Severe Rheumatoid Arthritis (RA) MedDRA version: 20.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870
Conditions
Interventions
Product Name: SAIT101 (proposed rituximab biosimilar)
Product Code: SAIT101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sp
Sponsors
Archigen Biotech Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Parts A and B: 1. Male or female outpatient, between 18 and 80 years of age at Screening 2. Severe RA defined as: - Diagnosis of RA according to the revised (1987) ACR criteria for the classification of RA for at least 3 months prior to screening visit. - And =6 swollen joints and =6 tender/painful joints (from the 66/68 joint count system) - And C-reactive protein (CRP) =1.0 mg/dL or an ESR =28 mm/hour at Screening - And positive RF (=20 units/mL) or anti-CCP antibodies (=10 units/mL) at Screening 3. Patients with severe RA who have had an inadequate response to at least 3 months’ treatment (according to the approved treatment and dosage) or intolerance (at Investigator's discretion and/or experience of intolerable AE or toxicity such as infusion related reaction, hypersensitivity, anaphylaxis or severe toxicity) to anti-TNF therapy (experience of severe AE or toxicity). 4. Current treatment for RA on an outpatient basis: - Receiving MTX 7.5 - 25mg/week (oral or parenteral) for at least 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 (<10 mg/week), 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. - Leflunomide must be withdrawn at least 12 weeks prior to Day 1 or a minimum of 4 weeks prior to Day 1 if after 11 days of standard cholestyramine washout. - All DMARDs different from MTX and leflunomide must be withdrawn at least 4 ~ 8 weeks prior to Day 1. - If receiving current treatment with oral corticosteroids, the dose must not exceed 10 mg/day prednisone or equivalent. During the 4 weeks prior to Day 1 the dose must be stable. - The most recent IM/intra-articular steroid injection should be ?6 weeks prior to Day 1. - If receiving current treatment with NSAIDs at the time of Screening, the patient must remain on a stable dose for at least 3 weeks prior to Day 1. - Patients are willing to receive oral folic or folinic acid or equivalent during the entire study (mandatory co-medication for MTX treatment), according to local standards and availability. 5. Men and women of childbearing potential must use highly effective methods of contraception during the course of the treatment period and for at least 12 months after the last infusion of study drug. A man or women is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active. Examples of highly effective contraception include: - combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation 1: * oral * intravaginal * transdermal - progestogen-only hormonal contraception associated with inhibition of ovulation 1: * oral * injectable * implantable - intrauterine device (IUD) - intrauterine hormone-releasing system (IUS) - bilateral tubal occlusion - vasectomised partner - sexual abstinence The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. 6. 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 no
Exclusion criteria
Exclusion criteria: Parts A and B: 1 Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 12 months after the last infusion of study drug. 2 Class IV as per the Classification of Global Functional Status in Rheumatoid Arthritis (as per ACR 1991 Revised Criteria) or wheelchair/bed-bound. 3 History of or current inflammatory joint disease other than RA 4 History of or current systemic autoimmune disorder with the exception of the secondary Sjögren's syndrome. 5 Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening. Part C only: 1. Females who are pregnant, breastfeeding, or planning a pregnancy during the Treatment Period of and 12 months after the last infusion of study drug. 2. Patients with IgG levels at Week 36 <300 mg/dL. IgG may be repeated one time to establish eligibility upto 4 weeks prior to the 1st infusion of the 3rd course. 3. Patients with ANC at Week 36 <1,500 cells/µL. ANC may be repeated one time to establish eligibility upto 4 weeks prior to the 1st infusion of the 3rd course. 4. Any significant cardiac disease. 5. Patients who, based on the Investigator's judgment, have a clinically significant or unstable medical or surgical condition that may preclude safe and complete study participation. Conditions may also include cardiovascular, vascular, pulmonary, hepatic, renal, endocrine or neurological conditions as determined by medical history, physical examination, or laboratory tests or electrocardiogram (ECG). 6. Patients who, in the judgment of the Investigator, are likely to be non-compliant or uncooperative during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to compare the pharmacokinetics (PK) of SAIT101 (proposed rituximab biosimilar) versus rituximab licensed in the European Union (MabThera®, brand name in EU) versus rituximab licensed in the United States (Rituxan®, brand name in US) in patients with RA.;Secondary Objective: 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 in patients with rheumatoid arthritis (RA). With the extension phase of the study, the descriptive evaluation of the long-term safety and immunogenicity of SAIT101 is also included.;Primary end point(s): Pharmacokinetics 1. Area under the concentration-time curve from time 0 (immediately predose on Day 1) to last quantifiable concentration 2. AUC from time 0 to infinity 3. AUC from time 0 to Day 15 prior to infusion 4. Maximum concentration (Cmax) after Day 15 infusion 5. Trough concentration (Ctrough) before the second infusion on Day 15 ;Timepoint(s) of evaluation of this end point: Pharmacokinetics: Baseline Day 1 (time 0), 3, 8, 15, 17, 29, 57, 85, 113, 141 (Part A) and Day 169 (Part B), as applicable | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Pharmacokinetics: Baseline Day 1 (time 0), 3, 8, 15, 17, 29, 57, 85, 113, 141 (Part A) and Day 169 (Part B), as applicable Pharmacodynamics: Baseline Day 1 (time 0), 3, 8, 15, 17, 29, 57, 85, 113, 141 (Part A) and Day 169, 253, 365 (Part B), as applicable Efficacy: Efficacy: Baseline, Week 24 // Baseline, Weeks 8, 16, 36, and 52 Immunogenicity: Day 1 predose and at Week 1, 2, 4, 12, 16, 24, 36, and 52, 54, 64, 76, 78, 88, and 100 Safety: continuously ;Secondary end point(s): Pharmacokinetics 1.AUC from Week 2 to Week 24 2. AUC from time 0 (immediately predose on Day 1) to Week 12 3. Time of maximum concentration (Tmax) post infusion on Day 15 4. Systemic clearance (CL) 5. Volume of distribution (VD) 6. Terminal half-life (t½) Pharmacodynamics 1. Depletion of CD19+ B cell count at Week 24 2. Time needed to B cell depletion 3. Duration of CD19+ B cell depletion 4. % CD19+ B-cell count vs. baseline at Week 24 5. AUC of CD19+ B-cell count change at Week 24 6. Change from Baseline in CD19+ B cell count during the study period 7. Change from Baseline in IgG, IgM, and IgA levels at Weeks 24 and 52 8. Change from Baseline in CRP levels at Weeks 8, 16, 24, 36, and 52 Efficacy: 1. Change in DAS28 score 2. ACR20 response rates 3. ACR50 response rates and ACR70 response rates 4. Individual components of the ACR improvement criteria 5. Change in DAS28-CRP 6. Major clinical response (continuous ACR70 for at least 24 weeks) 7. Clinical remission (defined by SDAI < 3.3) 8. Proportion of patients with European League Against Rheumatism (EULAR) response Immunogenicity 1. Incidence of HACA and neutralizing antibody Safety SAEs, AEs, ADRs, Vital signs, Clinical laboratory parameters including hematology, chemistry and urinalysis, Physical findings, Concomitant medication, incidence of rescue medication, where rescue medication is defined as the use of non-biologic DMA | — |
Countries
Bosnia and Herzegovina, Bulgaria, Czech Republic, Germany, Hungary, India, Italy, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, United States
Contacts
Public ContactQuintiles Call Center
Quintiles Ltd
Outcome results
None listed