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CTRI Number  CTRI/2020/09/028070 [Registered on: 28/09/2020] Trial Registered Prospectively
Last Modified On: 20/12/2021
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 study the safety and efficacy of Biosimilar Adalimumab injection versus HUMIRA® in subjects with active Ankylosing spondylitis . 
Scientific Title of Study   A prospective, multicenter, randomized, double blind, Phase III study to compare the efficacy and safety of Biosimilar Adalimumab injection of Enzene Biosciences Ltd. with HUMIRA® (adalimumab) injection in subjects with active Ankylosing spondylitis (AS).  
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
ALK20/ENZ129-ADA1 Version 2.0, 27/Jan/2020  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Akhilesh Sharma 
Designation  President & CMO 
Affiliation  Alkem Laboratoroes Limited 
Address  Alkem Laboratories Limited, Alkem House, Devashish, Adjacent to Matulya centre, Senapati Bapat Marg, Lower Parel

Mumbai
MAHARASHTRA
400013
India 
Phone    
Fax    
Email  akhilesh.sharma@alkem.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Vinayaka Shahavi 
Designation  Associate General Manager - Clinical Research 
Affiliation  Alkem Laboratoroes Limited 
Address  Alkem Laboratories Limited, Alkem House, Devashish, Adjacent to Matulya centre, Senapati Bapat Marg, Lower Parel

Mumbai
MAHARASHTRA
400013
India 
Phone    
Fax    
Email  vinayaka.shahavi@alkem.com  
 
Details of Contact Person
Public Query
 
Name  Dr Vinayaka Shahavi 
Designation  Associate General Manager - Clinical Research 
Affiliation  Alkem Laboratoroes Limited 
Address  Alkem Laboratories Limited, Alkem House, Devashish, Adjacent to Matulya centre, Senapati Bapat Marg, Lower Parel

Mumbai
MAHARASHTRA
400013
India 
Phone    
Fax    
Email  vinayaka.shahavi@alkem.com  
 
Source of Monetary or Material Support  
Alkem Laboratories Limited, Alkem House, Senapati Bapat Marg,Lower Parel, Mumbai – 400013, Maharashtra 
Enzene Biosciences Limited, Plot No. 165/1/26, Block T, Bhosari MIDC Area, Pune-411057,Maharashtra 
 
Primary Sponsor  
Name  Enzene Biosciences Limited 
Address  Enzene Biosciences Limited, Plot Number 165/1/26, Priyadarshani Society, Next to Gujjar Bharath gas) T 26, Internal Rd, MIDC, Bhosari, Pune, Maharashtra 411026 
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
Alkem Laboratories Limited   ALKEM HOUSE, “Devashish”, Adjacent to Matulya centre, Senapati Bapat Marg, Lower Parel west, Mumbai 400013 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 29  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Gaurav Seth  Akash Healthcare Super Specilaity Hopsital  Department of clinical research, Block no. 1, Akash Healthcare Super Specilaity Hospital, Hospital Road, Road No. 201, Dwarka Sector- 3, New Delhi- 110075
New Delhi
DELHI 
9871446609

gauravmarch18@gmail.com 
Dr Sujit Kumar Tripathy  All India Institute of Medical Sciences Bhubaneswar  Department of Orthopedics, All India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar, Odisha 751019
Khordha
ORISSA 
9438884155

ortho_sujit@aiimsbhubaneswar.edu.in 
Dr Uma Kumar  All India Institute of Medical Sciences, Delhi  Room No 4076, 4th Floor, Teaching Block, All India Medical Sciences, New Delhi
New Delhi
DELHI 
9868217040

umaakumar@yahoo.co.in 
Dr Mithun C B  Amrita Institue of Medical Science and Resrach Centre  Room no.1, Department of Rheumatology and Clinical Immunology, Amrita Institute of Medical Sciences, AIMS Ponekkara, Kochi- 682041, Kerala
Ernakulam
KERALA 
9442361893

mithuncb21886@aims.amrita.edu 
Dr A Ramakrishnam Naidu  Andhra Medical College, King George Hospital, Visakhapatnam  Department of Medicine, Andhra Medical College, King George Hospital, Maharanipeta, Visakhapatnam
Visakhapatnam
ANDHRA PRADESH 
9885093386

rammky@yahoo.com 
Dr Vishnu Sharma  Avron Hospital  Clinical Research Room, Department of Clinical Research, Avron Hospitals Pvt. Ltd., 4, Shantiniketan Park, Near Sardar Patel Colony, Ahmedabad, Gujarat 380013
Ahmadabad
GUJARAT 
8511555477

