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

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

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)]

1. To examine lipid mediators, specifically thromboxane A2, prostaglandin D2, F2-isoprostane and/or their metabolites in convalescent subjects after treatment.
2. To assess the efficacy of Ramatroban administered during the acute illness in preventing/mitigating subsequent development of long COVID / PASC

Study Overview

• Status: Recruiting
• Conditions: COVID-19 Pneumonia; COVID-19 Respiratory Infection
• Intervention / Treatment: Drug: Ramatroban; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 324
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jayashri Krishnan, PhD; Phone Number: 9771407484; Email: Jayashri.krishnan@jssresearch.com
• Study Contact Backup: Name: Sonika Newar, PhD; Phone Number: 8800799887; Email: Sonika.newar@jssresearch.com

Study Locations

• India
  • Andhra Pradesh
    • Nellore, Andhra Pradesh, India, 524001
      • Recruiting
      • DEC Health Care
      • Contact: Manoj Kumar; Phone Number: 9700487720; Email: manojkumarmddec@gmail.com
  • Gujarat
    • Ahmedabad, Gujarat, India, 382405
      • Recruiting
      • Shakti Superspecialty Hospital
      • Contact: Devendra D Gadhadra; Phone Number: 9374643422; Email: gadhadradevendra@gmail.com
  • Maharashtra
    • Mumbai, Maharashtra, India, 400028,
      • Recruiting
      • Lifecare Hospital
      • Contact: Sandeep Gaidhani; Phone Number: 7588606598; Email: drsandeepgaidhani@gmail.com
    • Pune, Maharashtra, India, 411027
      • Recruiting
      • Sangvi Multispecialty Hospital Pvt Ltd
      • Contact: Ketan Kshirsagar; Phone Number: 9049002749; Email: drketan.sangavihospital@gmail.com
    • Pune, Maharashtra, India, 411033
      • Recruiting
      • Saikrupa Hospital
      • Contact: Rahul Sonwane; Phone Number: 9420705185; Email: dr.rahulsonawane7@gmail.com
    • Pune, Maharashtra, India, 411033
      • Recruiting
      • Spandan Hospital
      • Contact: Prakash Shende; Phone Number: 9822246881; Email: deprakashshende1979@gmil.com
    • Pune, Maharashtra, India, 411044
      • Recruiting
      • PDEA'S Ayurved Rugnalaya & Sterling Multispeciality Hospital
      • Contact: Shailesh R Adwani; Phone Number: 7776027744; Email: shaileshadwanis@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects of age 18 years and above.
2. Subject (or legally authorized representative) willing to provide informed consent and agrees to comply with planned study procedures.
3. Subjects hospitalized for SARS-COV-2 infection, having hypoxemia (SpO2: ≤ 93% on room air) and radiological evidence supporting COVID-19 pneumonia.
4. Subjects meeting 8-point WHO Ordinal Scale 5 or 6

5. 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:

   1. PCR positive in a sample collected < 72 hours prior to randomization; OR
   2. 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

6. 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.
7. 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:

1. 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

2. Subjects on invasive mechanical ventilation at screening or randomization.
3. Female subject who is pregnant, breastfeeding, or planning to become pregnant.
4. 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.
5. Subject with pre-existing clinically significant spontaneous bleeding abnormality, or any other condition as per investigator's judgment.
6. Known HIV/Hepatitis B or Hepatitis C infection.
7. Severe liver disease (ALT, AST >5 times the upper limit of normal, total bilirubin > 2 times the upper limit of normal).
8. 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.
9. Subject participated in any other clinical study using any investigational drug in the past 30 days before the screening visit.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Matching placebo will be administered orally twice a day
EXPERIMENTAL: Ramatroban 75 mg tablet	Drug: Ramatroban; 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.; Other Names: BAYu3405; IUPAC Name: 3-[(3R)-3-[(4-fluorophenyl)sulfonylamino]-1,2,3,4-tetrahydrocarbazol-9-yl]propanoic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of Serious Adverse Events (SAE)	Baseline - Day 29
Time to Clinical recovery (TTCR)	Baseline - Day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Composite endpoint of death or need for mechanical ventilation or ECMO	Baseline - Day 29
Rate of mechanical ventilation or vasopressor therapy, or ECMO	Day 29
Ventilator free days	Baseline-Day 29
Duration of hospitalization	Baseline-Day 29
Duration of ICU stay	Baseline-Day 29
Number of subjects who had thrombotic events	Within Day 29
Mortality rate	Till Day 29
Change in hemoglobin, platelets, WBC, creatinine, need for renal replacement.	Baseline- Day 29
Occurrence of serious ventricular arrhythmia	censored at hospital discharge
Total red blood cell units transfused	Baseline -Day 29
Major or Clinically Significant Non-Major Bleeding	Baseline -Day 29
Change from baseline of inflammation and coagulation markers	Baseline- Day 29

Collaborators and Investigators

• Sponsor: KARE Biosciences
• Collaborators: Biomedical Advanced Research and Development Authority; BioLink Life Sciences, Inc.; JSS Medical Research Inc.; Open Philanthropy; Charak Laboratories India Pvt. Ltd; Charak Foundation
• Investigators: Principal Investigator: Ajay Gupta, MD, KARE Biosciences; Study Director: Martin Ogletree, PhD, Points & Assists, LLC.; Study Director: Deanna J Nelson, PhD, BioLink Life Sciences, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 10, 2022
• Primary Completion (ANTICIPATED): July 1, 2024
• Study Completion (ANTICIPATED): May 31, 2026

Study Registration Dates

• First Submitted: January 23, 2023
• First Submitted That Met QC Criteria: January 28, 2023
• First Posted (ACTUAL): January 31, 2023

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 28, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19; Prostaglandin D2; Ramatroban; Thromboxane; Post-Acute Sequelae SARS-CoV-2 infection (PASC); F2-Isoprostane
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Infections; Pneumonia; Respiratory Tract Infections; Platelet Aggregation Inhibitors; Ramatroban
• Other Study ID Numbers: RAMBAN-1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No