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1 Clinical Trial Details (PDF Generation Date :- Wed, 03 Apr :36:28 GMT) CTRI Number CTRI/2010/091/ [Registered on: 20/07/2010] - Last Modified On 18/06/2015 Post Graduate Thesis Type of Trial Type of Study Study Design Public Title of Study Scientific Title of Study No Interventional Drug Randomized, Parallel Group, Placebo Controlled Trial A Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Interferon Alfa-n3 Therapy in Addition to Standard of Care in Adults Hospitalized Due to Acute Severe Influenza A Double Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Interferon Alfa-N3 Therapy in Addition to Standard of Care in Adults Hospitalized Due to Acute Severe Influenza Secondary IDs if Any Secondary ID Identifier Details of Principal Investigator or overall Trial Coordinator (multi-center study) ALFN 101 Designation Affiliation Address Protocol Number Details of Principal Investigator Details Contact Person (Scientific Query) Details Contact Person (Public Query) Phone Fax Designation Affiliation Address Details Contact Person (Scientific Query) Dr Sumbul Siddiqui Medical Monitor Phone Fax Designation Affiliation Address Max Neeman International Max House, 1st Floor, 1, Dr. Jha Marg, Okhla Phase-III, New Delhi New Delhi DELHI ssiddiqui@neemanasia.com Details Contact Person (Public Query) Dr Aditi Parekh Dy. Director Operations Max Neeman International Ready Money Terrace 1st Floor, 167, Dr. A B Road, Worli Naka, Mumbai Mumbai page 1 / 8

2 Source of Monetary or Material Support Primary Sponsor Details of Secondary Sponsor Countries of Recruitment Sites of Study Phone Fax Source of Monetary or Material Support > Hemispherx Biopharma Inc 1617 JFK Boulevard One Penn Center Philadelphia, PA Primary Sponsor Details Hemispherx Biopharma Inc Address 1617 JFK Boulevard One Penn Center Philadelphia, PA Type of Sponsor Max Neeman Medical International Limited List of Countries of Principal Investigator Dr Atul Kakar Dr Amar Pazare Dr Nivedita Moulick DrChellappa Vijaya Ganesh Davaman DrArti Dharaskar Pharmaceutical industry-global Address Max House, 1st Floor 1, Dr. Jha Marg, Okhla Phase-III, New Delhi of Site Site Address Phone/Fax/ Department of Internal medicine, Sir Ganga Ram Hospital Department of Medicine, Seth G. S. Medical College & King Edward Memorial Hospital Department of Medicine, Lokmanya Tilak Municipal Medical College and General Hospital Dr.Kamakshi Memorial Hospital Indrayani Speciality Hospital Department of Internal Medicine, Sir Ganga Ram Hospital, Old Rajender Nagar, New Delhi , New Delhi DELHI Department of Medicine, Seth G.S. Medical College and King Edward Memorial Hospital, Acharya Donde Marg, Parel, Pin Code , Mumbai Department of Medicine, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Pin Code , Mumbai Dr.Kamakshi Memorial Hospital, 1 Radial Road, Pallikaranal, Pin Code , Tamil Nadu Chennai TAMIL NADU Indrayani Speciality Hospital, 156, Neelgiri, Ramdas Peth, Pin Code Nagpur atulkakar@hotmail.com arpazare@hotmail.com ndmoulick@rediffmail.c om c.vijayaganesh@gmail. com indryanihop@yahoo.co m Dr Sandeep Kumar M.V. Hospital and M.V. Hospital and page 2 / 8

3 Details of Ethics Committee Gupta Research Centre Research Centre, 314/30, Mirza Mandi, Chowk, Lucknow , Uttar Pradesh, Lucknow UTTAR PRADESH Dr Vinay Bhomia DrShantanu Sengupta DrNirmal Parmar Sanjivani Super Speciality Hospital Sengupta Hospital & Research Institute Seth Pukhraj Raichand General Hospital Sanjivani Super Speciality Hospital, 1, Uday park society, Nr. Vastrapur Lake, Pin Code , Gujarat, Ahmadabad GUJARAT Sengupta Hospital & Research Institute, Ravinagar Square, Pin Code , Maharashtra, Nagpur Seth Pukhraj Raichand General Hospital, Ramnagar, Sabarmati, Pin Code , Ahmadabad GUJARAT DrDeepak Chauhan Shri Nidan Hospital Shri Nidan Hospital, 27-Vidhut Nagar-A, Pin Code Jaipur RAJASTHAN sandeepkumar.gupta@ rediffmail.com vgb.sanjivani@gmail.co m senguptasp@gmail.co m dr_nirmal82@yahoo.co m drdchauhan22@gmail.c om of Committee Approval Status Date of Approval Is Independent Ethics Committee? Central Medical Research Ethics Committee, Dr. S. M. Patil Hospital, 2nd Floor, Yugdharma Complex, Ramdaspeth, Nagpur , Maharashtra Ethicilin Independent Ethics Committee, Upper 14,Ratnadeep Tower, Opp. C.P. Nagar, Ghatiodiya, Ahmedabad , Gujarat, Ethics Committee for Research in Human Subjects, Seth G S Medical College & KEM Hospital Parel, Mumbai Institutional Ethics Committee Lokmanya Approved 30/05/2011 Yes Approved 21/08/2011 Yes Approved 05/12/2011 No Approved 25/06/2011 No page 3 / 8