drvishnusharma@yahoo.co.in 
Dr Piyush Joshi  B J Medical College and Civil Hospital  B J Medical College and Civil Hospital, 2nd floor, Department Orthopedic, Asarwa, Ahmedabad- 380016
Ahmadabad
GUJARAT 
8879102056

pnjoshi2005@gmail.com 
Dr Chandrashekara Srikantiah  Chanre Rheumatology and Immunology Centre and Research  Chanre Rheumatology and Immunology Centre and Research, No. 65 (414), 20th Main, 1st Block, West of Chord Road, Rajaji Nagar, Bengaluru, Karnataka 560010
Bangalore
KARNATAKA 
08042516635

chanrericr@yahoo.co.in 
Dr John Mathew  Christian Medical College  Room no. 900A, Department of Clinical Immunology and Rheumatology, West block building, Christian Medical College, VELLORE, Tamil Nadu- 632004
Vellore
TAMIL NADU 
041-62283537

johnmathew@cmcvellore.ac.in 
Dr Sajal Mitra  Government Medical College and Hospital  Ward No. 17, Department Of Orthopedics, Government Medical College and Hospital, Medical College Square, Nagpur- 440003
Nagpur
MAHARASHTRA 
9373114929

sajalmitra2007@yahoo.co.in 
Dr Jyoti Ranjan Parida  Institute of Medical Science and SUM Hospital  Institute of Medical Science and SUM Hospital, Room no. 71 (OPD), Department of Immunology and Rheumatology, New Extension Building,Super speciality Division, K8 Lane 1, Kalinga Nagar, Bhubaneswar, Odisha 751003
Khordha
ORISSA 
9556980101

drjrparida@gmail.com 
Dr Saurabh Singh  Institute of Medical Sciences, Banaras Hindu University  4th floor, Department of Orthopaedic, Institute of Medical Sciences, Banaras Hindu University, Varanasi- 221005
Varanasi
UTTAR PRADESH 
9838759998

saurabhrpsingh@gmail.com 
Dr Chengappa K G  Jawaharlal Institute of Postgraduate Medical Education, Puducherry  Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education, Jipmer Campus Rd, Gorimedu, Dhanvantari Nagar, Puducherry, 605006
Pondicherry
PONDICHERRY 
04132297356

doc.chengappa@gmail.com 
Dr Rajeshwar Nath Srivastava  King Georges Medical University  Department of Orthopedic surgery, King Georges Medical University, 9-Nabiullah Road, Lucknow 226003
Lucknow
UTTAR PRADESH 
9415054330

drrnsrivastava@gmail.com 
Dr Kaushik Basu  Medical College and Hospital, Kolkata  OPD, Department of Medicine, Medical College and Hospital, 88 College street, Kolkata- 700073
Kolkata
WEST BENGAL 
9038831211

phoenix.0013@gmail.com 
Dr Girish Bhatia  Medipoint Hospitals Pvt. Ltd.  Medipoint Hospitals Pvt. Ltd., 241/1, New D P Road, Aundh, Pune- 411007
Pune
MAHARASHTRA 
7387003636

drbhatia.pentagon@gmail.com 
Dr Chethana Dharmapalaiah  Medstar Speciality Hospital,   Medstar Speciality Hospital, Research Department, 5th Floor, 641/17/1/3, Kodigehalli Main Road, Sahakarnagar, Bangalore-560092, Karnataka, India
Bangalore
KARNATAKA 
966334422

drchethanamedstar@gmail.com 
Dr Susheel Kumar  Nehru Hospital, Postgraduate Institute of Medical Education & Research  Department of Internal Medicine, Nehru Hospital, Postgraduate Institute of Medical Education & Research, Sector 12, Chandigarh 160012
Chandigarh
CHANDIGARH 
7087008184

susheelbhutungru@gmail.com 
Dr Bankim Desai  Nirmal Hospital  Nirmal Hospital, Ring Road, Surat- 395002, Gujarat
Surat
GUJARAT 
9825136077

drbankimd@gmail.com 
Dr Girish Kakade  Sahyadri Superspeciality hospital  Sahyadri Superspeciality Hospital, Room no. 21, Department of Orthopedic, 30-C, Erandwane, Karve Road, Pune- 411004
Pune
MAHARASHTRA 
020-67213000

drgirishkakade@gmail.com 
Dr Ajit Nalawade  Sancheti Institute for Orthopaedics and Rehabilitation  Department of Rheumatology, Sancheti Institute for Orthopaedics and Rehabilitation, 16,Shivajinagar, Pune 411005, Maharashtra
Pune
MAHARASHTRA 
02041236660

