CTRI/2017/03/008063 [Registered on: 10/03/2017] Trial Registered Retrospectively
Last Modified On:
22/03/2019
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Randomized, Parallel Group Trial
Public Title of Study
To compare the efficacy and safety of BCD-055 (CJSC BIOCAD, Russia) and Remicade® with methotrexate in patients with rheumatoid arthritis
Scientific Title of Study
International comparative multicenter double-blind randomized clinical study of efficacy and safety of BCD-055 (CJSC BIOCAD, Russia) and Remicade® in combination with methotrexate in patients with active rheumatoid arthritis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
BCD-055-3/LIRA Version 1.1 dated 17.03.2016
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Mrutyunjaya Ganiger
Designation
Project Manager - Clinical Trials
Affiliation
BIOCAD INDIA PVT LTD
Address
BIOCAD INDIA PVT LTD,
163/C, 3rd Cross, 3rd Phase, J.P.Nagar,
Bangalore
KARNATAKA
560078
India
Bangalore KARNATAKA 560078 India
Phone
8123000277
Fax
Email
mrutyunjaya.g@biocadindia.com
Details of Contact Person Scientific Query
Name
Dr Mrutyunjaya Ganiger
Designation
Project Manager - Clinical Trials
Affiliation
BIOCAD INDIA PVT LTD
Address
BIOCAD INDIA PVT LTD,
163/C, 3rd Cross, 3rd Phase, J.P.Nagar,
Bangalore
KARNATAKA
560078
India
Bangalore KARNATAKA 560078 India
Phone
8123000277
Fax
Email
mrutyunjaya.g@biocadindia.com
Details of Contact Person Public Query
Name
Dr Mrutyunjaya Ganiger
Designation
Project Manager - Clinical Trials
Affiliation
BIOCAD INDIA PVT LTD
Address
BIOCAD INDIA PVT LTD,
163/C, 3rd Cross, 3rd Phase, J.P.Nagar,
Bangalore
KARNATAKA
560078
India
2nd floor, Medical Research Department, Rao Saheb Achutrao, Patwardhan Marg, Four Bunglows, Andheri West, Mumbai, Maharashtra 400053 Mumbai MAHARASHTRA
9321542959
sunilkumar.r.singh@relianceada.com
Dr Syamasis Bandyopadhyay
Apollo Gleneagles Hospitals
1st floor, clinical research department, 58, Canal Circular Road, Kadapara, Kolkata, West Bengal 700054 Kolkata WEST BENGAL
09836576602
sambando@yahoo.co.uk
Dr Kartikeya Parmar
B.J. Medical College & Civil Hospital
Department of Medicine
New Civil Hospital, Haripura, Asarwa, Ahmedabad, Gujarat 380016 Ahmadabad GUJARAT
09924643799
drkartik@gmail.com
Dr Nagnath K Redewad
B.J. Medical College & sasoon General hospital
Department of medicine
B.J. Govt. Medical College & Sassoon General Hospital,
Jai Prakash Narayan Road, Near Pune Railway Station, Pune, Maharashtra 411001 Pune MAHARASHTRA
Ethics Commitee - S.P Medical College & AG of Hospitals
Approved
Ethics committee - Institute of medical Science IMS and SUM Hospital
Approved
Ethics Committee - Shalby Hospital
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee - Government medical college and Sasoon general hospital
Approved
Institutional Ethics Committee - NRS medical college
Approved
Institutional Ethics Committee, Apollo Gleneagles Hospital
Approved
Institutional Ethics Committee, Noble hospital
Approved
Institutional Ethics Committee,Sapthagiri Institute of medical science and research center
Approved
Institutional Ethics Committee- Government medical college, Nagpur
Approved
Institutional Ethics Committee- medical college kolkata
Approved
Institutional Scientific and Ethics Board
Approved
NIMS Institutional ethic commiteee
Approved
Poona Medical Research Foundation, Institutional Ethics Commitee
Approved
The Institutional Ethics Committee - B.J Medical College and Civil hospital, Ahmedabad
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
No Objection Certificate
Health Condition / Problems Studied
Health Type
Condition
Patients
Patients with diagnosis of active rheumatoid arthritis ,
Intervention / Comparator Agent
Type
Name
Details
Intervention
BCD-055-3(Infliximab manufactured by CJSC BIOCAD Russia)
In the study, after signing the Informed Consent and completing screening procedures, patients will be stratified and randomly assigned (randomized) to receive BCD-055 and the comparator drug in ratio of 2:1. Patients will be stratified according to Country of residence (CIS countries/other countries),Age (40/ ≥40 years),Degree of disease activity at the time of screening (moderate activity of the disease – 3.2 DAS28-CRP(4) ≤ 5.1/high disease activity DAS28-CRP(4) 5.1) and Applied methotrexate dose (less than 20 mg/25 mg and more. Patients will use BCD-055 in a dose of 3 mg/kg applied as a single 2-hour intravenous infusion on Day 1 of Week 0 (Visit 1), Day 1 of Week 2 (Visit 2), Day 1 of Week 6 (Visit 3) and then at intervals of 8 weeks (Weeks 14, 22, 30, 38, 46 and 54; Visits 4, 5, 6, 7, 8, 9)
