CTRI/2022/12/048284 [Registered on: 20/12/2022] Trial Registered Prospectively
Last Modified On:
27/12/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A prospective clinical
study to evaluate the efficacy and safety of 101-PGC-005 for moderate COrona VIrus Disease(Covid-19).
Scientific Title of Study
A prospective, randomized, comparative, multi-centric, adaptive design clinical
study to evaluate efficacy, safety and tolerability of 101-PGC-005 (‘005) for
the treatment of moderate COrona VIrus Disease (Covid-19) disease patients.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
ICS/LAX/2022-005, Version 1.0 Date 01-Jun-2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
101-PGC-005 20 mg inj. once daily for 3 days + SOC
Comparator Agent
Dexamethasone
Dexamethasone 6mg inj once daily for max. 10 days + SOC
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1.Patients willing and able to provide voluntary written informed consent and to follow the protocol specific requirements.
2. Male or female patients of age 18 to 65 years (both inclusive).
3. Patients with ‘moderate’ COVID-19 disease severity, as defined by Comprehensive Guidelines for Management of COVID-19 patients, Directorate General of Health Services, MoHFW, GOI; AND having any of the following symptoms and signs prior
to randomization:
a. Fever, cough, with or without sore throat/throat irritation, body ache/headache,
malaise/weakness, diarrhoea or gastrointestinal upset, with or without anorexia/nausea/vomiting, with or without loss of smell and/or taste, shortness of breath/breathlessness and difficulty in breathing
b. Respiratory rate of >24 to <30 breaths/min,
c. SpO2: 90 – 93% on room air
4. Patients with positive RT-PCR test for SARS-CoV-2 in nasopharyngeal or oropharyngeal swabs (sample collected within 7 days prior to randomization)
5. Elevated CRP, ESR or Ferritin levels
6. In case of female patients of child-bearing potential, a negative urine pregnancy test prior to beginning the therapy.
7. Willing to sign voluntary informed consent for participation in the study and willing to adhere to all protocol procedures. In case the subject is unable to provide informed consent than the same should be obtained from legally acceptable representative (LAR)
ExclusionCriteria
Details
1. Patients with ‘mild’ or ‘severe’ COVID-19 disease severity, as defined by latest Comprehensive Guidelines for Management of COVID-19 patients, Directorate General of Health Services, MoHFW, GOI at the time of randomization. This includes any one or more of the following
a. Peripheral Blood oxygen saturation ≥94% or <90%
b. Respiratory Rate or <24 or ≥30 breaths per minute
2. First positive RT-PCR more than 7 days prior to treatment administration
3. Patients with evidence of other serious infectious, malignant, autoimmune, kidney, hepatic, cardiovascular or other systemic disease and/or laboratory abnormality, which, in the opinion of the investigator, prevent the patient from participating in the study
4. Subjects with Chronic liver disease (Child Pugh class B or C) and chronic renal disease (GFR<30ml/min).
5. Renal dysfunction [Serum Creatinine > 2.5 times of ULN or calculated creatinine clearance < 30ml/min], Liver Dysfunction [Total Bilirubin > 3times ULN & AST/ALT > 5times ULN].
6. Chronic systemic glucocorticoid treatment or any immunosuppressive treatment
7. History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
8. Pregnant and Lactating patients.
9. Patients who require IL-6 inhibitors for management of inflammation at the time of study entry.
10. Subject has a psychiatric disease that is not well controlled where controlled is defined as: stable on a regimen for more than one year.
11. Hospital discharge is anticipated in ≤ 24 hours or anticipated transfer to another hospital which is not a study site within 72 hours.
12. Patients that are currently or have participated in such studies participating in other clinical studies with investigational drug, biological agent or device within 1 month or within 5 half-lives (of the drug/biologic) prior to randomization (whichever is longer).
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Sequentially numbered, sealed, opaque envelopes
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Clinical improvement or shift in WHO 11-point ordinal scale rating.
Time-points: Baseline through Day 10, Day 14 and Day 28
Secondary Outcome
Outcome
TimePoints
Improvement in COVID-19 Symptoms such as Fever, Heart Rate and Oxygen
Saturation
Time-points: Baseline through Day 10, Day 14 and Day 28
Improvement biochemical inflammatory markers such as CRP,Neutrophil-Lymphocyte(N/L) ratio, D-Dimer, Sr. Ferritin, IL-6, TNF-α
Time points: Baseline, Day 14, Day 28
Requirement of auxiliary oxygen therapy
Time frame: 28 Days
Discharge Rate from hospital
Time frame: 28 Days
Rate of ICU Admission / Mechanical Ventilation
Time frame: 28 Days
Time to respiratory viral clearance
Time points: 3, 7, 10, 14 Days
Improvement in lung injury on Chest HRCT
Time frame: Baseline, 14, 28 days
All-cause mortality
Time frame: 28 days
Vital Signs, Physical Examination & other safety evaluation (ECG) analysis
Time frame: 28 days
Changes in Lab. Safety Values for CBC, LFT, KFT, FPG
Changes in Lab. Safety Values for CBC, LFT, KFT, FPG
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Coronavirus disease 2019 (COVID-19) is defined as illness caused by a novel coronavirus
now called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; formerly
called 2019-nCoV), which was first identified amid an outbreak of respiratory illness
cases in Wuhan City, Hubei Province, China. It was initially reported to the WHO on
December 31, 2019. On January 30, 2020, the WHO declared the COVID-19 outbreak a
global health emergency.
COVID-19 disease does not have any approved treatment. However, an array of drugs
approved for other indications, as well as multiple investigational agents, are being studied
for the treatment of COVID-19 in several hundred clinical trials around the globe. The recent RECOVERY Trial demonstrated the success of
dexamethasone in treating late stage COVID-19 patients. However, use of
Dexamethasone increased mortality in early stage of the disease and due to limitations of
use of free dexamethasone because of the dose and duration that is insufficient to
properly treat COVID-19 patients. As majority of the cells have glucocorticoid receptors
to which the dexamethasone binds, highly toxic dose would be needed to effectively treat . COVID-19 disease which would result in increase in mortality and this dose may
modulate T cells and other immune cells, resulting in decreased natural immunity. 101-
PGC-005 (‘005), which is a prodrug of dexamethasone will address the many safety issues limiting this most powerful anti-inflammatory agent.
This is a prospective, randomized, comparative, multi-centric, adaptive design clinical
study to evaluate efficacy, safety and tolerability of 101-PGC-005 (‘005) when used
alongside Standard of Care (SOC) for the treatment of hospitalized patients with
coronavirus disease (COVID-19).