A clinical trial to evaluate the safety and efficacy of peramivir administered intravenously in addition to standard of care compared to standard of care alone in adults and adolescents who are hospitalized due to serious influenza
Scientific Title of Study
A Phase 3, multicenter, randomized double-blind, controlled study to evaluate the efficacy and safety of peramivir administered intravenously in addition to standard of care compared to standard of care alone in adults and adolescents who are hospitalized due to serious influenza.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
BCX1812-301
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Nevin Kishore
Designation
Senior Consultant- Internal Medicine
Affiliation
Max Super Speciality Hospital
Address
Max Super Speciality Hospital,1-Press Enclave Road,Saket, New Delhi-110017
South DELHI 110017 India
Phone
91-9818138111
Fax
91-11-26565060
Email
nevin.kishore@maxhealthcare.com
Details of Contact Person Scientific Query
Name
Dr Purabi R Sharma
Designation
Medical Monitor
Affiliation
Address
Max Neeman International
Address Line 2: Max House, 1, Dr. Jha Marg, Okhla Phase-III
City: New Delhi
State: New Delhi
Postal Code: 110020
Country: India
South DELHI 110020 India
Phone
91-9560786675
Fax
91-11-41001945
Email
psharma@neemanasia.com
Details of Contact Person Public Query
Name
Dr Shariq Anwar
Designation
Director Operations
Affiliation
Address
Address Line 1: Max Neeman International
Address Line 2: Max House, 1, Dr. Jha Marg, Okhla Phase-III
City: New Delhi
State: New Delhi
Postal Code: 110020
Country: India
BioCryst Pharmaceuticals, 4505 Emperor Blvd, Suite 200, Durham, North Carolina, 27703, United States of America, Phone Number: 919 226 5857
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Dr Shariq Anwar
Max Neeman International
Max House,1st Floor
1 Dr. Jha Marg, Okhla III
New Delhi- 110020
Countries of Recruitment
Argentina Belgium Brazil Bulgaria Canada Chile Czech Republic Germany Hungary India Israel Latvia Lebanon Peru Poland Russian Federation Serbia Slovakia South Africa Ukraine United Kingdom United States of America
Department-Internal Medicine,No. 154, P.H.Road, Kilpauk, Chennai TAMIL NADU
9962481030 7940011622 drtvd@rediffmail.com
Dr Dhiman Sen
Apollo Gleneagles Hospitals
Apollo Gleneagles Hospitals, Kolkata, Department of Clinical Trial & Research, 58 Canal Circular Road, West Bengal, Kolkata-700054, India
Kolkata WEST BENGAL
Department-Medicine and Pulmonology,# 258/A Bommasandra Industrial Area, Anekal Bangalore KARNATAKA
9844097170 80-27835208 bvmuralimohan@gmail.com
Dr Dipak Dantara
Nidhi Hospital
Department-Internal Medicine,Shree Kunj, Clinical Research Unit, 4th
floor, Stadium Commerce College Road
Ahmadabad GUJARAT
9825011855 40232198 d_dantara@hotmail.com
Dr Rajendra S Rabade
Niramaya Hospital Pvt. Ltd.
