A Randomized, Parallel, Double-Blind, Placebo-Controlled Dose Regimen Finding Study to Evaluate the Safety and Efficacy of TRU-015 in Subjects With Active Seropositive Rheumatoid Arthritis on a Stable Background of Methotrexate
- Conditions
- Rheumatoid ArthritisMedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2007-006150-25-AT
- Lead Sponsor
- Wyeth Research Division of Wyeth Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 216
1. Age = 18 years at time of signing the ICF
2.Meets the American Rheumatism Association 1987 revised criteria for classification of RA.
3.ACR functional class I-III.
4.At screening, active RA consisting of = 5 swollen and = 5 tender joints (28-joint count: see Attachment 3) and one or both of the following CRP or ESR criteria:
a. Erythrocyte sedimentation rate (ESR)(Westergren) = 28 mm/hr
b. CRP = 15 mg /L
5.Must be seropositive: Defined as a documented history of one or both of the following RF or anti-CCP criteria. If a documented history of one or both of the following RF or anti-CCP criteria is not available, RF and anti-CCP will be tested with screening labs:
a. Positive RF
b.Positive anti-CCP
6.Currently receiving MTX regimen of 7.5 to 25mg of MTX weekly for at least 12 weeks prior to study day 1. The dose and route of administration of MTX must be stable for at least 4 weeks prior to study day 1.
7.Women of childbearing potential must have a negative urine pregnancy test at screening and baseline. Women of childbearing potential are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Women of non-childbearing potential are defined as either postmenopausal (history of amenorrhea for = 52 weeks) or who are surgically sterile, such as after hysterectomy, bilateral oophorectomy, or tubal ligation (procedure performed = 1 year before screening). This information must be documented in the subject’s source documents.
8.Women of childbearing potential must agree and commit to the use of hormonal contraception, double-barrier contraception, or an intrauterine device throughout the entire study (defined as the signing of the ICF to the completion of the Conclusion of Subject Participation). Double-barrier contraception is defined as the use of a diaphragm, condom, or cervical cap plus a spermicidal vaginal foam, cream, jelly, suppository, or sponge. WOCBP who have a vasectomized partner are also eligible for participation. Vasectomized partners must have had their vasectomy more than 6 months before study day 1.
9.Men must agree and commit to use a medically acceptable form of contraception for the entire study (defined as the signing of the ICF to the completion of the Conclusion of Subject Participation) unless surgically sterile. Medically acceptable forms of contraception include properly used barrier forms of contraception.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
;
1. Age = 18 years at time of signing the ICF
2.Meets the American Rheumatism Association 1987 revised criteria for classification of RA.
3.ACR functional class I-III.
4.At screening, active RA consisting of = 5 swollen and = 5 tender joints (28-joint count: see Attachment 3) and one or both of the following CRP or ESR criteria:
a. Erythrocyte sedimentation rate (ESR)(Westergren) = 28 mm/hr
b. CRP = 15 mg /L
5.Must be seropositive: Defined as a documented history of one or both of the following RF or anti-CCP criteria. If a documented history of one or both of the following RF or anti-CCP criteria is not available, RF and anti-CCP will be tested with screening labs:
a. Positive RF
b.Positive anti-CCP
6.Currently receiving MTX regimen of 7.5 to 25mg of MTX weekly for at least 12 weeks prior to study day 1. The dose and route of administration of MTX must be stable for at least 4 weeks prior to study day 1.
7.Women of childbearing potential must have a negative urine pregnancy test at screening and baseline. Women of childbearing potential are defined as women who are biologically capable of becoming pregnant, including women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Women of non-childbearing potential are defined as either postmenopausal (history of amenorrhea for = 52 weeks) or who are surgically sterile, such as after hysterectomy, bilateral oophorectomy, or tubal ligation (procedure performed = 1 year before screening). This information must be documented in the subject’s source documents.
8.Women of childbearing potential must agree and commit to the use of hormonal contraception, double-barrier contraception, or an intrauterine device throughout the entire study (defined as the signing of the ICF to the completion of the Conclusion of Subject Participation). Double-barrier contraception is defined as the use of a diaphragm, condom, or cervical cap plus a spermicidal vaginal foam, cream, jelly, suppository, or sponge. WOCBP who have a vasectomized partner are also eligible for participation. Vasectomized partners must have had their vasectomy more than 6 months before study day 1.
9.Men must agree and commit to use a medically acceptable form of contraception for the entire study (defined as the signing of the ICF to the completion of the Conclusion of Subject Participation) unless surgically sterile. Medically acceptable forms of contraception include properly used barrier forms of contraception.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1.Pregnant women, nursing mothers, or women planning to become pregnant during the study.
2.Any cardiovascular, neurological, metabolic, immunological, infectious, hepatic, or renal condition that, in the opinion of the investigator, could be detrimental to subjects participating in this study, including any clinically important deviations from normal clinical laboratory values or important concurrent medical events.
3.Any active, severe infections
4.Severe heart failure (NYHA Class IV) or severe, uncontrolled cardiac disease
5.Subjects with active tuberculosis as per country specific guidelines or history of tuberculosis.
6.Subjects with other objectively confirmed or suspected rheumatic diseases including, but not limited to, Lyme disease, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious arthritis, reactive arthritis or overlap syndrome.
7.Cancer, or a history of cancer (other than adequately resected cutaneous basal cell and squamous cell carcinomas or in situ cervical cancer).
