CTRI/2021/09/036317 [Registered on: 07/09/2021] Trial Registered Prospectively
Last Modified On:
31/07/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A clinical study to estimate the efficacy and safety of oral RP7214 in patients with Mild COVID-19 infection.
Scientific Title of Study
A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of oral RP7214, a DHODH inhibitor, in Patients with Symptomatic Mild SARS-CoV-2 Infection.
RP7214-2101, Version Number 4.0, Dated 05 Oct 2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Ajit Nair
Designation
Chief Development Officer
Affiliation
Incozen Therapeutics Pvt Ltd
Address
Incozen Therapeutics Pvt Ltd
450, MN Science and Technology Park, Genome Valley, Turkapally, Shameerpet Mandal
Hyderabad
Hyderabad TELANGANA 500 101 India
Phone
919820503970
Fax
Email
ajitn@incozen.com
Details of Contact Person Scientific Query
Name
Dr Jayashri Krishnan
Designation
Director - Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing, L and T Business Park,
Tower 2, 1st Floor, South Wing, L and T Business Park,
Faridabad HARYANA 121003 India
Phone
919771407484
Fax
Email
jayashri.krishnan@jssresearch.com
Details of Contact Person Public Query
Name
Dr Prajak Barde
Designation
Associate Vice President
Affiliation
Incozen Therapeutics Pvt Ltd
Address
Clinical Research and Development,
Incozen Therapeutics Pvt Ltd
450, MN Science and Technology Park,
Genome Valley, Turkapally, Shameerpet Mandal
Hyderabad
Hyderabad TELANGANA 500101 India
Phone
918418614000
Fax
Email
prajakb@incozen.com
Source of Monetary or Material Support
Incozen Therapeutics Pvt Ltd
450, MN Science and Technology Park,
Genome Valley, Turkapally, Shameerpet Mandal
Hyderabad- 500 101, India
Primary Sponsor
Name
Incozen Therapeutics Pvt Ltd
Address
450, MN Science and Technology Park,
Genome Valley, Turkapally, Shameerpet Mandal
Hyderabad- 500 101, India
BAJ RR Hospital and Research Centre,
P-14, MIDC, Phase-I,
Milap Nagar, Dombivli (East)
Maharashtra-421203, India
Thane MAHARASHTRA
9870409142
deepak.varade@gmail.com
Dr Ambanna Gowda
Citizen Hospital, Karnataka
No 14, 2nd Main Road, Dispensary Road, Kalasipalya, Bangalore-560002, India
Bangalore
Bangalore KARNATAKA
9845270377
dr.ambanagowda@gmail.com
Dr M Manoj Kumar
DEC Health Care, Andhra Pradesh
DEC Health Care, OPD Room No.: 04 16/2/219,
Pogathota, Nellore, Andhra Pradesh – 524001
Nellore ANDHRA PRADESH
8612326892
manojkumarmddec@gmail.com
Dr S S V V Narasinga Rao
Govt. Medical College & Govt. General Hospital (Old RIMSGGH)
Research Wing, 2nd Floor, Beside FM Ward, Govt.Medical College & Govt. General Hospital, Srikakulam 532001, Andhra Pradesh, India Srikakulam ANDHRA PRADESH
Department of medicine, GSVM Medical College, Swaroop Nagar, Kanpur - 208002 Kanpur Nagar UTTAR PRADESH
9415039582
sourabh.gsvmmed@gmail.com
Dr Ashpak Bangi
Jivanrekha Multispeciality Hospital
Jivanrekha Multispeciality Hospital, Sr. No.-28, Prabhu Complex, Opp. To Republic School, Dehu road, Pune - 412101 Pune MAHARASHTRA
7972700600
drashpakresearch@gmail.com
Dr Y G Sundara Raju
King George Hospital
Department of General Medicine, Rajendra Prasad ward, King George Hospital, Vishakhapatnam Visakhapatnam ANDHRA PRADESH
9573606609
drysundarrajuresearch@gmail.com
Dr Shiva Kumara
