| CTRI Number |
CTRI/2022/08/044713 [Registered on: 17/08/2022] Trial Registered Prospectively |
| Last Modified On: |
09/08/2022 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Other |
|
Public Title of Study
|
A study to check effectiveness and safety of ES16001 in patients with Mild to Moderate Covid-19 Infection |
|
Scientific Title of Study
|
Efficacy and safety of ES16001 in patients with COVID-19: a phase II/III, multinational, randomized, parallel-group, double-blind, placebo-controlled study |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| GNC_ESE_Covid19_P2-301 Version: 2.3 Date:14 Dec 21 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Dharmesh Domadia |
| Designation |
Vice President - Global Clinical Operations |
| Affiliation |
Cliantha Research Limited |
| Address |
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India
Ahmadabad
GUJARAT
382210
India |
| Phone |
91-2717-698500 |
| Fax |
|
| Email |
ddomadia@cliantha.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Nil Desai |
| Designation |
Senior Manager Medical Services |
| Affiliation |
Cliantha Research Limited |
| Address |
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India
Ahmadabad
GUJARAT
382210
India |
| Phone |
919879732959 |
| Fax |
|
| Email |
nhdesai@cliantha.com |
|
Details of Contact Person
Public Query
|
| Name |
Mr Devesh Verma |
| Designation |
Associate Diarector-I |
| Affiliation |
Cliantha Research Limited |
| Address |
TP 86, FP 28/1,
Off S.P. Ring Road, Sarkhej,
Ahmedabad-382210,
Gujarat, India
Ahmadabad
GUJARAT
382210
India |
| Phone |
919712908404 |
| Fax |
|
| Email |
dverma@cliantha.com |
|
|
Source of Monetary or Material Support
|
| Genencell Co., Ltd.87, Jeyakgongdan 3-gil, Hyangnam-eup, Hwaseong-si, Gyeonggi-do, Korea |
|
|
Primary Sponsor
|
| Name |
Genencell Co Ltd |
| Address |
87, Jeyakgongdan 3-gil, Hyangnam-eup, Hwaseong-si, Gyeonggi-do, Korea |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| OPIS Srl |
Via Matteotti 10, 20832 Desio (MB), ltaly |
|
|
Countries of Recruitment
|
India
Republic of Korea
Russian Federation |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Badal Sahu |
Department of General Medicine Nil Ratan Sircar Medical College and Hospital |
Clinical Research Room, 1st floor- UNB building , Nil Ratan Sircar Medical college & Hospital, 138 A.J.C Bose Road, Kolkata 700014 West Bengal, India
Kolkata
WEST BENGAL |
8240184543
drbadal08@gmail.com |
| Dr Shyam Mukundan |
Lakshmi Nurshing Home |
Clincial Research Room, Ground floor, Lakshmi Nurshing Home , Palace Road, Aluva-683101, Ernakulam, Kerela, India
Ernakulam
KERALA |
9895714189
drshyammukundan@gmail.com |
| Dr Ambrish C |
Medstar Speciality Hospital |
2nd floor, Clinical research room (Documentation room), Medstar Speciality Hospital
#641/17/1/3, Kodigehalli Main Road, Sahakarnagar, Bangalore-560092, Karnataka, India
Bangalore
KARNATAKA |
9845895911
medstarclinicalreseach@gmail.com |
| Dr Palak Prajapati |
Parth Hospital |
Clinical Research Room No. 401, 402, Parth Hospital
E 405/4, 407-411 Galaxy Arcade, Galaxy Cinema Road, Ahmedabad-382330
Ahmadabad
GUJARAT |
8320299957
drpalakprajapati.cr@gmai.com |
| Dr Pravin Soni |
PCMCS PGI Yashwantrao Chavan Memorial Hospital |
2nd Floor Clincial Research Department,
General Medicine Department PCMCS PGI Yashwantrao Chavan Memorial Hospital, Sant Tukaram Nagar, Pimpri, Pune, 411018
Pune
MAHARASHTRA |
9822057511
drprainsoni182@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 5 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee Yashwantrao Chavan Memorial Hospital |
Approved |
| NRS Ethics Committee |
Approved |
| Parth Hospital Ethics Committee |
Approved |
| Speciality Hospital Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Oral Tablets of ES16001 40 mg, 80 mg, and 160 mg |
1. PHASE II (PART I )
a). 480mg group : Three 80mg ES16001 tablets twice a day.
b). 720mg group : Two 160mg ES16001 tablets + One 40mg ES16001 tablets twice a day.
