CTRI/2019/01/016851 [Registered on: 02/01/2019] Trial Registered Prospectively
Last Modified On:
18/07/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A clinical trial to compare the effect of Single Transition from Enbrel® Auto-Injector (AI) to YLB113 Auto-Injector in Patients with Active Rheumatoid Arthritis (RA).
Scientific Title of Study
Randomized, Controlled Open Label Clinical Study to Compare the Impact of Single Transition from Enbrel® Auto-Injector (AI) to YLB113 AI on Safety, PK and Compare Usability of Both AIs in Patients with Active Rheumatoid Arthritis (RA).
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
LRP/YLB113/2017/001
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Chirag Shah
Designation
Associate Director
Affiliation
Lupin Limited
Address
Survey No. 46 A / 47 A, Village Nande, Taluka Mulshi, Pune, Maharashtra, India
Pune MAHARASHTRA 412115 India
Phone
020-66749068
Fax
Email
chiragshah@lupin.com
Details of Contact Person Scientific Query
Name
Dr Dhananjay Bakhle
Designation
Executive Vice President
Affiliation
Lupin Limited
Address
Survey No. 46 A / 47 A, Village Nande, Taluka Mulshi, Pune, Maharashtra, India
Pune MAHARASHTRA 412115 India
Phone
020-66749054
Fax
Email
dhananjaybakhle@lupin.com
Details of Contact Person Public Query
Name
Dr Dhananjay Bakhle
Designation
Executive Vice President
Affiliation
Lupin Limited
Address
Survey No. 46 A / 47 A, Village Nande, Taluka Mulshi, Pune, Maharashtra, India
H No 6-3-248/2 Road No: 1 Banjara Hills Hyderabad- 500034
CARE Hospital, H No 8-2-620/A-E Road No: 10 Banjara Hills Hyderabad- 500034
Hyderabad TELANGANA
9246544284
jkishorek71@yahoo.co.in
Dr Chandrashekara Srikantiah
ChanRe Rheumatology and Immunology Center and Research
No. 414/65, 20th Main, West of Chord Road, 1st Block, Rajajinagara, Bangalore-560010, Karnataka, India Bangalore KARNATAKA
9845071151
chandrashekara_s@yahoo.com
Dr Naisar Dilip Nahar
Chopda Medicare and Research Centre Pvt. Ltd, Magnum Heart Institute
3/5 Patil Lane No.1, Laxminagar, Near KBH Vidyalaya, Canada Corner, Nashik-422005, Maharashtra Nashik MAHARASHTRA
9970222227
dr.naisar@yahoo.com
Dr Ramkrishna Uppuluri Rao
Gleneagles Global Hospital
6-1-1070/1to4, Lakdi ka pool, Hyderabad-500004, Telangana, India Hyderabad TELANGANA
9849160640
urkrao@yahoo.com
DrShajit Sadanand
Government Medical College
Dept General Medicine, Government Medical College, Kozhikode-673009, Kerala, India Kozhikode KERALA
9447338860
shajit_sadanand@yahoo.com
Dr Nachiket Kulkarni
Jehangir Clinical Development Centre Pvt. Ltd
Jehangir hospital Premises,32 Sassoon Road
Pune- 411001,Maharashtra, India
Pune MAHARASHTRA
9923243860
drnachiketkulkarni@gmail.com
Dr Ramaswamy Subramanian
JSS Hospital
Room no: 1020, Department of Rheumatology and Immunology, JSS Hospital, MG Road, Mysore-570004 Mysore KARNATAKA
9945472441
subsan05@gmail.com
Dr Archana Uppin
LES Dr. Prabhakar Kore Hospital and MRC
K Nehru Nagar, Belagavi-590010 Belgaum KARNATAKA
9844175418
drarchanaK85@gmail.com
Dr Nilesh Patil
Lifepoint Multidisciplinary Hospital
145/1, Mumbai Bangalore Highway, Near Hotel Sayaji, Wakad, Pune-411057, Maharashtra India Pune MAHARASHTRA
2066434366
patilnj81@gmail.com
Dr Pradeep Kumar
Mazumdar Shaw Medical Centre
Unit of Narayana Health, #258/A Bommasandra Industrial Area, Anekal Taluk, Hosur Road, Bangalore-560099 Bangalore KARNATAKA
8792993073
pradeepkumar@nhs.net
Dr Girish Bhatia
Medipoint Hospital Pvt. Ltd
241/1, New D.P Road, Near Sai Heritage, Aundh, Pune 411007 Pune MAHARASHTRA
7387003636
drbhatia.pentagon@gmail.com
Dr Reena Sharma
Medlink Hospital Research Centre
Basement Medlink Hospital Research Centre, 132 ft Ring Road, Shyamal Cross Road, Satellite, Ahmedabad-380015 Gujarat, India Ahmadabad GUJARAT
9978662400
reena141@gmail.com
Dr Bankimchandra Nanubhai Desai
Nirmal Hospital Pvt. Ltd
Ring Road, Surat, Gujarat-395002, India Surat GUJARAT
9845085931
drbankim.desai@gmail.com
Dr Rahul Katta
S.R. Kalla Memorial Gastro and General Hospital
78-79 Dhuleshwar Garden, Behind HSBC Bank, Sardar Patel Marg, C-Scheme, Jaipur-302001, Rajasthan, India Jaipur RAJASTHAN
9829010401
rahulkatta@hotmail.com
Dr Avinash Agarwal
Shri Nidaan Hospital and Hope Fertility Centre
