Rheumatoid Arthritis MedDRA version: 19.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870
Conditions
Interventions
Product Name: GP2013
Product Code: GP2013
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: GP2013
Concentration u
Sponsors
Hexal AG (a Sandoz company)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or non-pregnant, non-lactating female patients at least 18 years of age at screening, who give written informed consent before any assessment is performed. 2. Patients must have the diagnosis of RA (according to American College of Rheumatology 2010 criteria). 3. Patients must have received at least one full treatment course of rituximab for the therapy of RA (i.e. 2 complete i. v. infusions of 1000 mg of Rituxan® in the USA or MabThera® in the EU) six to eighteen months prior to randomization. 4. Patients must be eligible for the subsequent treatment course with Rituxan® or MabThera® according to the clinical judgment of the Investigator. 5. Patients must be on a stable dose of methotrexate (MTX) (7.5 to 25 mg per week) for at least 4 weeks prior to randomization. If patients receive a combination of DMARDs (MTX + hydroxychloroquine or MTX+ chloroquine or MTX+ sulfasalazine) these DMARDs must be also on a stable dose for at least 4 weeks prior to randomization. 6. Patients must be on a stable dose of folic acid or folinic acid (= 5 mg per week) for at least 4 weeks prior to randomization. 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 80 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. RA of functional status class IV classified according to the ACR 1991 revised criteria. 2. Systemic manifestation of RA, with the exception of Sjögren’s syndrome. 3. Use of any other investigational drugs within 30 days prior to screening (or within 5 half-lives or until the expected PD effect has returned to baseline, whichever is longer). 4. Requiring treatment with any biological medicinal product during the study other than the study medication. 5. Treatment with any biologics for any indication since the start of last treatment with either Rituxan®/MabThera®. 6. History of severe hypersensitivity to either Rituxan®/MabThera® or any of its excipients, requiring drug discontinuation. 7. Any contraindication to Rituxan®/MabThera® or MTX. 8. Therapy with any DMARDs (including tofacitinib) other than MTX or combination of MTX with hydroxychloroquine or MTX with chloroquine or MTX with sulfasalazine within 4 weeks prior to randomization. In case of leflunomide it has to be discontinued 8 weeks prior to randomization (if a cholestyramine washout is performed, leflunomide has to be discontinued 4 weeks prior to randomization). 9. Previous treatment with any cell depleting therapies, including investigational agents. 10. Current treatment or need for treatment with any prohibited medications. 11. Any serious illness or uncontrolled medical condition, including but not limited to severe infections, significant hepatic or renal disease, uncontrolled hypertension (defined as =160/95), congestive heart failure (NYHA class III or IV), or other severe, uncontrolled cardiac disease. 12. Any medical condition which, in the investigator’s opinion, would preclude the patient from completing all protocol requirements. 13. Any of the following laboratory values at screening: WBC 3 × ULN (upper limit of normal); alanine aminotransferase (ALT) > 3 × ULN; gamma-glutamyl transferase (GGT) > 3 × ULN; alkaline phosphatase (AP) > 3 × ULN; glomerular filtration rate (GFR) < 60 mL/min/1.73m2 (GFR calculated as per 4-variable MDRD formula); immunoglobulin G (IgG) and/or IgM and/or IgA below LLN. 14. Positive serology to hepatitis C infection. 15. Positive serology to hepatitis B infection. 15a. In case a patient is HBsAg negative but positive for hepatitis B core antibody [anti-HBc], this patient can only be included after consultation with a hepatitis expert to clarify the potential risk of Hepatitis B reactivation, required Hepatitis B monitoring and antiviral therapy. 16. History of serious recurrent or chronic infectious disease (excluding fungal infections of the nail beds) or active systemic infection within 2 weeks prior to screening or during the screening period, except for common cold. 17. Severely immunocompromised state, including but not limited to Felty’s syndrome and known (HIV) infection. 18. Any malignancy prior to screening, with exception of adequately treated in situ carcinoma of the cervix uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer, or non-invasive malign colon polyps that have been removed with no evidence of recurrence. 19. Active tuberculosis. If a QuantiFERON®- Tuberculosis (TB) Gold test at screening is positive, further work-up, according to local guidelines/practices needs to be performed to conclusively establish that that the patient has no evidence of active tuberculosis. 20. Pregnan
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study objective is to identify potential safety risk of the transition from the originator product (US-licensed Rituxan® or EU-approved MabThera®) to GP2013 (proposed biosimilar product) as compared to continuous treatment with the originator product in terms of general safety and immunogenicity. ;Secondary Objective: Is no secondary objectives;Primary end point(s): The following safety variables will be evaluated: • Hypersensitivity reactions • Anaphylactic reactions • Infusion-related reactions • Immunogenicity (development of anti-drug-antibodies (ADA)) • Adverse events and serious adverse events • Other safety variables (vital signs, laboratory variables, body weight);Timepoint(s) of evaluation of this end point: All safety parameters will be analyzed on the safety analysis set (SAF). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Is no secondary endpoints;Timepoint(s) of evaluation of this end point: Is no secondary endpoints | — |
Countries
Germany, Hungary, Poland, United States
Contacts
Public ContactDmitrij Kollins
Hexal AG (a Sandoz company)
Outcome results
None listed