dr.ajitnalawade@gmail.com 
Dr Archana Sonawale  Seth G.S. Medical College and KEM Hospital  Seth G.S. Medical College and KEM Hospital, 1st floor, Department of pharmacology and Therapeutics, College Building, Acharya Donde Marg, Parel East, Parel, Mumbai, Maharashtra 400012
Mumbai
MAHARASHTRA 
9892639939

archanasonawale@kem.edu 
Dr Reena Sharma  Shalby Hospitals  Shalby Hospitals, Opp. Karnavati Club, S G Highway, Ahmedabad 380015
Ahmadabad
GUJARAT 
9924957400

reena141@gmail.com 
Dr Neeraj Jain  Sir Ganga Ram Hospital  Clinical research room, Department of clinical research, 1 floor , near HDU, Department of Rheumatology and Clinical Immunology, Sir Ganga Ram Hospital, SGRH marg, Rajinder Nagar, New Delhi- 110060
New Delhi
DELHI 
9810130150

neerajrheumatology@gmail.com 
Dr Raman Sharma  SMS Medical College and Hospital  Main Building Second floor, Department of Medicine, Division of general medicine, SMS Medical College & Attached Hospital’s, J.L.N. Marg, Jaipur- 302001, Rajasthan
Jaipur
RAJASTHAN 
9414044488

sharmarm@gmail.com 
Dr Sankaralingam Rajeshwari  Sri Ramachandra Institute of Higher Education and Research  Department of rheumatology, Sri Ramachandra Institute of Higher Education and Research, No.1, Ramachandra Nagar, Porur, Chennai, Tamil Nadu 600116
Chennai
TAMIL NADU 
9444174759

calling_raji@yahoo.com 
Dr Firdusa Fatima  St Theresa’s Multi Specialty Hospital  Department of Clinical Research, 1st floor, Krupa Ward, St Theresa’s Multi Specialty Hospital, Erragadda Main Rd, opposite Erragadda Rythu Bazar, Jet Colony, Sanath Nagar, Hyderabad, Telangana 500018
Hyderabad
TELANGANA 
4023704411

drfirdusafatima@gmail.com 
Dr Vikram Haridas  Sushruta Multispeciality Hospital & Research Centre Private Limited  Sushruta Multispeciality Hospital & Research Centre Private Limited., #313, 314, Old delux ward, Sushrutha Hospital, P B Road, Vidyanagar, Hubali- 580021, Karnataka
Dharwad
KARNATAKA 
09379542888

haridasvikram@yahoo.co.in 
Dr Romi Shah  Tristar Hospital  Tristar Hospital, opp. T & TV High School, Athwa Gate, Surat, Gujarat 395001
Surat
GUJARAT 
8238004052

drshahromi@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 29  
Name of Committee  Approval Status 
Avron Multi speciality Hospital, Ethics Committee  Approved 
Ethics Committee, IMS & SUM Hospitals, Orissa  Approved 
Ethics Committee, Sir Ganga Ram Hospital  Approved 
Ethics Committee, St. Theresas Hospital, Hyderabad  Approved 
Institutional Ethics Commitee, KGMU, UP  Approved 
Institutional Ethics Committee B J Medical College & Civil Hospital  Submittted/Under Review 
Institutional Ethics Committee for Human research, Kolkata  Approved 
Institutional Ethics committee Sancheti Institute, Pune  Approved 
Institutional Ethics Committee, AIIMS, Delhi  Approved 
Institutional Ethics Committee, Akash Healthcare, Delhi  Approved 
Institutional Ethics Committee, Amrita Institute of Medical Sciences  Approved 
Institutional Ethics Committee, Andhra Medical College, Visakhapatnam   Approved 
Institutional Ethics committee, ChanRe Rheumatology and Immunology Center, Beglore  Approved 
Institutional Ethics Committee, Government Medical College and Hospital, Nagpur  Submittted/Under Review 
Institutional Ethics Committee, IMS BHU  Submittted/Under Review 
Institutional Ethics Committee, JIMPER, Puducherry  Submittted/Under Review 
Institutional Ethics Committee, PGI, Chandigarh  Submittted/Under Review 
Institutional Ethics Committee, Seth GS Medical College and KEM Hospital  Approved 
Institutional Ethics Committee, SRIHER, Chennai  Submittted/Under Review 
Institutional Etihcs Committee, AIIMS, Bhubneshwar  Submittted/Under Review 
Medstar Speciality Hospital Ethics Committee, Bengalore  Approved 
Nirmal Hospital Ethics Committee, Surat  Approved 
Office of Research Institutional Review Board, Christian Medical College  Approved 
Office of the ethics committee, SMS Medical College & Attached Hospitals  Submittted/Under Review 
Penta-Med Ethics Committee  Approved 
Sahyadri Hospital Ltd., Ethics Committee  Approved 
Sushrutha Hospital Ethics Committee, Huballi  Approved 
The Shalby Limited, Ahmedabad  Approved 
Tristar Hospital EThics Committee, Surat  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: M459||Ankylosing spondylitis of unspecified sites in spine,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Biosimilar Adalimumab injection  40 mg/0.4 mL, single-use glass vial, for subcutaneous use of Enzene Biosciences Ltd. 
Comparator Agent  Innovator Adalimumab (HUMIRA®)   40 mg/0.4 mL, single-use glass vial, for subcutaneous use of AbbVie Inc 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  65.00 Year(s)
Gender  Both 
Details  1. Male or Female subjects between 18 to 65 years of age
2. Subjects with diagnosis of Axial Ankylosing spondylitis based on the 1984 modified New York classification criteria, has active AS, as defined by fulfillment of at least 2 of the following 3 conditions at both Screening and Baseline visits:
a. BASDAI score ≥ 4
b. Total back pain on a visual analog scale ≥ 4
c. Morning stiffness ≥ 1 hour
4. Has inadequate response to or intolerance to one or more non-steroidal anti-inflammatory drugs (NSAIDs) as assessed by the Investigator
5. Willing and able to comply with the protocol. Willing and able to comply with the protocol.  
 