C). 960mg group : Three 160mg ES16001 tablets twice a day.
D). Control Group : Three placebo tablets twice a day.
E). PHASE III (PART II)
F). Dose of ES16001 determined from the phase II.
G). Placebo |
| Comparator Agent |
Placebo |
Tablets for oral use indistinguishable from ES16001 in size, appearance, taste and smell |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Those with full understanding of the clinical study and agreeing in the participation of the clinical study voluntarily in writing, or with a deputy granted with legal authority of the relevant patient if he/she is unable to agree with the clinical study in person
2. Adults aged 18 or above at the time of screening (according to the legal age for adult in each country
3. Diagnosis of COVID-19 including a positive RT-PCR for SARS-CoV-2 within 3 days prior to administering the IMP
4. Mild or moderate patients who have the following conditions at screening and confirm at randomization:
A. Mild: Those with COVID-19 symptoms relevant to the inclusion criteria 5 without breathing difficulty or other chest radiation examination
B. Moderate: Those with disease in respiratory organs in the clinical evaluation or imaging examination (chest radiation examination, etc.) and also relevant to the following conditions:
Higher than 94% of oxygen saturation (SpO2) with room air at screening and confirm at randomization
Lower than 30 times/min respitatory frequency at screening
5. Those who happen more than one of the following symptoms within 3 days prior to the treatment of IMP and also have more than one of symptoms within a day prior to the treatment of IMP
1. Fever
2. Cough
3. Shortness of breath
4. Chills
5. Muscle pain’
6. Headache
7. Sore throat
8. Loss of smell/taste
9. Nasal congestion
10. Runny nose
11. Fatigue
12. Nausea and vomiting
13. Diarrhea
14. Phlegm
6. Those being hospitalized or scheduled in hospital or quarantined facilities
7. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use adequate methods of contraception during the study and through 90 days after the last dose of study medication. Female patients of childbearing potential are all those except patients who are surgically sterile, who have medically documented ovarian failure, or who are at least 1 year postmenopausal. Effective contraception includes an established hormonal therapy or intrauterine device for females, and the use of a barrier contraceptive (i.e. diaphragm or condoms) with spermicide
|
|
| ExclusionCriteria |
| Details |
1. Those with known or suspected hypersensitivity to ES16001 or any of its excipients
2. Those with genetic issues with galactose intolerance, lapp lactase deficiency, or glucose-galactose malasorption, etc
3. Patients with ECG evidence of a QTcF > 450 ms in men and > 470 ms in women and patients with any other risk factors for Torsades de pointes (TdP) (hypokalemia, hypomagnesemia or hypocalcemia, family history of long QT syndrome, low left ventricular ejection fraction, left ventricular hypertrophy, ischemia and slow heart rate)
4. Concomitant use of hydroxychloroquine or other drugs known to prolong QT interval throughout the study
5. Suspected active bacterial, fungal, viral, or other infection (besides COVID-19).
6. Immunosuppressor or immunomodulatory drugs within the past 3 months (excluding corticosteroids) and patients with autoimmune disease
7. Patients with one of the following severe COVID-19 signs at randomization (based on NIH classification)
SpO2<94% of oxygen saturation without oxygen supply in room air
PaO2/FiO2<300 mmHg
Respiratory frequency >30 times/min
Parenchyma infiltration> 50%
8. Patients requiring oxygen treatment (nasal prong, facial mask, and high flow oxygen) or machine respiration (oxygen by NIV or high flow, intubation and mechanical ventilation, and etc.) at randomization
9. Those requiring ECMO or CRRT treatment due to damage on multiple organs with severe illness (respiratory failure, shock, or multiple organ disorder)
10. Those with issues on kidney or liver as follows in the screening
1) ALT or AST > 5 x upper limit of normal (ULN) at screening
2)Total bilirubin that is 1.5 x upper limit of normal (ULN) at screening in the blood
3) Serum creatine > 2mg/dL (> 176.8 μmol/L) or estimated creatine clearance < 30ml/min measured or calculated by Cockroft Gault equation 11. ANC <1000/µL in the screening
11. platelet count <50,000/µL in the screening
12. Those who are pregnant or breastfeeding
13. Treatment with an investigational product within 5 times half-life or to 30 days from the screening (whichever is longer)
14. Those taking antiviral drugs, anti-inflammatory medicine, or neutralizing antibody that is known to influence the treatment of COVID-19 (refer to 7.4.2 Prohibited mendication)
Those with chronic disease that is inappropriate for the participation in clinical study judged by the investigator (Uncontrolled diabetes, chronic kidney disease, chronic liver disease, chronic lung disease, chronic cardiovascular disease, blood cancer, chemotherapeutic cancer patients, patients taking immunosuppressants, idiopathic thrombocytopenia, hyperkalemia patients, etc.)
