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Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia

Primary Purpose

COVID-19 Pneumonia, COVID-19 Respiratory Infection

Status
Recruiting
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Ramatroban
Placebo
Sponsored by
KARE Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 Pneumonia focused on measuring COVID-19, Ramatroban, Post-Acute Sequelae SARS-CoV-2 infection (PASC), Thromboxane, Prostaglandin D2, F2-Isoprostane

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female subjects of age 18 years and above. Subject (or legally authorized representative) willing to provide informed consent and agrees to comply with planned study procedures. Subjects hospitalized for SARS-COV-2 infection, having hypoxemia (SpO2: ≤ 93% on room air) and radiological evidence supporting COVID-19 pneumonia. Subjects meeting 8-point WHO Ordinal Scale 5 or 6 Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen, as documented by either of the following: PCR positive in a sample collected < 72 hours prior to randomization; OR PCR positive in sample collected ≥ 72 hours but < 10 days prior to randomization AND non-improving or progressive disease suggestive of ongoing SARS-CoV-2 infection. i. Note: In case if the subject is not having previous reports, a quantitative analysis will be performed Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 36. Agrees to not participate in another clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through-out the study period Exclusion Criteria: Subject with immediately life-threatening SARS-CoV-2 infection. -Life-threatening disease is defined as respiratory failure, septic shock, and/or multiple organ dysfunction or failure Subjects on invasive mechanical ventilation at screening or randomization. Female subject who is pregnant, breastfeeding, or planning to become pregnant. Subject having other clinically significant gastrointestinal (GI) disease/ GI surgery that in the opinion of the investigator would interfere with the absorption of Ramatroban or subject is unable to swallow oral medications. Subject with pre-existing clinically significant spontaneous bleeding abnormality, or any other condition as per investigator's judgment. Known HIV/Hepatitis B or Hepatitis C infection. Severe liver disease (ALT, AST >5 times the upper limit of normal, total bilirubin > 2 times the upper limit of normal). Subject with known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis. Subject participated in any other clinical study using any investigational drug in the past 30 days before the screening visit. Subject with a history of life-threatening neoplasms within 5 years prior to the screening visit, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin.

Sites / Locations

  • DEC Health CareRecruiting
  • Shakti Superspecialty HospitalRecruiting
  • Lifecare HospitalRecruiting
  • Sangvi Multispecialty Hospital Pvt LtdRecruiting
  • Saikrupa HospitalRecruiting
  • Spandan HospitalRecruiting
  • PDEA'S Ayurved Rugnalaya & Sterling Multispeciality HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ramatroban 75 mg tablet

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Rate of Serious Adverse Events (SAE)
Time to Clinical recovery (TTCR)

Secondary Outcome Measures

Composite endpoint of death or need for mechanical ventilation or ECMO
Rate of mechanical ventilation or vasopressor therapy, or ECMO
Ventilator free days
Duration of hospitalization
Duration of ICU stay
Number of subjects who had thrombotic events
Mortality rate
Change in hemoglobin, platelets, WBC, creatinine, need for renal replacement.
Occurrence of serious ventricular arrhythmia
Total red blood cell units transfused
Major or Clinically Significant Non-Major Bleeding
Change from baseline of inflammation and coagulation markers

Full Information

First Posted
January 23, 2023
Last Updated
January 28, 2023
Sponsor
KARE Biosciences
Collaborators
JSS Medical Research Inc., Biomedical Advanced Research and Development Authority, Open Philanthropy, Charak Laboratories India Pvt. Ltd, Charak Foundation, BioLink Life Sciences, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05706454
Brief Title
Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia
Official Title
Randomized, Double-Blind, Placebo-Controlled, Parallel-Design, Multi- Centre, Adaptive Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For SARS-CoV-2 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2022 (Actual)
Primary Completion Date
July 1, 2024 (Anticipated)
Study Completion Date
May 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
KARE Biosciences
Collaborators
JSS Medical Research Inc., Biomedical Advanced Research and Development Authority, Open Philanthropy, Charak Laboratories India Pvt. Ltd, Charak Foundation, BioLink Life Sciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Phase II/Phase III study to evaluate the safety and efficacy of Ramatroban 75 mg tablet against Placebo in subjects hospitalized for pneumonia due to SARS-CoV-2 infection. Approximately 324 eligible subjects will be randomized in a 1:1 ratio to one of the two treatment groups. Group I: Ramatroban 75 mg tablet + Standard of care; Group II: Placebo + Standard of care. Phase 2 Primary Objective: To evaluate the safety of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Secondary Objective: To assess the efficacy of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Phase 3 Primary Objective: To evaluate the efficacy of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Secondary Objective: To evaluate the safety of Ramatroban 75 mg tablet with the standard of care against Placebo with the standard of care in COVID-19 hospitalized subjects. Long COVID [Follow-up Phase- Objectives- (Phase 2 & 3)] To examine lipid mediators, specifically thromboxane A2, prostaglandin D2, F2-isoprostane and/or their metabolites in convalescent subjects after treatment. To assess the efficacy of Ramatroban administered during the acute illness in preventing/mitigating subsequent development of long COVID / PASC

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Pneumonia, COVID-19 Respiratory Infection
Keywords
COVID-19, Ramatroban, Post-Acute Sequelae SARS-CoV-2 infection (PASC), Thromboxane, Prostaglandin D2, F2-Isoprostane

