A Clinical Study to Evaluate the Efficacy and Safety of Ramatroban along with the standard of care in Hospitalized Subjects with SARS-CoV-2 Infection.
Scientific Title of Study
A Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Multi-Centre, Adaptive Phase II/Phase III Study to Evaluate the Efficacy and Safety of Ramatroban along with the standard of care in Hospitalized Subjects with SARS-CoV-2 Infection.
Trial Acronym
RAMBAN-1
Secondary IDs if Any
Secondary ID
Identifier
RAMBAN-1, Version-1.0 dated 11 Jun 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Jayashri Krishnan
Designation
Director Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing, L & T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawaja Metro Station, Faridabad -121003, Haryana, India.
Faridabad HARYANA 121003 India
Phone
9771407484
Fax
0129-6613520
Email
Jayashri.krishnan@jssresearch.com
Details of Contact Person Scientific Query
Name
Dr Sonika Newar
Designation
General Manager – Medical Monitoring and Safety
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing, L & T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawaja Metro Station, Faridabad -121003, Haryana, India.
Faridabad HARYANA 121003 India
Phone
8800799887
Fax
0129-6613520
Email
Sonika.newar@jssresearch.com
Details of Contact Person Public Query
Name
Dr Jayashri Krishnan
Designation
Director Operations
Affiliation
JSS Medical Research Asia Pacific Private Limited
Address
Tower 2, 1st Floor, South Wing, L & T Business Park, Plot no 12/4, Sector 27 D, Delhi Mathura Road, Near Sarai Khawaja Metro Station, Faridabad -121003, Haryana, India.
Faridabad HARYANA 121003 India
Phone
9771407484
Fax
0129-6613520
Email
Jayashri.krishnan@jssresearch.com
Source of Monetary or Material Support
ASPR - BARDA
US Dept of Health and Human Services
Biomedical Advanced Research and Development Authority
200 Independence Ave., SW,
Washington, DC 20201
Open Philanthropy, 182 Howard Street #225, San Francisco, CA 94105
Primary Sponsor
Name
Charak Laboratories Pvt. Ltd
Address
Trade House,14/3, South Tukoganj, Near Hotel Surya, Dhakkan Wala Kuan, Indore-452001, Madhya Pradesh, India.
Type of Sponsor
Other [Chemical Manufacturing Company]
Details of Secondary Sponsor
Name
Address
JSS Medical Research Asia Pacific Private Limited
Tower 2, 1st Floor, South Wing, L&T Business Park, Plot no 12/4, Sector 27D, Delhi Mathura Road, Near Sarai Khwaja Metro Station, Faridabad-121003, Haryana, India
Sant Savta Marg, Byculla (East), Mumbai-400027 Mumbai MAHARASHTRA
9833143662
sonamsolanki@gmail.com
Dr Ajay Bulle
Meditrina Institute of Medical Sciences
1st Floor, OPD-01, 278, Central Bazaar Road, Ramdaspeth, Nagpur, 440010, Maharashtra, India. Nagpur MAHARASHTRA
9921981109
ajaybulle@yahoo.com
Dr Pravin Nagulal Soni
PCMC’S PGI Yashwantrao Chavan Memorial Hospital
2nd Floor, General Medicine Department, PCMCS PGI Yashwantrao Chavan Memorial Hospital, Sant Tukaram Nagar, Pimpri, Pune-411018, Maharashtra, India. Pune MAHARASHTRA
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
Matching placebo will be administered orally twice a day
Intervention
Ramatroban 75 mg tablet
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
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
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:
a. PCR positive in a sample collected < 72 hours prior to randomization;
OR
b. 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
ExclusionCriteria
Details
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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pharmacy-controlled Randomization
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
Phase II
1. Rate of Serious Adverse Events (SAE)
Phase III
1. Time to Clinical recovery (TTCR)
Phase II
1. Baseline - Day 29
Phase III
1. Baseline - Day 15
Secondary Outcome
Outcome
TimePoints
Phase II & III
1. Composite endpoint of death or need for mechanical ventilation or ECMO
2. Rate of mechanical ventilation or vasopressor therapy, or ECMO
3. Ventilator free days
4. Duration of hospitalization & ICU stay
5. Number of subjects who had thrombotic events
6. Mortality rate
7. Change in hemoglobin, platelets, WBC, creatinine, need for renal
replacement.
8. Occurrence of serious ventricular arrhythmia
9. Total red blood cell units transfused
10.Major or Clinically Significant Non-Major Bleeding
11. Change from baseline of inflammation and coagulation markers
1. Baseline - Day 29
2. Day 29
3. Baseline-Day 29
4. Baseline-Day 29
5. Within Day 29
6. Till Day 29
7. Baseline- Day 29
8. censored at hospital discharge
9. Baseline -Day 29
10.Baseline -Day 29
11.Baseline- Day 29
Target Sample Size
Total Sample Size="324" Sample Size from India="324" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a randomized, double-blinded, placebo-controlled parallel-design, multicenter, adaptive Phase II/Phase III study to evaluate the safety and efficacy of Ramatroban 75 mg tablet against Placebo in hospitalized subjects with SARS-COV-2 infection along with the standard of care.
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 II
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 III
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 II &III)]
1. To examine lipid mediators, specifically thromboxane A2, PGD2, 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.