4 Regulatory Clearance Status from DCGI Health Condition / Problems Studied Intervention / Comparator Agent Tilak Municipal Medical College & Lokmanya Tilak Municipal General Hospital,Sion, Mumbai Institutional Ethics Committee, M. V. Hospital & Research Centre, 314/30 Mirza Mandi Chowk Lucknow UP Institutional Ethics Committee, Sir Ganga Ram Hospital, Sir Ganga Ram Hospital Marg, Rajinder Nagar, New Delhi Medical Ethics Committee, Dr. Kamakshi Memorial Hospital,Pvt. Ltd, 1 Radial Road, Pallikarnani, Chennai , Tamil Nadu Nagpur Independent Ethics Committee, Nagpur, 303, NIT Lay Out, Trimurti Nagar, Nagpur Maharashtra Sanjivani Hospital Ethics Committee, Sanjivani Super Speciality Hospital, 1-Uday Park Society, Near Vastrapur Lake, Ahmedabad, Gujarat Swastic Independent Ethics Committee, B-130,Modi Nagar,Ajmer Road, Jaipur , Rajasthan Status Approved 09/10/2011 No Approved 13/09/2011 No Approved 15/04/2011 No Approved 02/12/2011 Yes Approved 17/09/2011 No Approved 17/11/2011 Yes Date Approved/Obtained 13/07/2010 Health Type Patients Condition Adult patients hospitalized due to acute severe influenza Type Details Intervention Alferon N Injection 1. Interferon alfa-n3 is a consistent mixture of at least 7 species of alpha interferon (?2,?4,?7,?8,?10,?16, and?17) that arises from the proprietary manufacturing processes. The page 4 / 8

5 Inclusion Criteria active ingredient is a stabilized, preserved interferon alfa-n3 in a buffer solution. 2. The concentrations of interferon alfa-n3 in the study drug is 5.0 million IU/mL. It will be administered as a dose of 0.6 ml subcutaneously for 9-10 days. Comparator Agent Placebo The placebo is identical to the active study medication with the exception that the placebo does not contain interferon alfa-n3. It will be administered subcutaneously 0.6ml for 9-10 days Age From Age To Gender Details Year(s) Year(s) Both Inclusion Criteria 1. Age greater than equal to 18 to less than 60 years of age, male or female. 2. Able to provide informed consent, or for whom consent may be provided by Legally Acceptable Representative or guardian. 3. Subject must have at least two of the following five clinical presentations: a. Oral temperature greater than 38.0 degree Celsius (greater than degree fahrenneit ) b. Oxygen saturation less than 92 percent without supplemental oxygen c.respiration rate less than 24 per minute d. Heart rate greater than 100 per minute e. Systolic Blood pressure less than 100 mm Hg 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 (a feeling that you have a fever), or fatigue) of any severity (mild, moderate, or severe). 6. Onset of illness no more than 72 hours before hospital admission. Note-Time of onset of illness is defined as either (1) the time when the temperature was first measured as elevated (greater than 38.0 degree Celsius (greater than degree fehrenite), 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. Hospitalization criteria- 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 factorsa.presence of chronic obstructive pulmonary disease (COPD) or other chronic lung disease requiring daily pharmacotherapy. b.current history of congestive heart failure or angina. c.presence of diabetes mellitus, clinically stable or unstable. d. Transcutaneous oxygen saturation less than 94 percent 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 greater than 2000 ft above sea level will utilize different criteria for oxygen saturation). e.history of chronic renal impairment not requiring dialysis. page 5 / 8