In the study, after signing the Informed Consent and completing screening procedures, patients will be stratified and randomly assigned (randomized) to receive BCD-055 and the comparator drug in ratio of 2:1. Patients will be stratified according to Country of residence (CIS countries/other countries),Age (40/ ≥40 years),Degree of disease activity at the time of screening (moderate activity of the disease – 3.2 DAS28-CRP(4) ≤ 5.1/high disease activity DAS28-CRP(4) 5.1) and Applied methotrexate dose (less than 20 mg/25 mg and more. Patients will use Remicade in a dose of 3 mg/kg applied as a single 2-hour intravenous infusion on Day 1 of Week 0 (Visit 1), Day 1 of Week 2 (Visit 2), Day 1 of Week 6 (Visit 3) and then at intervals of 8 weeks (Weeks 14, 22, 30, 38, 46 and 54; Visits 4, 5, 6, 7, 8, 9).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Signed informed consent to participate in the study;
2. Men and women aged 18-75 years inclusive;
3. Confirmed diagnosis of rheumatoid arthritis according to ACR criteria 2010 set at least 6 months prior to screening;
4. Active rheumatoid arthritis at the time of screening despite methotrexate therapy which lasted for the past 3 months;
5. The use of methotrexate in a stable dose for the past 4 weeks prior to the screening period (15-25 mg range per week);
6. Ineffectiveness of previous therapy by disease-modifying antirheumatic drugs (including methotrexate);
7. Consent of a patient with preserved childbearing potential during the period of study to use reliable methods of contraception40 from the date of IC signature and up to 8 weeks after the last dose of study drug/comparator;
8. Adequate kidney and liver function determined at screening under the following parameters:
a. Serum creatinine ≤ 1.2mg/dL for females, ≤ 1.4mg/dL for males or creatinine clearance> 75 ml/min;
b. ALT level ≤ ULN adopted in the center laboratory;
c. AST level ≤ ULN adopted in the center laboratory.
9. Absence of clinically significant abnormalities in complete blood count conducted at screening, determined as:
a. Hemoglobin level ≥120 g/l for males and ≥100 g/l for females;
b. White blood cell count ≥3.5 × 109/l;
c. Absolute neutrophil count ≥1.5 × 109/l;
d. Platelet count ≥100 × 109 platelets/l.
10. Ability of the patient to follow the protocol procedures, according to the investigator.
ExclusionCriteria
Details
1. Prior use of any products based on monoclonal antibodies (including tumor necrosis factor alpha inhibitors) for the treatment of rheumatoid arthritis;
2. Felty’s syndrome (irrespectively to clinical form);
3. Functional status of the patient - Class IV according to ACR 1991 classification;
4. Low activity of rheumatoid arthritis (according to DAS28-CRP(4) index of less than 3.2 points);
5. The use of the following medicinal products as concomitan therapy
The need for administration of prednisolone or its equivalent in a dose of more than 10 mg orally daily;
a. The need for oral administration of prednisone or its equivalent in a dose of ≤10 mg daily, if the dose was not stable for the last 4 weeks before infliximab therapy (it is permitted to include the patients receiving topical glucocorticosteroids);
b. The use of other disease-modifying antirheumatic drugs besides methotrexate, including hydroxychloroquine, chloroquine, sulfasalazine within 4 weeks prior to screening. If a patient took leflunomide, his screening period should be extended to 12 weeks during which leflunomide administration is prohibited (washout period);
c. Acceptance of alkylating agents at any time during 12 months before screening;
d. Intra-articular administration of corticosteroids for less than 4 weeks prior to randomization;
e. Vaccination with live or attenuated vaccines at any time during the 8 weeks prior to screening.
