| CTRI Number |
CTRI/2022/01/039274 [Registered on: 10/01/2022] Trial Registered Prospectively |
| Last Modified On: |
16/05/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Placebo Controlled Trial |
|
Public Title of Study
|
Safety, Pharmacokinetics, Pharmacodynamics and Efficacy study of MRG-001 on Severe and Critical SARS-CoV-2 |
|
Scientific Title of Study
|
A Phase IIa, Adaptive, Double-Blind, Randomized, Placebo-Controlled, Multi-Center Study in Hospitalized Patients Infected with Severe and Critical SARS-CoV-2 to Assess the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of MRG-001 |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| MRG2020, Version No. 2.0 Amendment 1.0 dated 16-Sep-2021 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
|
| Designation |
|
| Affiliation |
|
| Address |
|
| Phone |
|
| Fax |
|
| Email |
|
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Atul Gupta |
| Designation |
AVP, Medical and Scientific Affairs |
| Affiliation |
Navitas LifeSciences (formerly Ecron Acunova Limited) |
| Address |
Mobius Towers, SJR i-Park, EPIP, Whitefield
Bangalore
KARNATAKA
560066
India |
| Phone |
09717287654 |
| Fax |
|
| Email |
atul.gupta@navitaslifesciences.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Atul Gupta |
| Designation |
AVP, Medical and Scientific Affairs |
| Affiliation |
Navitas LifeSciences (formerly Ecron Acunova Limited) |
| Address |
Mobius Towers, SJR i-Park, EPIP, Whitefield
KARNATAKA
560066
India |
| Phone |
09717287654 |
| Fax |
|
| Email |
atul.gupta@navitaslifesciences.com |
|
|
Source of Monetary or Material Support
|
| Medregen LLC,
855 N Wolfe St., Suite 623.3 Baltimore, MD 21205, USA |
|
|
Primary Sponsor
|
| Name |
Medregen LLC |
| Address |
855 N Wolfe St., Suite 623.3
Baltimore, MD 21205, USA |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India
South Africa
United States of America |
|
Sites of Study
|
| No of Sites = 3 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr ArunKumar Radhakrishnan |
Chettinad Hospital and Research Institute |
Department of Pharmacology, Rajiv Gandhi Salai, Kelambakkam
Chennai
TAMIL NADU |
8589951229
drarunresearch2020@gmail.com |
| Dr Rajesh Vithal Gosavi |
Government Medical College & Hospital |
Professor of Medicine, Medical College Square Road
Nagpur
MAHARASHTRA |
9890225111
gosavirv@hotmail.com |
| Dr Vikas Deswal |
Medanta the Medicity |
Department of Internal Medicine and infectious diseases, Sector-38
Gurgaon
HARYANA |
9992837902
vikasdeswal1986@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 3 |
| Name of Committee |
Approval Status |
| CARE-IHEC for Faculty Research |
Approved |
| Institutional Ethics Committee, Department of Pharmacology, Government Medical College & Hospital |
Submittted/Under Review |
| Medanta Institutional Ethics Committee (MIEC) |
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 |
MRG-001 |
Plerexifor (AMD3100, 24mg/mL) and
tacrolimus (FK506, 0.5mg/mL).
Subjects enrolled will receive study drug 0.0067 mL/kg of subject body weight. Study drug will be administered through the skin of the abdominal wall SC every other day (QAD) for 13 days. |
| Comparator Agent |
Placebo |
0.9% Saline. Subjects enrolled will receive Placebo 0.0067 mL/kg of subject body weight. Placebo will be administered through the skin of the abdominal wall SC every other day (QAD) for 13 days. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1 Subject voluntarily agrees to participate in this study and is able to provide written informed consent or has a legal representative who can provide informed consent or is enrolled under International Conference on Harmonization (ICH) E6 (R2) 4.8.15 emergency use provisions as deemed necessary by the investigator (where permitted according to local law and approved nationally and by the relevant IRB) prior to performing any of the Screening Visit procedures.
2 Males and females over 18 years of age, inclusive, at the time of signing the ICF.
3 Hospitalized, with COVID-19 symptoms of respiratory illness caused by SARS-CoV-2
infection (defined as Scale 5 – 7 on the WHO 8-point ordinal scale for clinical improvement.
4 Laboratory confirmation SARS-CoV-2 by real time polymerase chain reaction in the respiratory tract (NP swab, oropharyngeal swab, tracheal aspirate, BAL) lesser or equal to 14 days prior to randomization.
5 Radiologic findings compatible with diagnosis of SARS-CoV-2 pulmonary infection
6 Women of childbearing potential must be willing and able to use at least one highly effective contraceptive method for a period from the screening visit until the end of study visit. In the context of this study, an effective method is defined as those which result in low failure rate
(i.e. less than 1 percent per year) when used consistently and correctly such as:
-Combined (estrogen and progestogen containing) hormonal contraception combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, or transdermal)
-Progestogen only hormonal contraception associated with inhibition of Ovulation (oral, injectable, implantable)
-Intrauterine device (IUD)
-Intrauterine hormone releasing system
-Vasectomized partner
-Bilateral tubal occlusion
-True abstinence. When this is in line with the preferred and usual lifestyle of the subject.
Periodic abstinence, such as calendar, ovulation, symptothermal, post ovulation methods, and withdrawal are not acceptable methods of contraception.
7 Men must be willing to use a double barrier contraception from enrollment until at 5 months
after the last dose of study drug, if not abstinent. |
|
| ExclusionCriteria |
| Details |
1 Participation in any other clinical trial of an experimental treatment for COVID-19 (remdesivir
use is permitted).
2 Significant pre existing organ dysfunction prior to randomization
-Lung: Receiving supplemental home oxygen therapy at baseline for pre-existing medical condition (other than COVID-19), as documented in medical record.
-Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record. clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction (past 3 months), heart and coronary vessel surgery (past 3 months), significant valvular heart disease, uncontrolled arterial hypertension with systolic blood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg.
-Renal: End-stage renal disease requiring renal replacement therapy or eGFR <30 mL/min
-Liver: Severe chronic liver disease defined as Child Pugh Class C
-Hematologic: Baseline platelet count <50,000/mm3
3 Concurrent treatment or prior use of drugs with actual or possible direct acting immunomodulatory activity against ARDS in COVID-19 is prohibited including JAK1/JAK2 inhibitor ruxolitinib, baricitinib and tofacitinib. However, IL-6 inhibitors such as tocilizumab, sarilumab are allowed if given >72 hours prior to first study dose. Corticosteroids are permitted throughout the study.
4 History of splenectomy or splenomegaly (spleen weighing >750 g)
5 Body mass index of >45 kg/m2 at screening
6 Underlying malignancy, or other condition, with estimated life expectancy of less than two months
7 Known family history of long QT syndrome (Torsades de Pointes) or currently taking medication that prolongs QT interval
8 Currently taking immunomodulating biologics (e.g., interferons, interleukin).
9 Extracorporeal membrane oxygenation (ECMO)
10 Use of two or more vasopressors
11 Female subjects who are pregnant or breastfeeding or planning to breastfeed at any time through 90 days after last dose of IP.
12 Received a live attenuated vaccine within 30 days prior to enrollment.
13 Positive test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, human immunodeficiency virus (HIV) antibody or Active tuberculosis or a history of inadequately treated tuberculosis.
14 Ongoing immunosuppression: solid organ transplant recipients
15 Has used an investigational drug within 30 days prior to Screening.
16 History of hypersensitivity to MRG-001 (plerixafor [AMD3100, 24 mg/mL]) and tacrolimus [FK506, 0.5 mg/mL]) or any of the excipients or to medicinal products with similar chemical structure
17 Current treatment with an anti-viral medication for COVID-19 (e.g. hydroxychloroquine, lopinavir/ritonavir), other than remdesivir
18 Unable to understand the protocol requirements, instructions and study related restrictions, the nature, scope and possible consequences of the clinical study
19 Unlikely to comply with the protocol requirements, instructions and study related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits and improbability of completing the clinical study.
20 Previously been enrolled in this clinical study.
21 Vulnerable subjects defined as individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate (e.g., persons in detention, minors and those incapable of giving consent)
22 Any condition that in the opinion of the treating physician will increase the risk for the participant. |
|
|
Method of Generating Random Sequence
|
Permuted block randomization, fixed |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the safety of MRG-001 in Severe and Critical SARS CoV-2 patients |
From Baseline to Day 60 or discharge |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
-To evaluate the efficacy of MRG-001 in Severe and Critical
SARS-CoV-2 patients.
-To evaluate the Pharmacokinetics and pharmacodynamics of MRG-001 in Severe and Critical SARS-CoV-2 patient |
From Baseline to Day 60 or discharge |
|
|
Target Sample Size
|
Total Sample Size="40"
Sample Size from India="20"
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 |
|
Date of First Enrollment (India)
|
28/01/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
14/01/2022 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="0"
Months="7"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
|
Publication Details
|
Nil |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
This study is a randomized, placebo controlled, Phase IIa study in
male and female subjects with severe and critical COVID-19.
Hospitalized subjects with severe and critical SARS-CoV-2 infection
(defined as WHO clinical improvement Scale 5 – 7) will be enrolled into the study.
The study follows an adaptive design. It will be conducted in 2 stages.
Both, Stage I and Stage II will be a double blinded study.
Stage I: 40 subjects will be randomized into MRG-001 and placebo
treatment arms at the ratio of 1:1. The attempt will be made to recruit
near equal proportion of subjects across the different countries,
however, considering the unpredictable nature of COVID-19
pandemic, the actual proportions may vary.
The study will consist of a Screening Assessment (Day -7 to 1), a
Treatment Period (Day 1 to 13 – alternate days), Follow-Up visits on
Days 14, 15, 28 and End-of-Study (EOS) (Telephonic interview if
discharged) at Day 60, unless improvement allows for discharge from
hospital without oxygen support. A dose level of 0.0067 mL/kg body weight of MRG-001 will be
planned for subjects. (Plerixafor: 0.16 mg/kg and Tacrolimus: 0.0033
mg/kg). All the subjects enrolled will receive standard treatment as
per the respective national regulations along with
IMP.
Subjects will receive doses of MRG-001 or placebo on Days 1, 3, 5,
7, 9, 11 and 13 unless improvement allows for discharge from hospital
off oxygen. Follow-up PK, PD and safety assessments will be
scheduled on Days 14 and 15 and safety assessments will be
conducted on Days 14, 28 and day 60 or at day of discharge,
whichever follows first.
Pharmacokinetic and Pharmacodynamic assessments will be
performed for 20 subjects randomized to MRG-001 treatment group
and 20 subjects in placebo group. If the subjects are discharged
earlier, the follow up, PK, PD and safety assessments will be
performed on the day of discharge. If they complete the full course of
treatment and they remain in the hospital, the follow up days would
include days 14, 15, 28 and day 60. However, if they get discharged
prior to day 14, only telephonic assessment is needed on days 14, 28
and day 60 but not on day 15.
The estimated duration of study participation (Screening through EOS
Visit) for an individual subject will be approximately two months Stage 2: This stage of the trial will be conducted based on Stage I
efficacy analysis results.
Decisions on the sample size estimation, determination of efficacy
end points will be based on the Stage I efficacy analysis results.
|