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

COVID-19 Pneumonia Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05706454
• Other study ID #: RAMBAN-1
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 10, 2022
• Est. completion date: May 31, 2026

Study information

• Verified date: January 2023
• Source: KARE Biosciences
• Contact: Jayashri Krishnan, PhD
• Phone: 9771407484
• Email: Jayashri.krishnan[@]jssresearch.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)]

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 324
• Est. completion date: May 31, 2026
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Infections
• Pneumonia
• Respiratory Tract Infections

Intervention

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.
• Placebo
Matching placebo will be administered orally twice a day

Locations

Country	Name	City	State
India	Shakti Superspecialty Hospital	Ahmedabad	Gujarat
India	Lifecare Hospital	Mumbai	Maharashtra
India	DEC Health Care	Nellore	Andhra Pradesh
India	PDEA'S Ayurved Rugnalaya & Sterling Multispeciality Hospital	Pune	Maharashtra
India	Saikrupa Hospital	Pune	Maharashtra
India	Sangvi Multispecialty Hospital Pvt Ltd	Pune	Maharashtra
India	Spandan Hospital	Pune	Maharashtra

Sponsors (7)

Lead Sponsor	Collaborator
KARE Biosciences	BioLink Life Sciences, Inc., Biomedical Advanced Research and Development Authority, Charak Foundation, Charak Laboratories India Pvt. Ltd, JSS Medical Research Inc., Open Philanthropy

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Serious Adverse Events (SAE)		Baseline - Day 29
Primary	Time to Clinical recovery (TTCR)		Baseline - Day 15
Secondary	Composite endpoint of death or need for mechanical ventilation or ECMO		Baseline - Day 29
Secondary	Rate of mechanical ventilation or vasopressor therapy, or ECMO		Day 29
Secondary	Ventilator free days		Baseline-Day 29
Secondary	Duration of hospitalization		Baseline-Day 29
Secondary	Duration of ICU stay		Baseline-Day 29
Secondary	Number of subjects who had thrombotic events		Within Day 29
Secondary	Mortality rate		Till Day 29
Secondary	Change in hemoglobin, platelets, WBC, creatinine, need for renal replacement.		Baseline- Day 29
Secondary	Occurrence of serious ventricular arrhythmia		censored at hospital discharge
Secondary	Total red blood cell units transfused		Baseline -Day 29
Secondary	Major or Clinically Significant Non-Major Bleeding		Baseline -Day 29
Secondary	Change from baseline of inflammation and coagulation markers		Baseline- Day 29