Clinical trial of otilimab in patients with severe pulmonary COVID-19 related disease.
Scientific Title of Study
A randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety of otilimab IV in patients with severe pulmonary COVID-19 related disease.
Trial Acronym
OSCAR study
Secondary IDs if Any
Secondary ID
Identifier
2020-001759-42
EudraCT
NCT04376684
ClinicalTrials.gov
Protocol No. 214094 version 2 dated 02Jul2020
DCGI
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Rashmi Chitgupi
Designation
Director Clinical Management
Affiliation
PPD Pharmaceuticals Development India Private Limited
Address
PPD Pharmaceuticals Development India Private Limited
101, A Wing, Fulcrum, Hiranandani Business Park
Sahar Road, Andheri East,
Mumbai MAHARASHTRA 400099 India
Phone
91-02266022900
Fax
91-02266022999
Email
rashmi.chitgupi@ppdi.com
Details of Contact Person Public Query
Name
Rashmi Chitgupi
Designation
Director Clinical Management
Affiliation
PPD Pharmaceuticals Development India Private Limited
Address
PPD Pharmaceuticals Development India Private Limited
101, A Wing, Fulcrum, Hiranandani Business Park
Sahar Road, Andheri East,
Mumbai MAHARASHTRA 400099 India
Phone
91-02266022900
Fax
91-02266022999
Email
rashmi.chitgupi@ppdi.com
Source of Monetary or Material Support
GlaxoSmithKline Research & Development Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Primary Sponsor
Name
GlaxoSmithKline Research and Development Limited
Address
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
PPD Pharmaceutical Development India Private Limited
PPD Pharmaceutical Development India Private Limited. 101, A Wing, Fulcrum, Hiranandani Business Park
Sahar Road, Andheri East, Mumbai 400099
India
Countries of Recruitment
Argentina Belgium Brazil Canada Chile Colombia France India Japan Mexico Netherlands Peru Poland South Africa Spain United Kingdom United States of America Russian Federation
Government Medical College and Hospital-Aurangabad
Department of Medicine, Government Medical College and Hospital, Panchakki Road
Aurangabad 431001, Maharashtra, India
Aurangabad MAHARASHTRA
919922931527
mabhattacharya@gmail.com
Dr Dipti Chand
Government Medical College and Hospital-Nagpur
Department of Medicine, ward no 44, Government Medical College and Hospital, Medical College Square Road,
Nagpur 440003, Maharashtra, India
Nagpur MAHARASHTRA
919823257601
Dachand.ngp@gmail.com
Dr Kapil Zirpe
Grant Medical Foundation, Ruby Hall Clinic
Neuro Trauma Unit, Sanghavi Building, Second floor, Grant Medical Foundation, Ruby Hall Clinic, 40, Sassoon Road,
Pune 411001, Maharashtra, India Mumbai MAHARASHTRA
919822844212
kapilzirpe@gmail.com
Dr Ajay Bharat Jhaveri
Kasturba Hospital for Infectious diseases
Department of Medicine, Kasturba Hospital for Infectious diseases,
Sane guruji Marg, Mumbai 400011 Maharashtra, India
Mumbai MAHARASHTRA
919867433330
drajayjhaveri@gmail.com
Dr Umar Quadri Syed
Mahatma Gandhi Mission (MGM) Medical College & Hospital
Department of General Medicine, Mahatma Gandhi Missions (MGM) Medical College & Hospital, N 6, CIDCO,
Aurangabad 431003, Maharashtra, India.
