Efficacy and Safety of Itolizumab in COVID-19 Complications

A Multi-Centre, Open Label, Two Arm Randomized, Phase 2 Trial to Study the Efficacy and Safety of Itolizumab in COVID-19 Complications

Randomized, Parallel Group, Active Controlled Trial

Study Overview

• Status: Completed
• Conditions: Covid19; Acute Respiratory Distress Syndrome; Cytokine Release Syndrome
• Intervention / Treatment: Drug: Itolizumab IV infusion; Drug: Best supportive care (BSC)

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 Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Mumbai, India, 400012
    • Seth GS medical college and KEM Hospital
  • Mumbai, India, 400008
    • Topiwala National Medical College & B. Y. L. Nair Charitable Hospital,
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • New Delhi, India, 110002
    • MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Biocon Limited

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2020
• Primary Completion (ACTUAL): July 7, 2020
• Study Completion (ACTUAL): July 7, 2020

Study Registration Dates

• First Submitted: July 16, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (ACTUAL): July 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 10, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Infant, Newborn, Diseases; Shock; Lung Injury; Infant, Premature, Diseases; COVID-19; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Cytokine Release Syndrome
• Other Study ID Numbers: ITOLI-C19-02-I-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No