CTRI/2016/05/006899 [Registered on: 05/05/2016] Trial Registered Prospectively
Last Modified On:
09/09/2017
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 study to compare the biosimilar of Etanercept (coded as YLB113) made by YLBiologics with Enbrel (originator’s Etanercept) in patients suffering from rheumatoid arthritis with respect to its efficacy, safety and antibody formation.
Scientific Title of Study
A Comparative Study to Assess the Efficacy, Safety and Immunogenicity
of YLB113 and Enbrel for the Treatment of Rheumatoid Arthritis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
NIL
NIL
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Shoaib Mohammad
Designation
Sr. Medical Director
Affiliation
Kendle India Private Limited
Address
Building No. 14, Tower-B, 14th Floor DLF Cyber City, Phase III
Gurgaon HARYANA 122001 India
Phone
01244642458
Fax
01244642401
Email
shoaib.mohammad@incresearch.com
Details of Contact Person Scientific Query
Name
Dr Shoaib Mohammad
Designation
Sr. Medical Director
Affiliation
Kendle India Private Limited
Address
Building No. 14, Tower-B, 14th Floor DLF Cyber City, Phase III
Gurgaon HARYANA 122001 India
Phone
01244642458
Fax
01244642401
Email
shoaib.mohammad@incresearch.com
Details of Contact Person Public Query
Name
Mamta Singh
Designation
Associate Director - SSU & RA
Affiliation
Kendle India Private Limited
Address
Building No. 14, Tower-B, 14th Floor DLF Cyber City, Phase III Gurgaon
Gurgaon HARYANA 122001 India
Phone
01244642449
Fax
01244642401
Email
mamta.singh@incresearch.com
Source of Monetary or Material Support
YL Biologics Ltd.
2-31-1,
Nihonbashi-Hamacho,
Chuo-ku,
Tokyo, 103-0007, Japan
Primary Sponsor
Name
YL Biologics Ltd
Address
2-31-1, Nihonbashi-Hamacho,
Chuo-Ku, Tokyo - 103-0007, Japan
AND
Lupin Limited ( Research Park),
46A/47A, Nande Village, Mulshi Taluka,
Pune-412115, Maharashtra, India
Type of Sponsor
Other [Pharmaceutical Company]
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Bulgaria Czech Republic Hungary India Latvia Poland Romania Russian Federation Spain Ukraine Japan
Artemis Health Sciences Institutional Ethics Committee
Approved
Ethics Committee - S.P.Medical College & AG of Hospitals
Approved
Ethics Committee Jehangir Clinical Development Centre Pvt. Ltd.
Approved
Ethics Committee, Sir Ganga Ram Hospital
Approved
Ethics Committee-Shalby Limited
Approved
Govt Medical College, Kozhikode, Institutional Ethics Committee
Approved
Institutional Ethics Committee of Postgraduate Institute of Medical Education and Research
Approved
Institutional Ethics committee,Govt. Medical College, Nagpur
Approved
Institutional Ethics Committee-BGS Global Hospitals
Approved
Institutional Ethics Committee-NIMS
Approved
Institutonal Ethics Committee, B.J. Medical College & Civil Hospital
Approved
Nirmal Hospital Pvt Ltd Ethics Committee
Approved
Penta-Med Ethics Committee
Approved
SR Kalla Memorial Ethical Committee For Human Research
Approved
Sushruta Hospitals Ethics Committee
Approved
Swastic Ethics Committee
Approved
Yash Society Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Patients with active RA despite treatment with a fixed dose of MTX,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Enbrel
Etanercept is a fusion protein produced by recombinant DNA technology in a Chinese hamster
ovary (CHO) mammalian expression system. Etanercept is a dimer of a chimeric protein
genetically engineered by fusing the extracellular ligand binding domain of human tumor necrosis factor receptor-2 (TNFR2) to the Fc domain of human IgG1.