Aurangabad MAHARASHTRA
919923798702
umarazmed@gmail.com
Dr Ritesh Aggarwal
Max Smart Super Speciality Hospital
Department of Critical Care- Intensive Care, Max Smart Super Speciality Hospital, Saket (A Unit of Gujarmal Modi Hospitals & Research Centre for Medical Sciences), Mandir Marg, Press Enclave Road, Saket, New Delhi 110017, India New Delhi DELHI
919650923723
Ritesh.Aggarwal@maxhealthcare.com
Dr Tanmay Banerjee
Medica Super Specialty Hospital
Department of Internal medicine, Medica Super Specialty Hospital, 127, Mukundapur, E,M.Bypass,
Kolkata 700099, West Bengal, India
Kolkata WEST BENGAL
919433427574
tanmay.banerjee@medicasynergie.in
Dr Reema Kashiva
Noble Hospital Pvt Ltd
Room no. 08,Ground floor, Department of Medicine, Noble Hospital Pvt Ltd, 153, Magarpatta City Road, Hadaspar, Pune 411013, Maharashtra, India Pune MAHARASHTRA
919923798702
reemakashiva@gmail.com
Dr Rimita Dey
Peerless Hospitex Hospital and Research Center Limited
Intensive Care Unit, Second floor, Peerless Hospitex Hospital and Research Center Limited, 360, Panchsayar, Kolkata 700094, West Bengal, India Kolkata WEST BENGAL
919836896638
rimitadey@yahoo.co.in
Dr Chhuttan Lal Nawal
S.M.S. Medical College and Attached Hospitals
Ground Floor G-1, Department of Medicine, Dhanvantri, OPD Block, S.M.S. Medical College and Hospitals, Ground Gloor, G-1, Department of Medicine, Dhanvantri OPD Block, Jaipur 302004, Rajasthan, India Jaipur RAJASTHAN
919414044005
drclnawal@gmail.com
Dr Keyur Brahme
Sir Sayajirao General Hospital (SSG Hospital)
Department of General Medicine, Sir Sayajirao General Hospital (SSG Hospital), Medical College Baroda,
Maharaja Sayajirao University of Baroda, Jail Road (Indira Avenue), Anandpura, Vadodara
390001, Gujarat, India
Vadodara GUJARAT
Fully human anti-GM-CSF monoclonal antibody (mAb),
frequency : Once only on day 1,
Route of administration : IV infusion,
Duration of therapy : therapy will be administered approximately over 1 hour
Comparator Agent
Placebo in addition with Standard of care
Sterile 0.9% (w/v) sodium chloride solution,
Frequency: Once only on day 1,
Route of administration : IV infusion,
Duration of therapy : therapy will be administered approximately over 1 hour
Inclusion Criteria
Age From
18.00 Year(s)
Age To
79.00 Year(s)
Gender
Both
Details
1. Age ≥18 years and ≤79 years at the time of obtaining informed consent.
2. Participants must:
a. have positive SARS-CoV-2 result (any validated test, e.g. RT-PCR [performed on an appropriate specimen; e.g. respiratory tract sample])
b. AND be hospitalized due to diagnosis of pneumonia (chest X-ray or computerized tomography [CT] scan consistent with COVID-19)
c. AND be developing new onset of oxygenation impairment defined as SpO2 ≤90% on room air
d. AND requiring any of the following:
1. high-flow oxygen (≥15L/min)
2. non-invasive ventilation (e.g. CPAP, BiPAP)
3. mechanical ventilation ≤48h prior to dose
e. AND have increased biological markers of systemic inflammation (either CRP>ULN or serum ferritin >ULN).
3. No gender restriction.
4. Female participants must meet and agree to abide by the contraceptive criteria detailed in Appendix 4. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
o Is a woman of non-childbearing potential (WONCBP) as defined in Section 9.4: Contraceptive and Barrier Guidance.
OR
o Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Section 9.4 during the study intervention period and for at least 60 days after the last dose of study intervention (sexual abstinence is acceptable if it is the participant’s normal practice).
o If not consistently on a highly effective method of contraception (Section 9.4) during hospitalization, the participant must agree to a highly effective contraception plan if discharged before Day 60.
o The investigator should evaluate potential for contraceptive method failure (e.g. Noncompliance, recently initiated) in relation to the first dose of study intervention.
o A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) at hospital admission or before the first dose of study intervention. See Section 7.3.5 Pregnancy Testing (additional requirements for pregnancy testing during and after study intervention).
o The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
5. Capable of giving written informed consent as described in Section 9.1.3. If participants are not capable of giving written informed consent, alternative consent
procedures will be followed as detailed in Section 9.1.3.