Madhu Superspeciality hospital and research Institute
Madhu Superspeciality hospital and research Institute, No. 58, Magadi Main rd., Agrahara, Dasarahali, Bangalore - 560079 Bangalore KARNATAKA
9538800755
clinicalresearchstudies23@gmail.com
Dr Manish Kumar Jain
Maharaja Agrasen Supespeciality Hospital
Maharaja Agrasen Supespeciality Hospital,Sector No 7, Central Spine, Vidyadhar Nagar, Jaipur, Rajasthan 302039 Jaipur RAJASTHAN
9414414834
doctormanishjain2@gmail.com
Dr Mohammed Mirvaz Zulfikar
Malabar Medical College
Malabar Medical College Hospital and Research Centre, Modakkallur, P. O. 673323, Atholi, Calicut, Kozhikode, Kerala. Kozhikode KERALA
4962701800
mohammedmzulfikar@gmail.com
Dr Badal Kumar Sahu
Nil Ratan Sircar Medical College and Hospital
NRS, 138 AJS Bose Road,Sealdah Kolkata- 700014 Kolkata WEST BENGAL
8240184543
drbadal08@gmail.com
Dr M Sathish Kumar
Panimalar Medical College Hospital & Research Institute
Dept. General Medicine, Ground Floor, Room No. 110, Panimalar Medical College Hospital and Research Institute, Varadharajapuram, Poonamallee Chennai,600123 Chennai TAMIL NADU
04461616161
ruzansathish@gmail.com
Dr Pravin Nagulal Soni
PCMC’S PGI Yashwantrao Chavan Memorial Hospital
2nd Floor, Department of General Medicine, YCM Hospital Rd, Sant Tukaram Nagar, Pimpri Colony, Pune, 411018 Pune MAHARASHTRA
919822057511
drpravinsoni18@gmail.com
Dr Giriraja K V
Rajalakshmi Hospital & Research Center
#21/1, Lakshmi Pura Main Road, Vidyaranya Pura, Opp. Lakshmi Pura Lake, Bangalore, Karnataka - 560097 Bangalore KARNATAKA
9986046906
drgirirajkv@gmail.com
Dr Ramshyam Agarwal
Sant Dnyaneshwar Hospital (Accord Hospital)
Spine Road Plot No. 1/1 Kendriya Vihar Road, Santa Nagar, Moshi Pradhikaran, Sector Number 4, Pimpri-Chinchwad, Maharashtra 412105
Pune
Pune MAHARASHTRA
ACE Independent Ethics Committee, Unit of Pranav Diabetes Center, Near Pranav Hospital, Ramamurthy Nagar Main Road, Banaswadi, Bangalore, Bengaluru (Bangalore) Urban Karnataka-560043, India
Institutional Ethics Committee Govt. Medical College Govt. General Hospital Balaga Srikakulam Andhra Pradesh - 532001 India
Approved
Institutional Ethics Committee Great Eastern Medical School and Hospital, Ragolu, Srikakulam, Andhra Pradesh
Approved
Institutional Ethics Committee Malabar Medical College Hospital Modakkallur Atholi Kozhikode Kozhikode Kerala - 673323 India
Approved
Institutional Ethics Committee Sai Sneh Hospital & Diagnostic Centre, Opp PMT Bus stop, Katraj, Pune 411046
Approved
Institutional Ethics Committee Yashwantrao Chavan Memorial Hospital Rd, Sant Tukaram Nagar, Pimpri Colony, Pune, 411018
Approved
Institutional Human Ethics Committee (PMCHRI-IHEC), Panimalar Medical College Hospital & Research Institute Varadharajapuram, Poonamallee Chennai,600123
Approved
Jivanrekha Institutional Ethics Committee Jivanrekha Multispecialty Hospital Sr No 28, Prabhu Complex, Opp. Republic School, Dehuroad, Pune, Maharashtra - 412101 India
Approved
Rajalakshmi Hospital Institutional Ethics Committee Rajalakshmi Hospital 21/1, Lakshmi Pura, Main Road, Opp. Lakshmi Pura Lake, Vidyaranya Pura Post, Bangalore Bengaluru (Bangalore) Urban Karnataka - 560097 India
2.Males and females of ≥ 18 years of age, at the time of signing the informed consent.