27-Vidhu Nagar-A, Ajmer Road, Jaipur 302006, Rajasthan, India Jaipur RAJASTHAN
9829052451
dr.avitanu@gmail.com
DrSandeep Kharkar
Shrikrishna Hrudayalaya and Critical Care Centre
Tikekar Road, Congress Nagar Square, Dhantoli, Nagpur-440012, Maharashtra, India Nagpur MAHARASHTRA
9370808866
drksandeep@gmail.com
Dr Praveen Jadhav
Sujata Birla Hospital and Medical Research Center
Opposite to Bytco College, Nashik Pune Highway, Nashik Road, Nashik-422101, Maharashtra, India Nashik MAHARASHTRA
99822055612
praveenjjadhav@gmail.com
DrVikram Muralidhar Haridas
Sushruta Mutltispeciality Hospital and Research Centre Pvt. Ltd
P.B. Road, Vidyanagar, Hubballi-580021, Karnataka, India Dharwad KARNATAKA
9343649883
haridasvikram@yahoo.co.in
Dr Arindam Nandy Roy
Yashoda Hospital
Behind Hari Hara Kala Bhavan, S. P. Road, Secunderabad- 500003 Hyderabad TELANGANA
9849279830
doctor.arindam@yahoo.com
Dr Rajendra Vara Prasad Irlapati
Yashoda Hospital
Raj Bhavan Road, Somajiguda, Hyderabad-500082, Telangana, India Hyderabad TELANGANA
Supplied as a single-dose‚ Auto-injector containing fixed dose of 50 mg (50 mg/ml) subcutaneous injection of Etanercept per week. The total duration of study is 16 weeks (screening period of 4 weeks and treatment duration is of 12 weeks). The study drug will be administered every week during study period.
Intervention
YLB113
Supplied as Single-dose‚ Auto-Injector containing fixed dose of 50 mg (50 mg/ml) subcutaneous injection of Etanercept per week. The total duration of study is 16 weeks (screening period of 4 weeks and treatment duration is of 12 weeks). The study drug will be administered every week during study period.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1.Patients must be able and willing to give written informed consent prior to any study related procedures
2.Patients diagnosed with RA according to the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.
3.Patients who have moderate to severe disease activity with DAS28 score >3.2 and CDAI score ≥10.1.
4.Patients classified as Global Functional Assessment Class I, II, or III, according to the revised ACR criteria
5.Patients who have been treated with MTX for at least 3 months at an optimum dose (10-25 mg/week, not exceeding the local approved dose) that has remained stable for at least 4 weeks prior to screening, based on patient history.
6.Patients who have completed washout of minimum 7 days for Azathioprine, Sulfasalazine and Cyclosporine, 4 weeks for hydroxychloroquine and Auranofin (oral gold) prior to first dose of IP.
Transition Period:
7.Patients who complete 6 week Lead-in Period.
8.Patients without drug related serious adverse events (SAEs) or unresolved Grade 3 or higher adverse events in Lead-in Period.
ExclusionCriteria
Details
Patients who meet any of the following criteria should be disqualified from entering the study:
1.Patients with known hypersensitivity to Etanercept or any other components of the study drug
2.Patients allergic to latex (the needle cover within the needle cap of the Etanercept AI contains latex, which may cause allergic reactions in individuals sensitive to latex)
3.Patients suffering from acute or chronic, localized or disseminated infections (bacterial/fungal/viral) or sepsis, or patients with a history of recurring infections, or those who are at an increased risk of developing infections or sepsis within 3 months prior to screening
4.Patients with active tuberculosis (TB), prior history of unsuccessfully treated TB, latent TB, or patients who are positive for TB test viz. QuantiFERON®-TB Gold test
5.Patients with a history of septic arthritis of native joints within 12 months prior to screening, or any prior history of septic arthritis of prosthetic joints
6.Patients diagnosed with other rheumatic diseases, autoimmune diseases, connective tissue diseases, or immune deficiencies (viz., psoriasis, psoriatic arthritis, primary Sjogren’s syndrome, systemic lupus erythematosus, or demyelinating diseases such as multiple sclerosis)
7.Patients with active or prior history of malignancies within 5 years prior to screening (except for successfully treated non-metastatic basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix)
8.Patients with a prior history of blood dyscrasias.
9.Patients with a history of alcohol, drug, or chemical abuse in the past 2 years prior to screening
10.Patients who received any live or attenuated vaccines within 4 weeks of screening
11.Patients who received leflunomide within 3 months of screening.
12.Patients previously treated with any other biologic response modifiers for any auto-immune indications (including but not limited to tocilizumab, adalimumab, anakinra, abatacept, infliximab, golimumab, etanercept, certolizumab and tofacitinib) within 6 months and patients treated with rituximab within 12 months prior to randomization.
13.Patients with serious systemic infections (e.g., patients who test positive for hepatitis B surface antigen [HBsAg], hepatitis B core antibody [HBcAb] & hepatitis B surface antibody [HBsAb] (except those with history of Hepatitis B vaccination, who will be included, if positive for HBsAb but negative for HBsAg and HBcAb), hepatitis C virus [HCV], or human immunodeficiency virus [HIV])
14.Patients with class III or IV heart failure (as defined by the New York Heart Association criteria) (New York Heart Association, 1994)
15.Patients with clinically significant abnormal electrocardiogram (ECG) findings
16.Patients with abnormal screening laboratory values:
•Hemoglobin ≤8 g/dL
•Platelet count ≤125,000/mm3
•White blood cell (WBC) count ≤3500/mm3
•Lymphocyte count ≤1000 cells/mm3
•Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT)/ Alkaline phosphatase (ALP) ≥3 × the upper limit of normal (ULN), or serum total bilirubin ≥2 × ULN
•Serum creatinine ≥2 mg/dL
17.Patients with active or prior history of clinically significant or uncontrolled respiratory, hepatic, renal, hematologic, gastrointestinal, endocrine, dermatologic, neurologic (including demyelinating disorders), metabolic, pulmonary, or cardiovascular diseases, or a history of any autoimmune disease or psychiatric illness, or any other condition which, in the opinion of the investigator, would jeopardize the safety of the patient or the validity of the study results
18.Patients who have participated in any other investigational study within 3 months prior to screening or are likely to simultaneously participate in another therapeutic clinical study
19.Pregnant females or nursing mothers
20.Females of childbearing potential and males who are not willing to use reliable and effective contraceptive measures during the course of the study
21.Patients receiving systemic/ intra-articular corticosteroids, excluding those receiving a ≤10 mg/day oral dose of prednisolone or equivalent corticosteroid, 2 weeks prior to screening
22.Patients who are receiving or who have received alkylating agents (e.g., cyclophosphamides) within 6 months prior to screening only if being received for conditions other than cancer (refer Exclusion criteria No. 7) or multiple sclerosis (prior history of either is a contraindication)
23.Patients who are using nonsteroidal anti-inflammatory drugs (NSAIDs) and are not on a stable dose within 2 weeks prior to screening
24.Patients determined by the investigator (or sub-investigator) to be ineligible for this study
25.Patients who have any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator, could affect the patient’s participation in the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Comparative safety assessment in terms of incidence of TEAEs including abnormal changes in laboratory parameters, vital signs and ECG that are clinically significant.
Up to 12 weeks
Secondary Outcome
Outcome
TimePoints
Proportion of patients with anti-etanercept antibodies (binding & neutralizing) following Etanercept administration.
at Day 1, Day 43 and Day 84
Assessment of usability experience based on changes in SIAQ® scores over time during the study.
Day 1, Day 22, Day 43, Day 64 and Day 78
Serum trough concentrations (Ctrough) at selected time points following Etanercept administration
at Day 1, Day 22, Day 43, Day 64 and Day 78
Target Sample Size
Total Sample Size="150" Sample Size from India="150" 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 multicentre, open label, randomized, comparative, sequential study in 150 patients with Rheumatoid Arthritis (RA). The study will be conducted in approximately 25 sites in India. The objective of the study to evaluate the safety of Enbrel®(reference product) in RA patients switched to YLB113 (test product biosimilar) as compared to Enbrel® AI continuation.