6. Determined hypersensitivity to murine proteins or any components of the study drugs, methotrexate, folic acid, as well as the drugs being a part of premedication;
7. Hepatitis B, active hepatitis C, HIV, syphilis;
8. Determined diagnosis of tuberculosis;
9. Latent tuberculosis (positive Diaskintest®/PPD test with 5TU/QuantiFERON®-TB Gold test in the absence of pulmonary tuberculosis in the chest radiography). It is permitted to include the patients with suspicious Diaskintest®/PPD test with 5TU/QuantiFERON®-TB Gold test result after consulting with a phthisiatrician who confirmed that latent tuberculosis is absent in this patient;
10. The established diagnosis of other acute or severe chronic infection (sepsis, abscesses, invasive mycoses, histoplasmosis) at screening or in history;
11. Patients with the diagnosed bacterial infection that required oral administration of antibacterial drugs during the two weeks preceding the time of signing the informed consent; patients with the diagnosed bacterial infection that required parenteral administration of antibacterial drugs during four weeks prior to screening;
12. Patients with the established diagnosis of herpes zoster;
13. Drug abuse, alcoholism (including history);
14. Other documented diseases that increase the risk of adverse events in a patient during the study treatment or that mayaffect the assessment of symptoms of the underlying disease; mask, increase, modify the symptoms of the underlying disease or cause clinical, laboratory and instrumental symptoms similar to those of rheumatoid arthritis
15. Body mass of more than 130 kg;
16. Pregnancy, pregnancy planning less than 8 weeks after the end of participation in the study, breastfeeding.
17. Simultaneous participation in any other clinical trial, as well as former participation in other clinical trials within 3 months before this study initiation; previous participation in this study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Sequentially numbered, sealed, opaque envelopes
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Proportion of patients with rheumatoid arthritis in each group who achieve improvement in disease according to ACR20 at Week 14 from the time of the first infliximab infusion.
Week 14 from the time of the first infliximab infusion according to ACR20 criteria
1. At Weeks 30 and 54 from the time of the first infliximab infusion according to ACR20 criteria
2.At Weeks 14, 30 and 54 from the time of the first infliximab infusion according to ACR50/70 Criteria
3.Quality of life of patients before the therapy in 14, 30 and 54 weeks after the therapy according to SF36 survey
Target Sample Size
Total Sample Size="426" Sample Size from India="140" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
It is an International comparative multicenter double-blind randomized clinical study of efficacy and safety of BCD-055 (CJSC BIOCAD, Russia) and Remicade® in combination with methotrexate in patients with active rheumatoid arthritis, Phase III study. Patients of both genders aged 18 to 75 years inclusive, with diagnosis of active1 rheumatoid arthritis established at least 6 months prior to screening. the main objective is to establish the equivalence of efficacy and equal safety of BCD-055 and Remicade® when used in patients with active rheumatoid arthritis, Determine the proportion of patients in each group who reached 20%, 50% and 70% improvement in activity parameters of rheumatoid arthritis according to ACR criteria in 14, 30 and 54 weeks after start of therapy, Determine the proportion of patients in each group who reached remission and low disease activity according to DAS28-CRP (4), SDAI, CDAI criteria in 14, 30 and 54 weeks after start of therapy, Determine the proportion of patients in each group with persistent medium and high disease activity according to DAS28-CRP (4), SDAI, CDAI criteria in 14, 30 and 54 weeks after start of therapy, Determine the proportion of patients in each group with the appearance of binding antibodies to infliximab, as well as the number of cases of the appearance of neutralizing antibodies to infliximab. Identify the presence/absence of correlation between the development of immune response and drug efficacy, Determine the range, frequency and severity of adverse events in repeated administration of BCD-055 or Remicade® to patients with active rheumatoid arthritis.comparative evaluation of safety in patients with active rheumatoid arthritis. The statistical sample calculation showed that in order to prove the hypothesis of equivalence at α level of 0.05 and power of 80%, the study should include 140 patients (93 patients – into the main group, 47 patients – into the reference group).
After signing the informed consent to participate in the study and completion of all screening procedures, eligible patients will be stratified according to country of residence (CIS countries other countries), age (younger than 40 years, 40 years and older), degree of disease activity at the time of screening (moderate activity of the disease – 3.2 5.1) and applied methotrexate dose (less than 20 mg/25 mg and more), and then randomly assigned (randomized) into one of two groups in the ratio of 2:1.
All patients will additionally receive methotrexate in a stable dose of 15 to 25 mg per week orally or parenterally, as well as folic acid in a dose of 5 mg per week. The study will involve 10 visits, including 9 visits for study drug/comparator infusion.The participation of one patient in the study involves treatment and observation in the period from the beginning of screening to Visit at Week 58 (i.e., maximum 62 weeks).