Efficacy and Safety of Itolizumab in COVID-19 Complications

NCT04475588 | Completed Phase 2 Results DMC

• 1 other identifier: ITOLI-C19-02-I-00
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 4

Brief Summary

Randomized, Parallel Group, Active Controlled Trial

Conditions

Acute Respiratory Distress Syndrome; Cytokine Release Syndrome; Covid19

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (4)

• Mean Change From Baseline of Absolute Lymphocyte Count

  day 7, day 14 ,day 21 & day 30

• Biomarkers (IL-6, TNF-a)

  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)

  Baseline, Day 7, Day 14, Day 21 & Day 30

• Number and Percentage of Patients With Radiological Response

  up to Day 30

Study Arms (2)

Arm A - Itolizumab + BSC

EXPERIMENTAL

Drug: Itolizumab IV infusion; Drug: Best supportive care (BSC)

Arm B - Best supportive care (BSC)

ACTIVE COMPARATOR

Drug: Best supportive care (BSC)

Interventions

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

Arm A - Itolizumab + BSC

Best supportive care (BSC) DRUG

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

Arm A - Itolizumab + BSC; Arm B - Best supportive care (BSC)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adults above 18 years (not tested in children yet)
• Informed consent for participation in the study
• Virological diagnosis of SARS-CoV2 infection (PCR)
• Hospitalized due to clinical/instrumental diagnosis of COVID-19 infection
• Oxygen saturation at rest in ambient air ≤94%
• Patients who are in moderate to severe ARDS as defined by PaO2/Fio2 ratio of \< 200

You may not qualify if:

• Known severe allergic reactions to monoclonal antibodies
• Active tuberculosis (TB) infection
• History of inadequately treated tuberculosis or latent tuberculosis
• In the opinion of the investigator,progression to death is highly probable, irrespective of the provision of treatments
• Have received oral anti-rejection or immune-suppressive drugs within the past 6 months
• Participating in other drug clinical trials (participation in COVID-19 anti-viral trials may be permitted if approved by Medical Monitor)
• Pregnant or breastfeeding, or positive pregnancy test in a pre-dose examination
• Patients with known history of Hepatitis B, Hepatitis C or HIV
• Absolute Neutrophils count (ANC) \<1000 / mm3
• Platelets \<50,000 / mm3
• Absolute Lymphocyte count (ALC): \<500/mm3

Sponsors & Collaborators

• Biocon Limited: lead

Study Sites (4)

Topiwala National Medical College & B. Y. L. Nair Charitable Hospital,

Mumbai, 400008, India

Location

Seth GS Medical College and KEM Hospital

Mumbai, 400012, India

Location

MAMC medical college and Lok Nayak Jai Prakash Narayan Hospital hospital

New Delhi, 110002, India

Location

All India Institute Of Medical Sciences

New Delhi, 110029, India

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; Cytokine Release Syndrome; COVID-19

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Limitations and 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.

Results Point of Contact

• Title: Dr. Subramanian Loganathan
• Organization: Biocon Biologics India Limited

subramanian.l101@biocon.com

0802808

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2020
• First Posted: July 17, 2020
• Study Start: May 1, 2020
• Primary Completion: July 7, 2020
• Study Completion: July 7, 2020
• Last Updated: June 14, 2021
• Results First Posted: May 20, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (4)