|
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Primary Efficacy endpoint |
Approximately 5 Weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Secondary endpoint:
• Proportion of subjects requiring hospitalization due to COVID-19 or dead subjects up to the 29th day treatment |
Approximately 5 Weeks |
|
|
Target Sample Size
|
Total Sample Size="1130"
Sample Size from India="200"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2/ Phase 3 |
|
Date of First Enrollment (India)
|
20/08/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
17/05/2022 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
Nill |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This
is phase II/III, randomized, parallel-group, double-blind, placebo-controlled
study. Patients must be at least 19 years of age (or according to the legal age
for adult in each country) with confirmed mild or moderate COVID-19 tested
positive with an RT-PCR analysis of rhinopharynx samples. RT-PCR analysis of
rhinopharynx samples must be <4 days old prior to the study
enrolment.
After obtaining the consent and confirming eligibility, eligible patients will be treated
with IMP for 7 days and followed up for additional 21 days (total 29
days). Patients who are discharged from the hospital or ending the quarantine may have to visit the investigational
site on a pre-determined date for efficacy and safety follow up observation.
Final safety and efficacy data will be collected on the last study day (29t Day).
If patients are fully recovered or discharged from
the hospital prior to treatment period, all the evaluations on the day/End of
Treatment examination treatment shall be performed on the day of discharging.
Criteria of discharge from quarantined facility or
hospital will be granted when fulfilling the following conditions:
â‘ At least 10
days after the first symptom
â‘¡ No fever for 24 hours
without using an antipyretic drug
â‘¢ Other symptoms
are improved
Treatment with IMP shall be suspended in case of patients
discharged prior to the treatment completion, a follow up assessment will be performed
on Study days 10, 14 and 21. The final study visit will be
performed at the site on Day 29. During these
visits, efficacy, and safety data (adverse events) will be collected.
Should the patient’s conditions not improve during the treatment period
(until Day 7), the study treatment will be considered a failure and
discontinued. The patient will be managed as per local practice
and followed up until Day 29 for the safety
evaluation.
In case of a home quarantine or home isolated patients,
field study personnel will travel in vans or cars equipped for transportation
of NP swabs and blood samples. All study personnel and supporting staff (e.g.
drivers) will use adequate personal protection equipment (PPE) for COVID-19 in
compliance with local regulations. Vehicles will be sanitized in compliance
with local regulations.
Phase II —Dose-finding
Phase
II will be enrolled 424 patients (1:1:1:1 ratio) randomly assigned to one of
the four treatment groups as follows.
·
ES16001
480 mg /day
·
ES16001
720 mg /day
·
ES16001
960 mg /day
·
Placebo
Randomization
will be stratified depending on age and disease severity of patients.
When the phase II clinical study will be completed, the
assessment to select the dose will be performed in an unblinded manner by an
Independent Data Monitoring Committee (IDMC). An IDMC charter will be drafted
to describe the IDMC’s activities and responsibilities. dose
Phase
III
In the phase III, safety and
efficacy with the dose selected in the phase II will be compared with placebo.
In the phase III, about 706 patients will be randomized in 1:1 ratio to test
drug or placebo. Randomization will be stratified depending on the well-known
risk factors for progression and disease severity of a patient. Final Endpoints
and the sample size may be different depending on the results of the phase II. |