ExclusionCriteria
Details
1. Progression to death is imminent and inevitable within the next 48 hours, irrespective of the provision of treatments, in the opinion of the investigator.
2. Multiple organ failure according to the investigator’s judgement or a Sequential Organ Failure assessment (SOFA score) >10 if in the ICU.
3. Extracorporeal membrane oxygenation (ECMO) hemofiltration/dialysis, or high dose (>0.15mcg/kg/min) noradrenaline (or equivalent) or more than one vasopressor.
4. Current serious or uncontrolled medical condition (e.g. significant pulmonary disease such as severe COPD or pulmonary fibrosis, heart failure [NYHA class III or higher], significant renal dysfunction, acute myocardial infarction or acute cerebrovascular accident within the last 3 months) or abnormality of clinical laboratory tests that, in the investigators judgment, precludes the participants safe participation in and completion of the study.
5. Untreated systemic bacterial, fungal, viral, or other infection (other than SARSCoV-2).
6. Known active tuberculosis (TB), history of untreated or incompletely treated active or latent TB, suspected or known extrapulmonary TB.
7. Known HIV regardless of immunological status.
8. Known HBsAg and/or anti-HCV positive.
9. Currently receiving radiotherapy, chemotherapy or immunotherapy for malignancy.
10. Received monoclonal antibody therapy (e.g. tocilizumab, sarilumab) within the past 3 months prior to randomization, including intravenous immunoglobulin, or planned to be received during the study.
11. Received immunosuppressant therapy including but not limited to cyclosporin, azathioprine, tacrolimus, mycophenolate, JAK inhibitors (e.g. baricitinib, tofacitinib, upadacitinib) within the last 3 months prior to randomization or planned to be received during the study.
Note: Participants with an organ transplant are therefore excluded (except patients with corneal transplants not requiring immunosuppression).
12. History of allergic reaction, including anaphylaxis to any previous treatment with an anti-GM-CSF therapy.
13. Received COVID-19 convalescent plasma within 48 hours of randomization.
Note: Participants who have received COVID-19 convalescent plasma but continue to worsen in the 48 hours after infusion of the convalescent plasma, in the opinion of the investigator, will become eligible for the study.
14. Currently receiving chronic oral corticosteroids for a non-COVID-19 related condition in a dose higher than prednisone 10 mg or equivalent per day.
15. Treatment with an investigational drug within 30 days of randomization.
16. Participating in other drug clinical trials, including for COVID-19.
17. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x upper limit of normal (ULN).
18. Platelets <50,000/mm3.
19. Haemoglobin ≤9 g/dL.
20. Absolute neutrophil count (ANC) <1.5 x 10 raised to 9/L (neutropenia ≥ Grade 2).
21. Estimated GFR ≤30 mL/min/1.73meter square.
22. Pregnant or breastfeeding females.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To compare the efficacy of otilimab IV versus placebo
Participants alive and free of respiratory failure at Day 28
Secondary Outcome
Outcome
TimePoints
To compare the efficacy of otilimab IV versus placebo
To compare the safety and tolerability of otilimab IV versus placebo
All-cause mortality and Time to all-cause mortality up to Day 60
Participants alive and free of respiratory failure at Day 7, 14, 42, and 60
Time to recovery from respiratory failure up to Day 28
Participants alive and independent of supplementary oxygen at Day 7, 14, 28, 42, and 60
Time to last dependence on supplementary oxygen to Day 28
Admission to ICU and Time to final ICU discharge,final hospital discharge up to Day 28
Occurrence of adverse events (AEs) & (SAEs) [up to Day 60]
Target Sample Size
Total Sample Size="800" Sample Size from India="72" 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)?
Brief Summary
This is a randomized, double-blind, placebo-controlled, study evaluating the efficacy and safety of otilimab IV in patients with severe pulmonary COVID-19 related disease. The aim of this study is to evaluate the benefit-risk of a single infusion of otilimab in addition to standard treatment of care in treatment of patients with severe pulmonary COVID-19 related disease.