Rheumatoid arthritis MedDRA version: 20.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: ABP 798
Product Code: ABP 798
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
CAS Number: 1446410-99-6
Current Sponsor code: ABP 798
Other descr
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Men or women = 18 and = 80 years old 2.Subjects must be diagnosed with RA as determined by meeting 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA 3.Duration of RA of at least 6 months 4.Active RA defined as = 6 swollen joints and = 6 tender joints (based on 66/68 joint count excluding distal interphalangeal joints) at screening and baseline and at least one of the following at screening: •erythrocyte sedimentation rate (ESR) = 28 mm/hr •serum C-reactive protein (CRP) > 1.0 mg/dL 5.Subjects have had an inadequate response or intolerance to other DMARDs (which must include intolerance or inadequate response to one or more TNF inhibitor therapies). 6.Subjects must be taking methotrexate (MTX) for = 12 consecutive weeks and be on a stable dose of MTX 7.5 to 25 mg/week for = 8 weeks prior to receiving the investigational product (IP), and be willing to remain on a stable dose throughout the study 7.Subject has no known history of active tuberculosis 8.Subject has a negative test for tuberculosis during screening defined as either: •negative purified protein derivative (PPD) 4 weeks therapy, the subject must be deemed able and willing to complete the entire prophylaxis regimen in accordance with local guidance. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 270 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1.History of prosthetic or native joint infection 2.Active infection or history of infections as follows: •any active infection for which systemic anti-infectives were used within 4 weeks prior to first dose of IP •a serious infection, defined as requiring hospitalization or IV anti infectives within 8 weeks prior to the first dose of IP •recurrent or chronic infections or other active infection that, in the opinion of the Investigator, might cause this study to be detrimental to the subject 3.Known history of human immunodeficiency virus 4.Hepatitis B surface antigen (HbsAg), Hepatitis B core antibody (anti-HBc)positivity at screening (unless documentation of hepatitis B virus immunization), or Hepatitis C virus (HCV) antibody positivity at screening 5.Uncontrolled, clinically significant systemic disease such as diabetes mellitus, cardiovascular disease including severe heart failure (New York Heart Association [NYHA] class IV), or severe uncontrolled cardiac disease, renal disease, or liver disease 6.Malignancy within 5 years EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma 7.History of neurologic symptoms suggestive of central nervous system demyelinating disease 8.Laboratory abnormalities at screening, including any of the following: •hemoglobin < 9 g/dL •platelet count < 100,000/mm3 •white blood cell count < 3,000 cells/mm3 •aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 2.0 x the upper limit of normal •creatinine clearance < 50 mL/min (Cockroft-Gault formula) 9.Use of commercially available or investigational biologic therapies for RA as follows: •anakinra, etanercept within 1 month prior to first dose of IP •infliximab, abatacept, tocilizumab, golimumab, certolizumab, adalimumab within 3 months prior to first dose of investigational product •other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) prior to first dose of investigational product 10.Live vaccines within 28 days prior to the first dose of investigational product 11.Previous receipt of rituximab or a biosimilar of rituximab, or ocrelizumab 12.For women: pregnant or breast feeding, or planning to become pregnant while enrolled in the study and for 12 months after the last dose of investigational product 13.Sexually active subjects and their partners who are of childbearing potential (ie, neither surgically sterile nor postmenopausal) and not agreeing to use adequate contraception (eg, true abstinence, sterilization, birth control pills, Depo-Provera injections, or contraceptive implants) while on study and for 12 months after the last dose of investigational product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for this study is to demonstrate pharmacokinetic (PK) similarity of ABP 798 following 2 intravenous (IV) infusions of 1000 mg each, relative to that of 2 IV infusions of 1000 mg each of rituximab (US) and of rituximab (EU).;Secondary Objective: The secondary objectives are •to assess the clinical efficacy of ABP 798 compared with rituximab •to assess the safety and immunogenicity of ABP 798 compared with rituximab.;Primary end point(s): The primary PK endpoints will be AUCinf and Cmax ;Timepoint(s) of evaluation of this end point: The primary PK endpoints will be AUCinf and Cmax following the second infusion of the first dose. Additional PK endpoints will include AUC from time 0 on day 1 prior to the first infusion of the first dose to day 14 (AUC0 14 day), AUC from time 0 on day 1 prior to the first infusion of the first dose to week 12 (AUC0-12 wk), and Cmax following the first infusion of the first dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The efficacy endpoints are risk ratio (RR) of ACR20 (20% improvement in ACR core set measurements) and ACR50 (at least 50% improvement compared to baseline) and ACR70 (at least 70% improvement compared to baseline). PD endpoints will include the percent of subjects with complete depletion in CD19+ cell count. Disease Activity Score (DAS)28-CRP and Safety endpoints.;Timepoint(s) of evaluation of this end point: The efficacy endpoints are risk ratio (RR) of ACR20 at week 24 and Disease Activity Score (DAS)28 CRP change from baseline at week 24. These endpoints will also be assessed at weeks 8, 12, 40, and 48. In addition, ACR50 and ACR70 will also be assessed at weeks 8, 12, 24, 40, and 48. PD endpoints will be assessed from days 1 to 3. Safety endpoints include the following: •treatment-emergent AEs and serious adverse events (SAEs) •clinically significant changes in laboratory values and vital signs •incidence of antidrug antibodies | — |
Countries
Bulgaria, Canada, Estonia, Germany, Hungary, Poland, United States
Contacts
Public ContactIHQ Medical Info-Clinical Trials
Amgen (Europe) GmbH
Outcome results
None listed