Niramaya Hospital Pvt. Ltd.,
Survey No.-4742, Behind Jaihind Petrol Pump, Next to Chinchwad (East) Post Office, Chinchwad, Pune- 411019, Maharashtra, India Pune MAHARASHTRA
Ethics Committee, Niramaya Hospital Pvt. Ltd.,Survey No.-4742, Behind Jaihind Petrol Pump, Next to Chinchwad (East) Post Office, Chinchwad, Pune- 411019, Maharashtra, India
Approved
Ethics Committee,S.P.Medical College & AG of Hospitals, PBM Hospital & AG of Hospital, Bikaner-334003, Rajasthan, India
Approved
Ethics Committee,Sir Ganga Ram Hospital,Old Rajinder Nagar Road,New Delhi, 110060, India
Approved
Ethics CommitteeKrishna Institute of Medical Sciences Ltd
Approved
Fortis Escorts, Hospital & Research Center Ltd,Neelam Bata Road,Faridabad-121001,Haryana,India , Independent Ethics Committee,Fortis Escorts, Hospital & Research Center Ltd,Neelam Bata Road,Faridabad-121001,Haryana,India
Approved
Global Health Concern Ethics Committee, Maratha Samaj Building, Sakkardara Chowk, Nagpur-440009
Approved
Global Hospitals and Health City, 439,Cheran Nagar,Perumbakkam,Chennai-600100,India ,Institutional ethics Committee,Global Hospitals and Health City, Institutional ethics Committee,Global Hospitals and Health City, 439,Cheran Nagar,Perumbakkam,Chennai-600100,India
Approved
Hirabai Cowasji Jehangir Medical Research Institute And Jehangir Clinical Development Centre Ethics Committee, 32, Sasoon Road,Pune-411001,Maharashtra,India
Approved
Human Research Ethics Committee, H M Patel Centre for Medical Care and Education, Karamasad-388325,Gujarat,India
Approved
Independent Ethics Committee,Fortis Escorts Heart Institute & Research Center,Okhla Road,New Delhi-110025,India
Approved
Independent Ethics Committee,Fortis Escorts, Hospital & Research Center Ltd,Neelam Bata Road,Faridabad-121001,Haryana,India
Approved
Institutional Ethics Commitee Baroda Medical College & SSG Hospital, Jial Road (India Avenue),Vadodara-390001,India
Approved
Institutional Ethics Commitee Sher-i-Kashmir Institute of Medical Sciences
Approved
Institutional Ethics Committee Lakshmi Hospital, A M Road, Perumbavoor, Ernakulum, 683542, Kerala, India
Noble Hospital Institutional Ethics Committee, Noble Hospital Pvt Ltd, 153, Magarpatta City Road, Hadapsar, Pune- 411013 Maharashtra, India
Approved
Poona Medical Research Foundation, Ruby Hall Clinic, 40,Sassoon Road, Pune-411001,Maharashtra,India
Approved
Research Independent Ethics Committee, Surat
Approved
Sahyadri Hospitals Ltd Ethics Committee, 30 C Erandwane Karve Road,Pune-411004
Approved
Sapthagiri Institute of Medical Sciences and Research Center Institutional EC No.15, Chikkasandra, Hesaraghatta Main Road, Bangalore-560090, Karnataka, India
Approved
Shatabdi Hospital Ethics Committee,Opp. To Mahamarg Bus Stand, Mumbai Naka,Nashik-422005,Maharashtra,India
2. Able to provide informed consent, or for whom consent may be provided by guardian, unless informed consent provided by a guardian or a legally authorized representative is not consistent with applicable local or ethical concerns, procedures, directives and/or guidelines.
3. Subject must have at least one of the following clinical presentations at Screening:
a. Oral temperature ≥ 38.0 degree C (≥100.4 F), ≥38.6 degree C (≥101.4 F) tympanic or rectal OR
b. Oxygen saturation 92%, OR
4. Presence of at least one respiratory symptom (cough, sore throat, or nasal congestion) of any severity (mild, moderate, or severe).
5. Presence of at least one constitutional symptom (headache, myalgia, feverishness, or fatigue) of any severity (mild, moderate, or severe).
6. Onset of illness no more than 72 hours before presentation. Note: Time of onset of illness is defined as the earlier of either (1) the time when the temperature was first measured as elevated, OR (2) the time when the subject experienced the presence of at least one respiratory symptom AND the presence of at least one constitutional symptom.
7. Either:
Severity of illness that, in the Investigators judgment, justifies hospitalization of the subject for supportive care.
OR
Presence of one or more of the following factors:
a. Age ≥60 years.
b. Presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy.
c. Current history of congestive heart failure or angina.
d. Presence of diabetes mellitus, clinically stable or unstable.
e. Transcutaneous oxygen saturation 94% without supplemental oxygen for at least 5 minutes, or a medically significant decrease in oxygen saturation from an established baseline value (an investigative site at altitude 2000 ft above sea level will utilize different criteria for oxygen saturation).
f. History of chronic renal impairment not requiring peritoneal dialysis.
g. Serum creatinine 2.0 mg/dL or 200 μmol/L.