8.History of alcohol or drug abuse that, in the opinion of the investigator, would interfere with the ability to comply with the study protocol.
9.Documented immunodeficiency disease, including subjects with known human immunodeficiency virus (HIV) at the time of screening.
10Subjects positive for hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb), or hepatitis C antibody (HepCAb) with confirmation by RIBA, or history of drug-induced liver injury, or documented liver cirrhosis or documented fibrosis at any time before the Baseline visit.
11.Any clinically significant laboratory abnormality, including: Hemoglobin < 8.5 g/dL (SI units: < 85 g/L); White blood cell (WBC) count < 3.50 x 103/mm3 (SI units: < 3.50 x 109/L); Platelets < 125,000/mm3 or = 1,000,000/mm3 (SI units: < 125 x 109/L or = 1,000 x 109/L); Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) > 1.5 x upper limit of normal (ULN); Serum creatinine > 2 mg/dL (SI units: >177 µmol/L)
12.Clinically significant finding on chest radiograph. Chest x-ray must be performed during screening period, unless a radiograph was performed within the 24 weeks prior to Baseline.
13.For subjects who consent to the MRI sub-study:a.Any permanent reactive metal implants contained in or on the body.b.Contraindications to Gadolinium contrast agents including, but not limited to, glomerular filtration rate (GFR) < 30 ml/min.
14.Lack of peripheral venous access.
15.Any prior use of rituximab, or other B cell depleting agents.
16.Receipt of live vaccine = 8 weeks prior to the screening visit.
17.Known hypersensitivity to mouse immunoglobulin, mouse/human chimeric immunoglobulin, or other biopharmaceutical proteins.
18.Contraindications for treatment with MTX.
19.Known/documented hypersensitivity to corticosteroids, acetaminophen/paracetamol, or antihistamine that will be used prior to administration of the IV TA (TRU-015 or placebo).
20.Within 24 weeks before baseline; received cyclophosphamide, chlorambucil, IV immunoglobulin (IG), Prosorba column (extracorporeal immunoadsorption protein A column), or leflunomide
21.Within 12 weeks before baseline: received hydroxychloroquine, any investigational drug or procedure
22.Within 8 weeks before baseline, received abatacept, adalimumab, or infliximab
23. Within 4 weeks before baseline:
a.Received any other Disease-Modifying Antirheumatic Drug;
1.Pregnant women, nursing mothers, or women planning to become pregnant during the study.
2.Any cardiovascular, neurological, metabolic, immunological, infectious, hepatic, or renal condition that, in the opinion of the investigator, could be detrimental to subjects participating in this study, including any clinically important deviations from normal clinical laboratory values or important concurrent medical events.
3.Any active, severe infections
4.Severe heart failure (NYHA Class IV) or severe, uncontrolled cardiac disease
5.Subjects with active tuberculosis as per country specific guidelines or history of tuberculosis.
6.Subjects with other objectively confirmed or suspected rheumatic diseases including, but not limited to, Lyme disease, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, systemic vasculitis, polymyositis, infectious arthritis, reactive arthritis or overlap syndrome.
7.Cancer, or a history of cancer (other than adequately resected cutaneous basal cell and squamous cell carcinomas or in situ cervical cancer).
8.History of alcohol or drug abuse that, in the opinion of the investigator, would interfere with the ability to comply with the study protocol.
9.Documented immunodeficiency disease, including subjects with known human immunodeficiency virus (HIV) at the time of screening.
10Subjects positive for hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb), or hepatitis C antibody (HepCAb) with confirmation by RIBA, or history of drug-induced liver injury, or documented liver cirrhosis or documented fibrosis at any time before the Baseline visit.
11.Any clinically significant laboratory abnormality, including: Hemoglobin < 8.5 g/dL (SI units: < 85 g/L); White blood cell (WBC) count < 3.50 x 103/mm3 (SI units: < 3.50 x 109/L); Platelets < 125,000/mm3 or = 1,000,000/mm3 (SI units: < 125 x 109/L or = 1,000 x 109/L); Aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) > 1.5 x upper limit of normal (ULN); Serum creatinine > 2 mg/dL (SI units: >177 µmol/L)
12.Clinically significant finding on chest radiograph. Chest x-ray must be performed during screening period, unless a radiograph was performed within the 24 weeks prior to Baseline.
13.For subjects who consent to the MRI sub-study:a.Any permanent reactive metal implants contained in or on the body.b.Contraindications to Gadolinium contrast agents including, but not limited to, glomerular filtration rate (GFR) < 30 ml/min.
14.Lack of peripheral venous access.
15.Any prior use of rituximab, or other B cell depleting agents.
16.Receipt of live vaccine = 8 weeks prior to the screening visit.
17.Known hypersensitivity to mouse immunoglobulin, mouse/human chimeric immunoglobulin, or other biopharmaceutical proteins.
18.Contraindications for treatment with MTX.
19.Known/documented hypersensitivity to corticosteroids, acetaminophen/paracetamol, or antihistamine that will be used prior to administration of the IV TA (TRU-015 or placebo).
20.Within 24 weeks before baseline; received cyclophosphamide, chlorambucil, IV immunoglobulin (IG), Prosorba column (extracorporeal immunoadsorption protein A column), or leflunomide
21.Within 12 weeks before baseline: received hydroxychloroquine, any investigational drug or procedure
22.Within 8 weeks before baseline, received abatacept, adalimumab, or infliximab
23. Within 4 weeks before baseline:
a.Received any other Disease-Modifying Antirheumatic Drug
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method