3.Patient with mild COVID-19 infection having ≥ 1 symptoms. Mild infection is defined as presence of any one of the signs and symptoms of COVID-19 such as fever, cough, sore throat, malaise, headache, muscle pain, nausea, vomiting, diarrhea, loss of taste and/or smell, without shortness of breath or hypoxia. The respiratory rate should be < 24/min and SpO2 ≥ 94% on room air. Patients should have one or more of these symptoms on the day of start of treatment.
4.Laboratory confirmed Covid-19 infection by Reverse Transcription Polymerase Chain Reaction (RT-PCR) in nasopharyngeal sample (within 72 hours prior to randomization).
5. Patient should have at least one pre-existing high-risk feature (e.g., age> 60 years, hypertension, diabetes mellitus, chronic lung disease, chronic kidney disease, liver disease, cerebrovascular disease, obesity (Body mass index (BMI) > 30.0 kg/m2), cancer) for developing severe Covid-19 illness.
6. Ability to swallow and retain oral medication.
7. Male patient who is surgically sterile, or who is willing to agree to remain completely abstinent or will agree to use barrier contraceptive measures and agrees to refrain from donating sperm during the entire study treatment period and for 3 months after the last dose of study drug.
8. Women of childbearing potential who should be willing to use a medically acceptable method of contraception as defined in Appendix B while participating in the study and for 30 days after the last dose of study drug AND must have a negative pregnancy test within 3 days prior to dosing on Day 1.
9. Willing to receive telephone calls or have videoconferences with study
team personnel.
10. Willing and able to understand the nature of this study, comply with the study procedures and follow-up procedures as per the study protocol.
ExclusionCriteria
Details
Individuals who meet any of the following criteria will be considered ineligible to participate in the study:
1. Patient with asymptomatic Covid-19 infection.
2. Patient who has experienced onset of any of Covid-19 symptoms > 5 days at the time of randomization.
3. Moderate to Severe COVID-19 infection.
-Moderate infection is defined as patients with pneumonia with no signs of severe disease. Clinical features suggestive of presence of dyspnea and/or hypoxia, fever, cough, including SpO2 ≤ 93% (range 90-93%) on room air OR respiratory rate ≥ 24 per minute.
-Severe infection is defined as patients with either severe pneumonia, acute respiratory distress syndrome, sepsis or septic shock. Clinical features suggestive of clinical signs of pneumonia plus one of the following parameters such as respiratory rate > 30 breaths/min, severe respiratory distress and SpO2 < 90% on room air; or signs of acute respiratory distress syndrome or sepsis or septic shock.
4. Subjects who are severely immunocompromised (e.g., subjects with HIV infection, subjects with solid organ transplantation or bone marrow transplantation, subjects receiving chemotherapy/ radiotherapy, subjects with primary immunodeficiency).
5. Autoimmune diseases such as multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA).
6. Patients with any bleeding disorder e.g., hemophilia and von Willebrand disease.
7. Current use of other DHODH inhibitors including teriflunomide or leflunomide.
8. Patients who are on or immediately require Covid-19 directed treatment such as antivirals (e.g., remdesivir, favipiravir), immunomodulatory treatment (e.g., tocilizumab, itolizumab, baricitinib or JAK inhibitors), convalescent plasma, oral/ intravenous steroids, or monoclonal antibodies at the time of screening.
9. Patients participating in another clinical study or use of any investigational product within 4 weeks or 5 half-lives of the drug, whichever is longer, before the date of dosing.