8. Diagnosis of Influenza by satisfying one of the following:
a. Clinical Influenza with Positive Diagnostic Test. Subjects who have a positive rapid antigen test (RAT) for influenza A and/or influenza B (using a Sponsor-approved test kit), or positive test (using other methodology) for influenza A and/or B virus antigen or RNA performed in a clinical laboratory at the screening/enrollment evaluation are eligible for enrollment.
b. Clinical Influenza with Negative Rapid Antigen Test (RAT). Subjects with a negative RAT test may be enrolled once the site has been approved by the Sponsor to enroll such subjects, based on documentation of an outbreak of influenza in the community. An influenza outbreak may be documented in the catchment area of the hospital via one of the following methods: 1) local confirmation of influenza A or B infection in the current influenza season by a) the institutions local laboratory, or b) the local public health system, or c) the national public health system, or d) a laboratory of a recognized multinational influenza surveillance scheme such as the European Influenza Surveillance Network (EISN); 2) prior enrollment of a RAT positive subject into this study at the same institution in the current influenza season.
ExclusionCriteria
Details
1. Subjects who have been hospitalized for greater than 24 hours (not including time spent in the Emergency Department).
2. Treatment with any dose(s) of rimantadine, amantadine, ribavirin, zanamivir, or oseltamivir in the previous 7 days.
3. Blood platelet count of 20 x 109/L at the time of the screening evaluation.
4. Serum bilirubin 6 mg/dL or 102.6 μmol/L at time of screening evaluation.
5. Serum ALT or AST 5 times the upper limit of normal at time of screening evaluation.
6. Congestive heart failure of NYHA Class III or Class IV functional status.
7. Serum creatinine 5.0 mg/dL or 442 μmol/L at time of screening evaluation.
8. Subjects who require peritoneal dialysis.
9. Altered neurologic status as defined by a Glasgow Coma Score of ≤ 9, unless medically induced.
10. Females who are pregnant (positive urine or serum pregnancy test at screening evaluation) or breastfeeding.
11. Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy. Subjects who have completed treatment 30 days prior to enrollment are not excluded. Hormone treatment for cancer is also not excluded.
12. Prior hematopoietic stem cell transplantation or solid organ transplant during the previous 4 months.
13. HIV infection with a known CD4 count 200 cells/mm3 unless on a stable highly active antiretroviral therapy (HAART) for at least 6 months.
14. Presence of a pre-existing chronic infection that is undergoing or requiring medical therapy (eg, tuberculosis). Subjects with chronic osteomyelitis or Hepatitis B or C not requiring treatment are not excluded.
15. Presence of any pre-existing illness that, in the opinion of the investigator, would place the subject at an unreasonably increased risk through participation in this study.
16. Previous treatment with intravenous or intramuscular peramivir.
17. Participation as a subject in any study of an experimental treatment for any condition within the 30 days prior to the time of the screening evaluation.
18. Subjects diagnosed with Cystic Fibrosis
19. Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol
20. Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
To evaluate the effect of treatment with peramivir plus standard of care (SOC) compared to placebo plus SOC on time to clinical resolution in adults and adolescents who are hospitalized with influenza.
To evaluate the following for peramivir plus SOC v/s placebo plus SOC:
1. safety & tolerability
2. changes in viral shedding associated with the treatment
3. effect on time to alleviation of symptoms, time to resumption of usual daily activities, time to hospital discharge, incidence & duration of ICU admission after initiation of treatment, incidence of influenza-related complications & mortality
4. changes in viral phenotype & genotype between baseline & post-treatment samples
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a multinational, randomized, double-blind, controlled study comparing the efficacy and safety of peramivir (600 mg) versus placebo administered intravenously once daily for 5 days in addition to the institutions standard of care in adults and adolescents 12 years of age and older who are hospitalized due to influenza. Total number of subjects to be enrolledglobally is 306out of which 100 subjects to be enrolled from India
Subjects with signs and symptoms compatible with influenza infection will be evaluated for participation. Eligible subjects will be unequally randomized 2(Peramivir):1(Placebo) to receive one of the two treatments. The primary objective of the trial is to evaluate the effect of treatment with peramivir plus standard of care (SOC) compared to placebo plus SOC on time to clinical resolution in adults and adolescents who are hospitalized with influenza.