Clinical trial study to compare the effects of safety, drugs action of SAIT101 Verus MabThera Vs Rituxan in patients suffering from Rheumatoid Arthritis (Joint pain)

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2017/06/008758
• Date of registration: 05-06-2017
• Prospective Registration: Yes
• Primary sponsor: Archigen Biotech Limited
• Public title: Clinical trial study to compare the effects of safety, drugs action of SAIT101 Verus MabThera Vs Rituxan in patients suffering from Rheumatoid Arthritis (Joint pain)
• Scientific title: A Randomized, Double-blind, Parallel Group, Multicenter Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety, and Efficacy of SAIT101 versus MabThera® versus Rituxan® in Patients with Rheumatoid Arthritis (RA)
• Date of first enrolment: 19-06-2017
• Target sample size: 282
• Recruitment status: Not Yet Recruiting
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=18602
• Study type: Interventional
• Study design: Randomized, Parallel Group, Multiple Arm Trial; Method of generating randomization sequence:Other Method of allocation concealment:Centralized Blinding and masking:Participant, Investigator and Outcome Assessor Blinded
• Phase: Phase 3

Countries of recruitment

Bosnia and Herzegovina, Bulgaria, Czech Republic, Germany, Hungary, India, Italy, Mexico, Poland, Republic of Korea, Russian Federation, Spain, United States of America

Contacts

• Name: Suneela Thatte
• Affiliation: QuintilesIMS

• Name: Suneela Thatte
• Affiliation: QuintilesIMS

Key inclusion & exclusion criteria

Inclusion criteria: Diagnosis of RA according to ACR criteria for classification of RA for atleast 3 months prior to screening visit. And swollen joints and tended/painful joints from 66/68 joint count system. C reactive protein 1.0mgdL or an ESR28mmhr at screening. positive RF 20ml or antiCCP antibodies 10ml at screening. Patients with severe RA who have had an inadequate response to atleast 3 months treatment according to the approved treatment and dosage or intolerance to antiTNF therapy.

Cuurent treatment for RA on outpatient basis. Receiving MTX 7.5-25mgweek for atleast 12 weeks including the last 4 weeks prior to day 1 at a stable dose via the same route of administration dose and formulation. patients receiving a lower dose of MTX 10mgweek stable for 4 weeks prior to day 1 should be doing so as a result of a documented evidence of intolerance to higher doses of MTX. Lefluomide must be withdrawn atleast 12 weeks prior to day 1 or a minimum of 4 weeks prior to day 1if after 11 days of standaed cholestyramine washout. All DMARDS different from MTX and leflunomide must be withdrawn atleast 4to8 weeks. if receiving current treatment with oral corticosteroids, the dose must not exceed 10mg prednisone or equi. during the 4weeks prior to day 1 the dose must be stable. the most recent IM/intraarticular steroid injection should be prior to day1. If reciveing current treatment with NSAIDs at the time of screening, the patient must remain on a stable dose for atleast 3 weeks prior to day 1. Patient are willing to receive oral folic or folinic acid during the entire study mandatory co-medication for MTX treatment. according to local standards and avail. men and women of childbearing potential musy use 2 forms of accepted and highly effective methods of contraception during the course of the treatment period and for atleast 12 months after the last infusion of study drug. a man or women is childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active. eg of effective contraception include; estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation; oral, intravaginal, transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation 1 oral, injectable, implantable IUD, IUS bilateral tubal occlusion, vasectomized partner, sexual abstinence. Hormonal contraception maybe susceptible to interaction with the study drug, which may reduce the efficacy of the contraception method. vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the study participant and that the casectomised partner has received medical assessment of the surgical success. in the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from hetrosexual intercourse during the entire period of risk associated with the study treatments. the reliability of sexual abstinence needs to be evaluated in relation to the duration of the CT and the preferred and usual lifestyle of the subject. Female patients of childbearing potential must have a negative serum pregnancy test at screening visit 1. and a negative urine pregnancy test at each applicable visit thereafter. females will be considered to be of non childbearing potential if they fulfill one of the following criteria at screening. postmenopausal defined as amenorrheic for atleast 12 mont
Exclusion criteria: Females who are pregnant, breastfeeding, or planning a pregnancy during the treatment period of and 12 months after the last infusion of study drug. Class IV as per classification of Global Functional status in RA or wheelchair/ bedbound