ExclusionCriteria 
Details  1. Has total spinal ankylosis
2. Has undergone spinal surgery or joint surgery involving joints assessed within 2 months prior to screening
3. Has received intra-articular joint injection(s), spinal or paraspinal corticosteroid injection(s) within 28 days prior to Baseline
4. Has prior exposure to any anti-TNF therapy at any time
5. Subjects with clinically active TB
6. Subjects with underlying conditions that may predispose them to infection
7. Subjects with history or presence of cardiac, renal, neurologic, psychiatric, endocrinologic, metabolic, or hepatic disease which in the opinion of the investigator does not allow participation of the subject in this study
8. Known hypersensitivity to any component of the investigational product and other medications used in this study
9. Subjects with a non-healed fracture
10. Subject’s having the following laboratory results at screening
a. Absolute neutrophil count (ANC) < 1,500/mm3 b. Hemoglobin (Hb) <10 g/dL
c. Platelet count < 100,000/mm3
d. Total bilirubin level > 1.5 times the upper limit of the normal laboratory range (ULN)
e. AST and ALT >3 x ULN
f. Alkaline phosphatase >3 x ULN
g. Serum Creatinine level > 1.25 xULN
11. Subjects suffering from acute or chronic infection(s)
12. Subjects with congestive heart failure
13. Positive serology for human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) at screening
14. Subjects of child bearing potential, who are not willing to use adequate contraception during the study period.
15. Female subjects who are pregnant or nursing
16. Has any concurrent disease or condition, which in the opinion of the investigator does not allow participation of the subject in this study
17. Has participated in any other clinical trial and received experimental medications within 4 weeks prior to screening  
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
To compare the efficacy of Biosimilar Adalimumab injection with HUMIRA® (adalimumab) injection, in subjects with active Ankylosing spondylitis (AS) by assessment of ASAS20 response criteria   All subject completing till week 12 
 
Secondary Outcome  
Outcome  TimePoints 
1. Pharmacokinetics (PK) of Biosimilar versus HUMIRA® (adalimumab) injection
2. Immunogenicity of Biosimilar and HUMIRA® (adalimumab) injection by assessment of anti-Adalimumab antibody
3. Safety and tolerability of the investigational product  
1. All subject completing till week 12
2. Subject completing pK assessment at baseline
3. Subject completing immunogenicity assessment at baseline, Week 6 and 12. 
 
Target Sample Size   Total Sample Size="192"
Sample Size from India="192" 
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="0" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   15/10/2020 
Date of Study Completion (India) Date Missing 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="1"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   NIL 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   A prospective, multicenter, randomized, double blind, Phase III study to compare the efficacy and safety of Biosimilar Adalimumab injection of Enzene Biosciences Ltd. with HUMIRA® (adalimumab) injection in subjects with active Ankylosing spondylitis (AS). 

Primary Objective:  To compare the efficacy of Biosimilar Adalimumab injection with HUMIRA® (adalimumab) injection, in subjects with active Ankylosing spondylitis (AS) by assessment of ASAS20 response criteria 
 
Secondary Objective(s): 

To evaluate the following: 1. Pharmacokinetics (PK) of Biosimilar versus HUMIRA® (adalimumab) injection 
2. Immunogenicity of Biosimilar and HUMIRA® (adalimumab) injection by assessment of anti-Adalimumab antibody 
3. Safety and tolerability of the investigational product
 
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