Efficacy and Safety of Itolizumab in COVID-19 Complications

Phase 2

Completed

Conditions: Acute Respiratory Distress Syndrome
Cytokine Release Syndrome
Covid19

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

Registration Number: NCT04475588

Lead Sponsor: Biocon Limited

Brief Summary: Randomized, Parallel Group, Active Controlled Trial

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

Inclusion Criteria

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

Key

Exclusion Criteria

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A - Itolizumab + BSC	Itolizumab IV infusion	-
Arm A - Itolizumab + BSC	Best supportive care (BSC)	-
Arm B - Best supportive care (BSC)	Best supportive care (BSC)	-

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in LDH	Day 7, Day14, Day 21 and Day 30.	Mean Change from Baseline in LDH
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
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%
Endo-tracheal Intubation/Invasive Mechanical Ventilation (IMV)	Day 30	Number of patients needing Intubation/IMV post treatment
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).
Reduction in Proportion of Patients- Invasive Mechanical Ventilation	Day7, Day14, Day21 & Day 30	Patient improved from invasive ventilation over time from baseline.
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.
Mean Change From Baseline in Ferritin	Day 7, Day 14, Day 21 & Day 30	Mean Change from Baseline in Ferritin
Mean Change From Baseline in CRP (C-reactive Protein)	Day 7, Day 14, Day 21 & Day 30	Mean Change from Baseline in CRP
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
Mean Change From Baseline D-Dimer	Day 7, Day 14, Day 21 & Day 30

Secondary Outcome Measures

Name	Time	Method
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
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)
Mean Change From Baseline of Absolute Lymphocyte Count	day 7, day 14 ,day 21 & day 30	Mean change From baseline in Lymphocyte count
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

Trial Locations

Locations (4): Topiwala National Medical College & B. Y. L. Nair Charitable Hospital,
🇮🇳
Mumbai, India
Seth GS Medical College and KEM 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, India