10. Patient with history of heart failure, Class 2 or greater using the New York Heart Association (NYHA) functional class.
11. Patients on medication that is associated with prolonged QT such as antipsychotic medications or antidepressants (e.g., citalopram, venlafaxine, and bupropion) and unable to stop the same during the trial.
12. Pregnant or lactating females.
13. Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the patient.
14. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.
15. Concurrent condition that in the investigator’s opinion would jeopardize compliance with the protocol.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of patients requiring Covid-19 related hospitalization by Day 15
15 Days
Secondary Outcome
Outcome
TimePoints
Effect of RP7214 on SARS-CoV-2 viral load and clearance in patients with mild SARS-CoV-2 infection as compared to placebo.
Effect of RP7214 on clinical symptoms
Safety of RP7214.
Immuno-modulatory effect of RP7214
15 days
Change from baseline in SARS-CoV-2 viral load
Days 3, 7 and 15
Time to symptom resolution and improvement in patients receiving RP7214 as compared to placebo.
Day 1 to Day 15
Proportion of patients demonstrating symptom resolution
Days 3, 7 and 15
Adverse Events (AEs) as assessed by laboratory tests, vital signs and physical examination.
Day 1 to 30
Change in the disease specific inflammatory markers
Days 3, 7 and 15 as compared to baseline
Target Sample Size
Total Sample Size="204" Sample Size from India="204" Final Enrollment numbers achieved (Total)= "163" Final Enrollment numbers achieved (India)="163"
A Phase 2, Randomized, Double-blind, Placebo-controlled Study of oral RP7214, a DHODH inhibitor, in Patients with Symptomatic Mild SARS-CoV-2 Infection
Ajit Nair, Prajak Barde, Kasi V Routhu, Swaroop Vakkalanka, RP7214-2101 Study Group.medRxiv 2023.02.08.23285565
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
RP7214, a novel, potent, oral, inhibitor of DHODH, has shown
preclinical evidence in inhibiting viral replication and lung inflammation.
This was a randomized, double-blind, placebo-controlled phase 2 study
in patients with symptomatic mild SARS-CoV-2 infection, having at least one
high-risk feature (e.g., hypertension, diabetes mellitus) for developing
severe Covid-19 infection. The patients received RP7214 (400 mg BID) or a
placebo for 14 days in a blinded fashion and were followed up to 30 days.
Patients also received supportive therapy (e.g., antipyretics and
antitussives for symptomatic relief) at the discretion of the investigator.
The endpoints were Covid 19 related hospitalization rate by Day 15,
SARS-CoV-2 viral load and clearance on Days 3,7 and 15, clinical symptoms
improvement by Day 15, safety, and the immuno-modulatory effect of RP7214.
A total of 163 patients were treated in the study; 82 received RP7214
and 81 received placebo. Of the total patients, 44.2% had received Covid-19
vaccine prior to the study. The symptom onset was ≤ 3 days in 22.1%. None of
the patients in the study required hospitalization. There was no difference
in the mean change of viral load between RP7214 and placebo. In the subgroup
analysis, in patients having symptom onset of ≤ 3 days, RP7214 significantly
reduced viral load on Days 3 and 7, respectively. Similarly, in
non-vaccinated patients with symptom onset of ≤ 3 days, RP7214 significantly
reduced viral load on Day 3. Overall, there was a trend towards better viral
load reduction in RP7214-treated patients with a baseline viral load of 5 log
units or higher. For all other endpoints, there was no difference between
RP7214 and placebo. Majority of the reported AEs were mild and not related
either to study treatment.
RP7214 at 400 mg BID dose level showed a statistically significant
reduction in viral load at an early stage of the disease and in
non-vaccinated patients. There was a trend towards better viral load
reduction in RP7214-treated patients with a baseline viral load of 5 log
units or higher. RP7214 showed a favorable safety profile. Further
development of RP7214 in Covid 19 in a mild symptomatic population with
co-morbidities and treated at an early stage of disease may show benefit.