure Data

Analysis Population Description

only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	-117.8 (1477.0)	-87.05 (140.99)
Day 14	-713.9 (693.68)	-209.6 (177.33)
Day 21	-780.9 (630.61)	4238 (8319.0)
Day 30/EOS	-479.3 (620.95)	-234.4 (405.67)

9. Primary Outcome

Title	Mean Change From Baseline in LDH
Description	Mean Change from Baseline in LDH
Time Frame	Day 7, Day14, Day 21 and Day 30.

Outcome Measure Data

Analysis Population Description

Only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	-134 (174.67)	-44.29 (176.85)
Day 14	-195.8 (291.94)	-195.2 (119.93)
Day 21	-308.1 (202.76)	155.3 (736.47)
Day 30/EOS	-212.7 (188.48)	-97 (89.1)

10. Primary Outcome

Title	Mean Change From Baseline in CRP (C-reactive Protein)
Description	Mean Change from Baseline in CRP
Time Frame	Day 7, Day 14, Day 21 & Day 30

Outcome Measure Data

Analysis Population Description

Only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	-61.69 (81.86)	-103.6 (87.48)
Day 14	-81.65 (74.71)	-107.2 (104.66)
Day 21	-90.99 (81.97)	-127.5 (124.04)
Day 30/EOS	-103.2 (100.53)	-127.6 (59.68)

11. Primary Outcome

Title	Mean Change From Baseline D-Dimer
Time Frame	Day 7, Day 14, Day 21 & Day 30

Outcome Measure Data

Analysis Population Description

Only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	-1.43 (6.31)	2.30 (6.67)
Day 14	-0.45 (6.39)	-0.68 (0.79)
Day 21	-4.35 (6.13)	8.54 (14.40)
Day 30	-2.63 (2.43)	-0.35 (0.08)

12. Secondary Outcome

Title	Mean Change From Baseline of Absolute Lymphocyte Count
Description	Mean change From baseline in Lymphocyte count
Time Frame	day 7, day 14 ,day 21 & day 30

Outcome Measure Data

Analysis Population Description

Only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Day 7	119.95 (478.63)	45.88 (762.37)
Day 14	421.25 (569.71)	142.60 (731.94)
Day 21	701.55 (625.34)	10.00 (930.16)
Day 30/EOS	719.75 (1004.0)	85.00 (601.04)

13. Secondary Outcome

Title	Biomarkers (IL-6, TNF-a)
Description	Mean values of Pre and Post 1st and 2nd dose are shown
Time Frame	Pre and Post 1st dose; Pre and Post 2nd dose

Outcome Measure Data

Analysis Population Description

Only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	18	10
IL-6 (Pre 1st Dose)	159.09 (293.0)	162.16 (185.9)
IL-6 (Post 1st Dose)	42.98 (52.9)	211.52 (297.2)
IL-6 (Pre 2nd Dose)	311.3 (660.4)	310.4 (528.2)
IL-6 (Post 2nd Dose)	91.0 (245.6)	316.8 (373.7)
TNF-a (Pre 1st Dose)	43.64 (72.9)	11.26 (13.6)
TNF-a (Post 1st Dose)	8.87 (12.3)	39.19 (104.5)
TNF-a (Pre 2nd Dose	68.0 (109.5)	107.8 (175.3)
TNF-a (Post 2nd Dose)	50.1 (140.2)	185.0 (275.8)

14. Secondary Outcome

Title	Mean PaO2 (Partial Pressure of Oxygen) / FiO2 (Fraction of Inspired Oxygen, FiO2) Ratio (or P/F Ratio)
Description	Mean PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)
Time Frame	Baseline, Day 7, Day 14, Day 21 & Day 30

Outcome Measure Data

Analysis Population Description

Only "observed values" were used.

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Baseline/Day 1	126.57 (38.31)	114.05 (30.93)
Day 7	203.50 (95.51)	184.53 (95.51)
Day 14	283.43 (104.26)	338.40 (42.57)
Day 21	350.25 (70.36)	398.33 (24.01)
Day 30/EOS	397.67 (15.63)

15. Secondary Outcome

Title	Number and Percentage of Patients With Radiological Response
Description	Number of patients with improved X ray/CT findings as compared to baseline or returned to normal in the last assessment
Time Frame	up to Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Itolizumab + BSC	Arm B - Best Supportive Care (BSC)
Arm/Group Description	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	Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
Measure Participants	20	10
Count of Participants [Participants]	9 45%	1 10%

Adverse Events

Time Frame	30 days
Arm/Group Title	Arm A - Itolizumab + BSC		Arm B - Best Supportive Care (BSC)
Arm/Group Description	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		Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc
All Cause Mortality
	Arm A - Itolizumab + BSC		Arm B - Best Supportive Care (BSC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/22 (4.5%)		3/10 (30%)
Serious Adverse Events
	Arm A - Itolizumab + BSC		Arm B - Best Supportive Care (BSC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/22 (13.6%)		3/10 (30%)
Cardiac disorders
Pericardial effusion due to underlying hypothyroidism	1/22 (4.5%)	1	0/10 (0%)	0
Infections and infestations
Lower respiratory tract infection	0/22 (0%)	0	2/10 (20%)	2
Injury, poisoning and procedural complications
Anaphylactic reaction	1/22 (4.5%)	1	0/10 (0%)	0
Infusion related reaction	1/22 (4.5%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/22 (0%)	0	2/10 (20%)	2
Acute Respiratory Distress Syndrome	0/22 (0%)	0	2/10 (20%)	2
Other (Not Including Serious) Adverse Events
	Arm A - Itolizumab + BSC		Arm B - Best Supportive Care (BSC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/22 (81.8%)		4/10 (40%)
Cardiac disorders
Sinus tachycardia	1/22 (4.5%)	1	0/10 (0%)	0
Endocrine disorders
Hypothyroidism	1/22 (4.5%)	1	0/10 (0%)	0
Gastrointestinal disorders
Constipation	1/22 (4.5%)	1	0/10 (0%)	0
General disorders
Chills	5/22 (22.7%)	6	0/10 (0%)	0
Infections and infestations
Urinary tract infection	1/22 (4.5%)	1	0/10 (0%)	0
Fungal infection	0/22 (0%)	0	1/10 (10%)	1
Investigations
Alanine aminotransferase increased	1/22 (4.5%)	1	0/10 (0%)	0
Fibrin D dimer increased	1/22 (4.5%)	1	0/10 (0%)	0
Low density lipoprotein increased	1/22 (4.5%)	1	0/10 (0%)	0
Lymphocyte count decreased	11/22 (50%)	11	2/10 (20%)	2
Non-high-density lipoprotein cholesterol increased	1/22 (4.5%)	1	0/10 (0%)	0
Platelet count decreased	1/22 (4.5%)	1	0/10 (0%)	0
Metabolism and nutrition disorders
Hyperglycemia	4/22 (18.2%)	4	1/10 (10%)	1
Hypertriglyceridemia	2/22 (9.1%)	2	1/10 (10%)	1

Limitations/Caveats

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.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.