Clinical trial NCT05706454: 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
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: COVID-19 Pneumonia
COVID-19 Respiratory Infection
Keywords: COVID-19
Ramatroban
Post-Acute Sequelae SARS-CoV-2 infection (PASC)
Thromboxane
Prostaglandin D2
F2-Isoprostane
Lead sponsor: KARE Biosciences
Sponsor class: INDUSTRY
Collaborators: name: JSS Medical Research Inc.
name: Biomedical Advanced Research and Development Authority
name: Open Philanthropy
name: Charak Laboratories India Pvt. Ltd
name: Charak Foundation
name: BioLink Life Sciences, Inc.
First posted: 2023-01-31
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Parallel Group, Placebo Controlled Trial
Primary purpose: TREATMENT

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 \[Follow-up Phase- Objectives- (Phase 2 \& 3)\]

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


Eligibility criteria: 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.

Primary outcomes:
measure: Rate of Serious Adverse Events (SAE)
timeFrame: Baseline - Day 29
measure: Time to Clinical recovery (TTCR)
timeFrame: Baseline - Day 15
Secondary outcomes:
measure: Composite endpoint of death or need for mechanical ventilation or ECMO
timeFrame: Baseline - Day 29
measure: Rate of mechanical ventilation or vasopressor therapy, or ECMO
timeFrame: Day 29
measure: Ventilator free days
timeFrame: Baseline-Day 29
measure: Duration of hospitalization
timeFrame: Baseline-Day 29
measure: Duration of ICU stay
timeFrame: Baseline-Day 29
measure: Number of subjects who had thrombotic events
timeFrame: Within Day 29
measure: Mortality rate
timeFrame: Till Day 29
measure: Change in hemoglobin, platelets, WBC, creatinine, need for renal replacement.
timeFrame: Baseline- Day 29
measure: Occurrence of serious ventricular arrhythmia
timeFrame: censored at hospital discharge
measure: Total red blood cell units transfused
timeFrame: Baseline -Day 29
measure: Major or Clinically Significant Non-Major Bleeding
timeFrame: Baseline -Day 29
measure: Change from baseline of inflammation and coagulation markers
timeFrame: Baseline- Day 29
Other outcomes:
Locations:
city: Nellore
country: India
facility: DEC Health Care
state: Andhra Pradesh
city: Ahmedabad
country: India
facility: Shakti Superspecialty Hospital
state: Gujarat
city: Mumbai
country: India
facility: Lifecare Hospital
state: Maharashtra
city: Pune
country: India
facility: Sangvi Multispecialty Hospital Pvt Ltd
state: Maharashtra
city: Pune
country: India
facility: Saikrupa Hospital
state: Maharashtra
city: Pune
country: India
facility: Spandan Hospital
state: Maharashtra
city: Pune
country: India
facility: PDEA'S Ayurved Rugnalaya & Sterling Multispeciality Hospital
state: Maharashtra
Study officials:
affiliation: KARE Biosciences
name: Ajay Gupta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Points & Assists, LLC.
name: Martin Ogletree, PhD
role: STUDY_DIRECTOR
affiliation: BioLink Life Sciences, Inc.
name: Deanna J Nelson, PhD
role: STUDY_DIRECTOR
References: