A study comparing SAIT101 to MabThera® in Subjects with Severe Rheumatoid Arthritis (RA)

• Register: EUCTR
• Last refreshed on: 21 August 2012
• Main ID: EUCTR2011-004171-36-CZ
• Date of registration: 30/11/2011
• Prospective Registration: Yes
• Primary sponsor: Samsung Electronics Co. Ltd.
• Public title: A study comparing SAIT101 to MabThera® in Subjects with Severe Rheumatoid Arthritis (RA)
• Scientific title: A Randomized, Double-blind, Parallel Group, Multicenter Trial to Compare the Efficacy, Safety, Pharmacodynamics and Pharmacokinetics of SAIT101 to MabThera® in Subjects with Severe Rheumatoid Arthritis (RA)
• Date of first enrolment: 15/02/2012
• Target sample size: 616
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004171-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Brazil, Canada, Czech Republic, Hungary, Korea, Republic of, Mexico, Poland, Romania, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Turkey, United Kingdom

Contacts

• Name: Quintiles Contact Centre
• Affiliation: Quintiles Limited

• Name: Quintiles Contact Centre
• Affiliation: Quintiles Limited

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability and willingness to provide written informed consent, prior to any study specific procedures, and to comply with the requirements of the protocol.
2. Male or female outpatient, at least 18 years of age at Screening.
3. Severe active RA defined as:
(a) Diagnosis of RA according to the revised (1987) ACR criteria for the classification of RA for at least 3 months prior to study entry (see Appendix 3).
(b) Radiological confirmation of bone erosion (X-ray. Existing evidence [X-ray not more than 1 year old] also accepted).
(c) = 6 swollen joints and = 6 tender/painful joints (from the 66/68 joint count system).
(d) hsCRP = 1.0 mg/dL and/or an ESR = 28 mm/hour at Screening.
(e) Positive RF (= 20 units/mL) and/or anti CCP antibodies (= 10 units/mL) at Screening.
4. Currently receiving, or have previously received, DMARDs, including one or more TNF inhibitor therapies, for the treatment of RA at a label approved dose for at least 3 months, and have had an inadequate or intolerable response to at least one of those administrations. NB: All biologic DMARDs and IL-1 and IL-6 inhibitors are subject to a washout period prior to randomization (see Table 7).
5. Current treatment for RA on an outpatient basis:
(a) Receiving MTX 10-25 mg/week (oral or parenteral) for at least 3 months, including the last 1 month prior to randomization at a stable dose, via the same route of administration and formulation. Subjects receiving a lower dose of MTX (< 10 mg/week), stable for 1 month prior to randomization, should be doing so as a result of a documented evidence of intolerance to higher doses of MTX.
(b) Subjects may be taking oral hydroxychloroquine provided that the dose is not greater than 400 mg/day and has been stable for a minimum of 3 months prior to Day 1. The hydroxychloroquine treatment will need to be continued at a stable dose with the same formulation until the end of the study.
(c) Leflunomide must be withdrawn at least 3 months prior to the beginning of the treatment period or a minimum of 1 month prior to the beginning of the treatment period if after 11 days of standard cholestyramine washout.
(d) All DMARDs different from MTX, hydroxycholoquine and leflunomide must be withdrawn at least 1 month prior to the beginning of the treatment period.
(e) If receiving current treatment with oral corticosteroids, the dose must not exceed 10 mg/day prednisolone or equivalent. During the 1 month prior to Day 1 the dose must be stable (see Section 5.1.3).
(f) The most recent steroid injection should be =6 weeks prior to Day 1.
(g) If receiving current treatment with NSAIDs at the time of Screening, the subject must remain on a stable dose for at least 3 weeks prior to Day 1.
(h) Subjects are willing to receive oral folic acid (at least 5 mg/week) or equivalent during the entire study (mandatory co-medication for MTX treatment).
6. For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, intrauterine device, physical barrier) during the course of the treatment period and for at least 12 months after the last dose of investigational product.
7. Female subjects 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.
8. Female subjects must not be actively breast-feeding throughout the entire study period and until 12 months after th
Exclusion criteria:
1. Females who are pregnant, nursing, or planning a pregnancy during the period of the study.
2. American College of Rheumatology functional Class IV or wheelchair/bed bound.
3. Have any significant systemic involvement with RA such as vasculitis, pulmonary fibrosis or Felty’s syndrome.
4. History of or current inflammatory joint disease other than RA (including but not limited to gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy or Lyme disease) or other systemic autoimmune disorder, with the exception of the secondary Sjögren's syndrome, (including but not limited to systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease or other overlap syndrome).
5. History of infected prosthetic joint.
6. Positive serological test for HBsAg and HBcAb or for hepatitis C serology.
7. History of HIV infection.
8. History of active/latent TB, as determined by TB test.
9. Subjects with acute clinical manifestations of herpes zoster virus.
10. Subjects with history of severe herpes zoster defined by involvement of more than one dermatome, ophthalmic involvement and/or requiring hospital admission within 5 years prior to Baseline.
11. Active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization within 3 months prior to Baseline or requiring treatment with i.v. anti infective agents within 6 weeks prior to Baseline or oral anti-infective agents within 2 weeks prior to Baseline.
12. Any significant cardiac disease (e.g. coronary artery disease with unstable angina, coronary heart failure NYHA Class III and IV, familial long QT syndrome, uncontrolled cardiac disease).
13. History of moderate to severe COPD and/or history of severe COPD exacerbation(s) within the last 12 months.
14. Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
15. Administration of a live/attenuated vaccine in the 1 month prior to randomization.
16. History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the investigational product.
17. Hypogammaglobulinemia (IgG < 5.0 g/L and/or IgM < 0.20 g/L).
18. Subjects having undergone a splenectomy.
19. Subjects with hemoglobin < 8.5 g/dL, WBC count < 3000 cells/µL, ANC < 2000 cells/µL, lymphocyte count < 800 cells/µL or platelet count < 100,000 cells/µL at Screening. If a subject has findings marginally below this limit, re testing is allowed, at the investigator’s discretion, within the 30 day period between Visit 1 and 2.
20. AST, ALT, GGT or alkaline phosphatase levels > 1.5 times (for Part A) or > 3 times (for Part B) the ULN at Screening or serum creatinine > 2 times ULN. The AST and ALT may be repeated once within the Screening period if the initial result exceeds this limit, and the lesser value accepted if it meets this criterion.
21. Subjects with a history of solid-organ transplantation.
22. History of cancer within the last 5 years treated with anti-cancer chemotherapy, including solid tumors and hematologic malignancies and carcinoma in situ (except basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that have been excised and cured).
23. Subjects with a current or past history of alcohol or drug abuse.
24. A

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Severe Rheumatoid Arthritis (RA)
MedDRA version: 14.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: SAIT101
Product Code: SAIT101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Current Sponsor code: SAIT101
Other descriptive name: Chimeric human/mouse anti-CD-20 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: MabThera®
Product Name: MabThera®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: • AUC time curve from time 0 (immediately pre-dose at Day 1) to the time of the last quantifiable concentration (AUC0-t) at Week 24 and Cmax post infusion on Day 15.
• ACR20 response rate at Week 24.

Main Objective: The primary objective of the study is to compare the efficacy of SAIT101 to MabThera® in subjects with severe RA.

Primary end point(s): • The primary PK endpoints for Part A are the area under the concentration-time curve from time 0 (immediately pre-dose at Day 1) to the time of the last quantifiable concentration (AUC0-t) at Week 24 and the maximum concentration (Cmax) post infusion on Day 15.
• The primary efficacy variable for the whole study is the ACR20 response rate.

Secondary Objective: The secondary objectives of the study are to compare the pharmacodynamics (PD), safety, tolerability and immunogenicity of SAIT101 to MabThera® in subjects with severe RA.

Secondary Outcome(s)

Secondary end point(s): • ACR20 response rates.
• ACR50 response rate and ACR70 response rate.
• Individual components of the ACR improvement criteria:
o Swollen and tender joint count (the 66/68 joint count system)
o Subject’s assessment of pain (assessed on 1-100 mm Visual Analogue Scale [VAS])
o Physician’s global assessment of disease activity (assessed on 1-100 mm VAS)
o Subject’s assessment of disease activity (assessed on 1-100 mm VAS)
o Subject’s assessment of disability (Health Assessment Questionnaire Disability Index)
o C-reactive protein level
• Change in the DAS28.
• Major clinical response (continuous ACR70).
• Proportion of subjects with European League Against Rheumatism response (good response, moderate response or no structural joint damage).
• Assessment of structural joint damage.

Timepoint(s) of evaluation of this end point: • ACR20 response rates at Weeks 4, 8, 12, 16 and 52.
• ACR50 response rate and ACR70 response rate at Weeks 4, 8, 12, 16, 24 and 52.
• Individual components of the ACR improvement criteria at Day 1 and at Weeks 4, 8, 12, 16, 24 and 52:
• Change in the DAS28 from Baseline to Weeks 4, 8, 12, 16, 24 and 52.
• Major clinical response (continuous ACR70 for at least 24 weeks).
• Proportion of subjects with European League Against Rheumatism response at Weeks 4, 8, 12, 16, 24 and 52.
• Assessment of structural joint damage at Screening and Week 52.

Secondary ID(s)

S101-RGL-003

Source(s) of Monetary Support

Samsung Electronics Co. Ltd.