Intervention
YLB113
YLB113 (developed by YL Biologics Co., Ltd. hereinafter referred to as YL Biologics Ltd.) is
an investigational biosimilar of Enbrel® (manufactured and marketed by Pfizer, Inc.
(hereinafter referred to as Pfizer Inc.)) which has the active ingredient Etanercept. YLB113 is
found to be equivalent in Phase 1 clinical studies in Japan & India.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
Stage A
Patients must meet the following criteria:
(1) Male or female adults more than or equal to 18 and less than or equal to 75 years of age at the time of informed consent.
(2) Patients diagnosed with RA according to the 2010 American College of Rheumatology
(ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA and are capable of providing written informed consent to participate in the study.
(3) Patients with more than or equal to 6 tender joints and more than or equal to 6 swollen joints (based on the Swollen Joint Count [SJC] using 66 joints and Tender Joint Count [TJC] using 68 joints) and a DAS28 score
more than or equal to 3.2.
(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 (6 - 25 mg/week [15 – 25 mg/week for India], not exceeding the local approved dose) that
has remained stable for at least 6 weeks prior to screening.
(6) Patients who have discontinued treatment with disease-modifying anti-rheumatic drugs
(DMARDs), other than MTX and complete a washout period of at least 2 weeks or at least five half-lives prior to drug administration, whichever is longer.
Stage B
(1) Patients who complete evaluations for Week 24 in Stage A and are willing to continue in Stage B.
(2) Patients without serious adverse events (SAEs) or unresolved Grade 3 or higher adverse
events related to the study drugs and who tolerated the study drugs administered in Stage A.
ExclusionCriteria
Details
Patients who meet any of the following criteria will be excluded from this clinical trial:
Stage A:
(1) Patients with known hypersensitivity to Etanercept or any other components of the YL Biologics Ltd.
(2) Patients allergic to latex (the needle cap on the Etanercept prefilled syringe 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 (and those with
positive test results for beta-D-glucan only for Japan) within 3 months prior to screening.
(4) Patients with active tuberculosis (TB), prior history of unsuccessfully treated TB,
latent TB, or those who are at risk of developing TB (e.g. those who were in contact
with patients of active TB in the recent past prior to screening) and patients who are
not negative for TB tests (e.g., T-SPOT® TB or QuantiFERON®-TB Gold test/ appropriate 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 a prosthetic joint.
(6) Patients diagnosed with other rheumatic diseases, autoimmune disease, connective
tissue disease, or immune deficiencies (e.g., 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 (except for successfully treated
non-metastatic basal or squamous cell carcinoma of the skin and carcinoma insitu 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 previously treated with any other biologic response modifiers for any
auto-immune indication (including but not limited to tocilizumab, adalimumab,
anakinra, abatacept, infliximab, rituximab, golimumab, etanercept, certolizumab and
tofacitinib).
(12) 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]).
(13) Patients with class III or IV congestive heart failure (as defined by the New York
Heart Association criteria) (New York Heart Association, 1994).
(14) Patients with clinically significant abnormal electrocardiogram (ECG) findings.
"Other standard Exclusion criteria are as per Protocol".
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
On-site computer system
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Stage A: ACR20 response rate at Week 24 of dosing.
24 weeks
Secondary Outcome
Outcome
TimePoints
Efficacy assessments:
- ACR20 response rate at Weeks4, 8 and 12 of dosing
- ACR50 response rate at Weeks 4, 8, 12 and 24of dosing
- ACR70 response rate at Weeks 4, 8, 12 and 24 of dosing
- An improvement in the DAS28 response rate at Weeks 4, 8,12 and 24 of dosing
- Safety assessments (Adverse events, Physical examination, vital signs, ECG, Clinical laboratory examination and Injection site assessment)
- Immunogenicity (at Weeks 4, 8, 12 and 24 of dosing)
Weeks 4, 8, 12 and 24
Target Sample Size
Total Sample Size="500" Sample Size from India="100" Final Enrollment numbers achieved (Total)= "471" Final Enrollment numbers achieved (India)="26"