Efficacy and Safety of Itolizumab in COVID-19 Complications

Covid19 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04475588
• Other study ID #: ITOLI-C19-02-I-00
• Status: Completed
• Phase: Phase 2
• Start date: May 1, 2020
• Est. completion date: July 7, 2020

Study information

• Verified date: June 2021
• Source: Biocon Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized, Parallel Group, Active Controlled Trial

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 7, 2020
• Est. primary completion date: July 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Covid19
• Cytokine Release Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

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
• Best supportive care (BSC)
Best supportive care (BSC) included drugs like antivirals, antibiotics, Hydroxychloroquine, oxygen therapy, LMWH, Steroids, Vitamins and Zinc

Locations

Country	Name	City	State
India	Seth GS Medical College and KEM Hospital	Mumbai
India	Topiwala National Medical College & B. Y. L. Nair Charitable Hospital,	Mumbai
India	All India Institute Of Medical Sciences	New Delhi
India	MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital	New Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Biocon Limited

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	One-month
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%	Day 7, Day 14, Day 21 & Day 30
Primary	Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)	Number of patients needing Intubation/IMV post treatment	Day 30
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	Baseline (Day 1), Day 7, Day 14 Day 21 & Day 30
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).	Day 7, Day14, Day 21 & Day30
Primary	Reduction in Proportion of Patients- Invasive Mechanical Ventilation	Patient improved from invasive ventilation over time from baseline.	Day7, Day14, Day21 & Day 30
Primary	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
Primary	Mean Change From Baseline in Ferritin	Mean Change from Baseline in Ferritin	Day 7, Day 14, Day 21 & Day 30
Primary	Mean Change From Baseline in LDH	Mean Change from Baseline in LDH	Day 7, Day14, Day 21 and Day 30.
Primary	Mean Change From Baseline in CRP (C-reactive Protein)	Mean Change from Baseline in CRP	Day 7, Day 14, Day 21 & Day 30
Primary	Mean Change From Baseline D-Dimer		Day 7, Day 14, Day 21 & Day 30
Secondary	Mean Change From Baseline of Absolute Lymphocyte Count	Mean change From baseline in Lymphocyte count	day 7, day 14 ,day 21 & day 30
Secondary	Biomarkers (IL-6, TNF-a)	Mean values of Pre and Post 1st and 2nd dose are shown	Pre and Post 1st dose; Pre and Post 2nd dose
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)	Baseline, Day 7, Day 14, Day 21 & Day 30
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	up to Day 30