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Parallel Group, Placebo Controlled Trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participant, Investigator and Outcome Assessor Blinded Method of concealment: Pharmacy-controlled Randomization
Allocation
Randomized
Enrollment
324 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ramatroban 75 mg tablet
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Ramatroban
Other Intervention Name(s)
BAYu3405, IUPAC Name: 3-[(3R)-3-[(4-fluorophenyl)sulfonylamino]-1,2,3,4-tetrahydrocarbazol-9-yl]propanoic acid
Intervention Description
Route of Administration: Oral Dose: 75 mg; Frequency: Twice daily; Total duration of intervention: 28 days. Subjects will be evaluated over a study period of approximately 365 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be administered orally twice a day
Primary Outcome Measure Information:
Title
Rate of Serious Adverse Events (SAE)
Time Frame
Baseline - Day 29
Title
Time to Clinical recovery (TTCR)
Time Frame
Baseline - Day 15
Secondary Outcome Measure Information:
Title
Composite endpoint of death or need for mechanical ventilation or ECMO
Time Frame
Baseline - Day 29
Title
Rate of mechanical ventilation or vasopressor therapy, or ECMO
Time Frame
Day 29
Title
Ventilator free days
Time Frame
Baseline-Day 29
Title
Duration of hospitalization
Time Frame
Baseline-Day 29
Title
Duration of ICU stay
Time Frame
Baseline-Day 29
Title
Number of subjects who had thrombotic events
Time Frame
Within Day 29
Title
Mortality rate
Time Frame
Till Day 29
Title
Change in hemoglobin, platelets, WBC, creatinine, need for renal replacement.
Time Frame
Baseline- Day 29
Title
Occurrence of serious ventricular arrhythmia
Time Frame
censored at hospital discharge
Title
Total red blood cell units transfused
Time Frame
Baseline -Day 29
Title
Major or Clinically Significant Non-Major Bleeding
Time Frame
Baseline -Day 29
Title
Change from baseline of inflammation and coagulation markers
Time Frame
Baseline- Day 29

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects of age 18 years and above. Subject (or legally authorized representative) willing to provide informed consent and agrees to comply with planned study procedures. Subjects hospitalized for SARS-COV-2 infection, having hypoxemia (SpO2: ≤ 93% on room air) and radiological evidence supporting COVID-19 pneumonia. Subjects meeting 8-point WHO Ordinal Scale 5 or 6 Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen, as documented by either of the following: PCR positive in a sample collected < 72 hours prior to randomization; OR PCR positive in sample collected ≥ 72 hours but < 10 days prior to randomization AND non-improving or progressive disease suggestive of ongoing SARS-CoV-2 infection. i. Note: In case if the subject is not having previous reports, a quantitative analysis will be performed Women of childbearing potential must agree to either abstinence or use at least one primary form of contraception not including hormonal contraception from the time of screening through Day 36. Agrees to not participate in another clinical trial (both pharmacologic and other types of interventions) for the treatment of COVID-19 through-out the study period Exclusion Criteria: Subject with immediately life-threatening SARS-CoV-2 infection. -Life-threatening disease is defined as respiratory failure, septic shock, and/or multiple organ dysfunction or failure Subjects on invasive mechanical ventilation at screening or randomization. Female subject who is pregnant, breastfeeding, or planning to become pregnant. Subject having other clinically significant gastrointestinal (GI) disease/ GI surgery that in the opinion of the investigator would interfere with the absorption of Ramatroban or subject is unable to swallow oral medications. Subject with pre-existing clinically significant spontaneous bleeding abnormality, or any other condition as per investigator's judgment. Known HIV/Hepatitis B or Hepatitis C infection. Severe liver disease (ALT, AST >5 times the upper limit of normal, total bilirubin > 2 times the upper limit of normal). Subject with known severe renal impairment (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) or receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis. Subject participated in any other clinical study using any investigational drug in the past 30 days before the screening visit. Subject with a history of life-threatening neoplasms within 5 years prior to the screening visit, other than carcinoma in situ of the cervix or basal cell carcinoma of the skin.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jayashri Krishnan, PhD
Phone
9771407484
Email
Jayashri.krishnan@jssresearch.com
First Name & Middle Initial & Last Name or Official Title & Degree
Sonika Newar, PhD
Phone
8800799887
Email
Sonika.newar@jssresearch.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ajay Gupta, MD
Organizational Affiliation
KARE Biosciences
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Martin Ogletree, PhD
Organizational Affiliation
Points & Assists, LLC.
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Deanna J Nelson, PhD
Organizational Affiliation
BioLink Life Sciences, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
DEC Health Care
City
Nellore
State/Province
Andhra Pradesh
ZIP/Postal Code
524001
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manoj Kumar
Phone
9700487720
Email
manojkumarmddec@gmail.com
Facility Name
Shakti Superspecialty Hospital
City
Ahmedabad
State/Province
Gujarat
ZIP/Postal Code
382405
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Devendra D Gadhadra
Phone
9374643422
Email
gadhadradevendra@gmail.com
Facility Name
Lifecare Hospital
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400028,
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sandeep Gaidhani
Phone
7588606598
Email
drsandeepgaidhani@gmail.com
Facility Name
Sangvi Multispecialty Hospital Pvt Ltd
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411027
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ketan Kshirsagar
Phone
9049002749
Email
drketan.sangavihospital@gmail.com
Facility Name
Saikrupa Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411033
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rahul Sonwane
Phone
9420705185
Email
dr.rahulsonawane7@gmail.com
Facility Name
Spandan Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411033
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Prakash Shende
Phone
9822246881
Email
deprakashshende1979@gmil.com
Facility Name
PDEA'S Ayurved Rugnalaya & Sterling Multispeciality Hospital
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411044
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shailesh R Adwani
Phone
7776027744
Email
shaileshadwanis@gmail.com

12. IPD Sharing Statement

Learn more about this trial

Phase 2/Phase 3 Study To Evaluate The Efficacy And Safety Of Ramatroban Along With The Standard Of Care In Subjects Hospitalized For COVID Pneumonia

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