History of or current inflammatory joint disease other than RA including but not limited to gout, reactive arthritis, psoriatic arthritis, seronegative spondyloathropathy or Lyme disease. History of or current systemic autoimmune disorder incl but not limited to systemic lupus erythematosus, inflammatory bowel disease, pulmonary fibrosis, felty syndrome, scleroderma, inflammatory myopathy, fibromyalgia, juvenile idiopathic arthiritis, mixed connective tissue disease, vasculitis or other overlap syndrome with the exception of the secondary Sjogren syndrome. Primary or secondary immunodeficiency virus (HIV) infection or positive test at screening. History of opportunistic infection. History of Deep space tissue infection fasciitis, abscess, osteomyelitis and infected prosthetic joint. Active infection of any kind or any major episode of infection requiring hospitalization or treatment with I.V anti-infective agents within 4 weeks prior to screening or oral anti infective agents within 2 weeks prior to sceening or use of antibiotic therapy three or more times in the last months prior to screening. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody or hepatitis C serology. Patients with a negative HBsAG and positive HBcAb must have a hepatitis B virus HBV deoxyribonucleic acid DNA level by polymerase chain reaction. These HBV patients must be willing to undergo monthly PCR HBV DNA testing treatment and may participate following consultation with a hepatitis expert regarding monitoring and use of HBV antiviral therapy and provided they agree to receive treatment as indicated. An HBV re-test will be performed monthly including Day 1, weeks 4,8,12,16,20,24,36,52 and unscheduled visit if required. patients with a positive test because of HBV vaccine maybe included i.e anti HB pos and anti HBc neg. Patients positive for hepatitis C virus HCV antibody are eligible only if PCR is negative for HCV ribonucleic acid RNA. Confirmed current active TB patients with latent TB as determined by positive QuantiFERON-TB test may be enrolled if such patients have written conformation from health care provider of adequate prophylaxis before or within the screening period and no evidence of tuberculosis on a chest X-ray performed within 3 months from day1. History of moderate to severe COPD and/or history of severe COPD exacerbation within the last 12 months of screening. Vaccination with live or attenuated vaccines within 6 weeks prior to first dose of study drug or planned administration during study participation or within 4 weeks following discontinuation of study drug. Treatment with IV Gamma Globulin or Prosorba column within 6months prior to day 1. History of server allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including hypersensitivity to any component of the study drug including unknown hypersensitivity or allergy to murine product. Hypogammaglobulinemia at screening 600 and less.

Patients with less than 8.5dL AND <1500 cells or platelet cound 75000 at screening if a patient has findings marginally below this limit re-testing is allowed at the investigators discretion within

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Rheumatoid Arthritis Health Condition 2: M069- Rheumatoid arthritis, unspecified

Intervention(s)