6 f.serum creatinine greater than 2.0 mg per dl. 8. Diagnosis of clinical influenza with a positive Rapid Antigen Test (RAT) for influenza A and/or influenza B (using a Sponsor-approved test kit, or kits). If available at a site, a sponsor approved ELISA assay for influenza virus may be utilized. 9. Females must be using an effective contraception method or other form of birth control prior to and during the study and use will continue through 4 weeks after completion of study drug administration. 10. Males will ensure that their female partners of childbearing potential will utilize an effective contraceptive method or other form of birth control to avoid pregnancy. Exclusion Criteria Method of Generating Random Sequence Method of Concealment Details Stratified randomization Other Exclusion Criteria 1. Subjects who have developed clinical manifestations of influenza after having been hospitalized for a condition other than confirmed or suspected influenza. 2. Blood platelet count of less than 100 x 109/L. 3. Serum bilirubin greater than 3 mg/dl at time of screening evaluation. 4. Serum ALT or AST greater than 3 times the upper limit of normal at time of screening evaluation. 5. Congestive heart failure of NYHA Class III or Class IV functional status (see Appendix 18.0). 6. Requirement for vasopressor support to maintain satisfactory hemodynamic status at time of screening evaluation. 7. Serum creatinine greater than 3.0 mg/dl at time of screening evaluation. 8. Subjects who require peritoneal dialysis or hemofiltration. 9. Altered neurologic status as defined by a Glasgow Coma Score of less than or equal to 11, unless medically induced (see Appendix 19.0). 10. Females who are pregnant (positive urine or serum pregnancy test at screening evaluation) or lactating. 11. Actively undergoing systemic chemotherapy or radiotherapy treatment for a malignancy. 12. A history of allergy to eggs or mice. 13. An initial peripheral absolute neutrophil count below 1500/mm3 14. Prior hematopoietic stem cell transplantation or solid organ transplant during the previous 4 months. 15. Presence of a pre-existing chronic infection that is undergoing or requiring medical therapy (i.e., tuberculosis). 16. 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. 17. Previous treatment with Interferons (alpha, beta or gamma) of any origin (recombinant or human leukocyte-derived). 18. 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. 19. Subjects who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol. 20. Subjects who can not receive subcutaneous injections. 21. Subjects with a history of HIV disease. page 6 / 8

7 Blinding/Masking Participant and Investigator Blinded Primary Outcome Outcome Timepoints To determine if Alferon N Injection treatment reduces the Time to Clinical Stability (days) defined as the normalization of the following five vital signs: temperature 38 C oral; oxygen saturation 92%; respiratory rate 24/minutes; heart rate 100/minute; and systolic BP 100 mmhg 10 hours (+ 2 hours) after the last dose of interferon prior to hospital discharge and at the follow up visit on day 30+3 Secondary Outcome Outcome Timepoints 1. Safety of Alferon N Injection at the dosage used in this study. 2. Time to hospital discharge ability (days) defined as the duration of time from admission to the hospital to when the attending physician declares that subject is ready to be discharged as a result of improvement or resolution of the 5 elements that clinical stability. 3. Time to hospital discharge (days) 10 hours(+ 2 hors after the last dose of interferon prior to hospital discharge and at the follow up visit on day 30+3 Target Sample Size Phase of Trial Phase 2 Date of First Enrollment () Date of First Enrollment (Global) Estimated Duration of Trial Recruitment Status of Trial (Global) Recruitment Status of Trial () Publication Details Brief Summary Total Sample Size=60 Sample Size from =60 21/08/2010 No Date Specified Years=3 Months=0 Days=0 Not Applicable Not Applicable This is a prospective, adaptive group sequential, multicenter, and double blind, placebo-controlled study of the efficacy and safety of Alferon N Injection in hospitalized patients due to acute severe influenza. After screening and enrollment, subjects will receive standard institutional symptomatic supportive care and antivirals. Patients randomized to Alferon N Injection 3 MU will receive 3 million units of IFN alfa-n3 (0.6 ml) as an initial subcutaneous (SQ) dose immediately upon entry into the study and within eight (8) hours of hospital admission. This will be followed by a SQ dose of IFN alfa-n3 (0.6 ml) 12 hours later, and then 0.6 ml by SQ injection every 24 hours to complete a maximum of 10 doses over 9 or 10 days depending on the timing of the first two doses. NOTE: Dose 3 is to be given 24 hours after Dose 2. Subjects randomized to placebo will receive an equivalent volume of placebo in place of the active study drug (Alferon N Injection ). Patients will receive study drug (active or placebo) up to a maximum of 10 doses until hospital discharge, which may occur earlier than day 10 (i.e. day 5). Patients randomized to the Placebo group will receive the same schedule of SQ doses but patients will receive only the page 7 / 8

8 Powered by TCPDF ( vehicle of Alferon N Injection. Subjects will return to the hospital at day 30+3 after the first injection of study drug for a follow up evaluation. If a patient remains hospitalized for more than 26 days, then Day 27 will be considered as Day The difference in the event time distribution functions for time to clinical stability will be compared between the 2 treatment groups using a Cox proportional hazards regression model. After 60 patients have either completed the evaluation phase of the study or withdrawn prematurely, a single pre-specified interim assessment will be performed using the intra-patient time to clinical stability. The re-estimation of the final target sample size may be increased to ensure adequate statistical power if the conditional power after 60 patients is?50%. page 8 / 8