Intervention1: SAIT101: 1,000 mg (10 mg/mL) for i.v. infusion.
In Part A, each patient will receive one course of two 1,000 mg study drug infusions: one infusion on Day 1 and the second on Day 15.
In Part B, patients with an inadequate response (50% improvement from Baseline in swollen and tender joint counts at Week 24 [Visit 12]) will be eligible for a further course of two 1,000 mg drug infusions: one infusion at Week 24 and the second one at Week 26:
â?¢ Eligible patients in the SAIT101 arm will receive additional SAIT101 treatment at Week 24 and Week 26.
Control Intervention1: MabThera: 1000 mg (10 mg/ mL): 1,000 mg (10 mg/mL) MabThera® for i.v. infusion.In Part A, each patient will receive one course of two 1,000 mg study drug infusions: one infusion on Day 1 and the second on Day 15.
In Part B, patients with an inadequate response (50% improvement from Baseline in swollen and tender joint counts at Week 24 [Visit 12]) will be eligible for a further course of two 1,000 mg drug infusions: one infusion at Week 24 and the second one at Week 26:
� Eligible patients in the MabThera® arm will receive additional MabThera® treatment at Week 24 and Week 26.
Control Intervention2: Rituxan®: 1,000 mg (10 mg/mL): 1,000 mg (10 mg/mL) SAIT101 or Rituxan® or MabThera® for i.v. infusion.
In Part A, each patient will receive one course of two 1,000 mg study drug infusions: one infusion on Day 1 and the second on Day 15.
In Part B, patients with an inadequate response (50% improvement from Baseline in swollen and tender joint counts at Week 24 [Visit 12]) will be eligible for a further course of two 1,000 mg drug infusions: one infusion at Week 24 and the second one at Week 26:
� Eligible patients in the Rituxan® arm will be randomized in a 1:1 ratio to receive SAIT101 o

Primary Outcome(s)

compare the pharmacokinetics (PK) of SAIT101 VS MabThera® versus Rituxan® in patients with(RA)

Area under the conc-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t)

AUC from time 0 to infinity (AUC0-â??) AUC from time 0 to Day 15 prior to infusion(AUC0-d15)Maximum concentration (Cmax) after Day 15 infusion

Trough concentration (Ctrough) before the second infusion on Day 15

Main Efficacy Endpoints

Change from Baseline in DAS28 at Week 24Timepoint: compare the pharmacokinetics (PK) of SAIT101 VS MabThera® versus Rituxan® in patients with(RA)

Area under the conc-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration (AUC0-t)

AUC from time 0 to infinity (AUC0-â??) AUC from time 0 to Day 15 prior to infusion(AUC0-d15)Maximum concentration (Cmax) after Day 15 infusion

Trough concentration (Ctrough) before the second infusion on Day 15

Main Efficacy Endpoints

Change from Baseline in DAS28 at Week 24

Secondary Outcome(s)

The secondary objectives of the study are to compare the safety, additional PK, pharmacodynamics (PD), efficacy, tolerability, and immunogenicity of SAIT101 versus MabThera® versus Rituxan® in patients with rheumatoid arthritis (RA)Timepoint: Secondary PK Endpoints

AUC from Week 2 to Week 24(AUCw2-w24)

AUC from time 0 (immediately predose on Day 1) to Week 12 (AUC0-w12)Time of maximum concentration (Tmax) post infusion on Day 15

Secondary ID(s)

AGB 001 Version 3.1 dated 24 June 2016

Source(s) of Monetary Support

Archigen Biotech Limited 1 Francis Crick Avenue Cambridge Biomedical Campus, Cambridge CB2 0AA, United Kingdom

Secondary Sponsor(s)

Quintiles Research India Private Limited

Ethics review

Status: Approved
Approval date: 10/12/2016
Contact:

Ethics Committee Jehangir Clinical Development Centre Pvt. Ltd

Status: Approved
Approval date: 24/12/2016
Contact:

Ethics Committee MS Ramaiah Medical College and Hospitals

Status: Approved
Approval date: 29/12/2016
Contact:

Ethics Committee HRMC Cardiovascular Science & Research S.P. Medical College

Status: Approved
Approval date: 11/01/2017
Contact:

Sushruta Hospitals Ethics Committee

Status: Approved
Approval date: 17/01/2017
Contact:

Fortis Hospital Ethics Committee

Status: Approved
Approval date: 25/01/2017
Contact:

O & P Institutional Ethics Committee

Status: Approved
Approval date: 29/07/2017
Contact:

S. R. Kalla Memorial Ethical Committee for human Research

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee of B.J. Government Medical College & Sassoon General Hospital