Evaluation of different oral doses and regimens of GLPG0634 given for 24 weeks in patients with active rheumatoid arthritis and an insufficient response to methotrexate alone
- Conditions
- moderately to severely active rheumatoid arthritisMedDRA version: 14.1Level: PTClassification code 10039073Term: Rheumatoid arthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2012-003635-31-ES
- Lead Sponsor
- Galapagos NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 595
To be eligible for study entry subjects must fulfil all of the following
criteria:
1. Male or female subjects who are >=18 years of age, on the day of signing informed consent.
2. Diagnosis of RA since at least 6 months prior to Screening and
meeting the 2010 ACR/EULAR criteria of RA and ACR functional class IIII.
3. Have >=6 swollen joints (from a 66 joint count) and >=8 tender joints (from a 68 joint count) at Screening and Baseline, and a Screening serum CRP >=1.2 x ULN.
4. Have received MTX (oral or parenteral) for >=6 months and have been on a stable dose (15 mg/week to 25 mg/week) of MTX for at least 4 weeks prior to Screening and willing to continue on this regimen for the duration of the study. Stable doses of MTX as low as 10 mg/week are allowed, when there is documented evidence of intolerance or safety issues at higher doses.
5. If taking oral steroids, these should be at a dose <=10 mg/day of prednisone or prednisone equivalent and stable for at least 4 weeks prior to Screening.
6. If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least 2 weeks prior to Screening.
7. The results of the following laboratory tests performed at the central laboratory at Screening must be within the limits specified below:
a) Hemoglobin >=10 g/dL (International System of Units [SI]: >=100 g/L);
b) WBCs >=3.0 x 103 cells/mm3 (SI: >=3.0 x 109 cells/L);
c) Neutrophils >=2.0 x 103 cells/mm3 (SI: >=2.0 x 109 cells/L);
d) Lymphocytes >=1.0 x 103 cells/mm3 (SI: >=1.0 x 109 cells/L);
e) Platelets >=100 x 103 cells/mm3 (SI: >=100 x 109 cells/L);
f) Serum ALT and aspartate aminotransferase (AST) <=1.5 x ULN;
g) Total bilirubin level <=1.25 x ULN;
h) Alkaline phosphatase <=1.5ULN;
i) Lipase <=1.5 x ULN and amylase <=1.5ULN;
j) Creatinine clearance >60 mL/min and blood urea nitrogen (BUN)
within normal ranges. Creatinine clearance will be calculated using the Cockroft-Gault formula.
8. Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year (12 consecutive months without menses); in case of doubt a determination of serum FSH can be done with FSH levels above 35 mIU/mL being confirmative for menopause.
9. Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 12 weeks after the last dose of study medication. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed more than one year before Screening), or double barrier contraception.
10. Sexually active men must agree to use a medically acceptable form of contraception (double barrier) during the study and continue its use for at least 12 weeks after the last dose of study medication.
11. Able and willing to sign the informed consent as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to Screening evaluations and agree to schedule of assessments.
12. Judged to be in good health, except for their RA, as deter ined by the investigator based upon the results of medical history, laboratory profile,
physical examination, chest X-ray, and a 12-lead ECG performed during Screening.
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 475
F.1.3 Elderly (>=
1. Current therapy with any DMARD other than MTX, including oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or D penicillamine within 4 weeks prior to Baseline, cyclosporine within 8 weeks prior to Baseline, and leflunomide within 3 months prior to Baseline or a minimum 4 weeks prior to Baseline if after 11 days of standard cholestyramine therapy.
2. Current or previous RA treatment with a biologic DMARD, with the exception of biologic DMARDs
-administered in a single clinical study setting, and;
-more than 6 months prior to Screening (12 months for rituximab or other B cell depleting agents), and;
-where the biologic DMARD was effective, and if discontinued, this should not be due to lack of efficacy.
3. Previous treatment at any time with a cytotoxic agent, other than MTX, before Screening. These agents include, but are not limited to chlorambucil, cyclophosphamide, nitrogen mustard, or other alkylating agents.
4. Previous use of JAK or SYK inhibitors.
5. Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to Screening.
6. Known hypersensitivity to study medication ingredients or a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.
7.Positive serology for human HIV 1 or 2 or hepatitis B or C or any
history of hepatitis from any cause with the exception of hepatitis A.
8.Immunocompromised subjects who in the opinion of the investigator
are at an unacceptable risk for participating in the study.
9.Previous history of symptomatic herpes zoster or herpes simplex
infection within 12 weeks prior to Screening or have a history of
disseminated/complicated herpes zoster infection (multi-dermatomal
involvement, ophthalmic zoster CNS involvement or postherpetic
neuralgia).
10.Known active infection of any kind (excluding fungal infection of nail
beds-, or any major episode of infection requiring hospitalization or
treatment with parenteral (intramuscular or IV) anti-infectives
(antibiotics, antiviral, anti-fungals or anti-parasitic agents) within 4
weeks of the Screening Visit or completion of oral anti infectives within 2
weeks of the Screening Visit.
11.Currently on any therapy for chronic infection (such as pneumocystis,
CMV, herpes simplex, herpes zoster and atypical mycobacteria).
12.History of any inflammatory rheumatological disorder other than RA
except secondary Sjögren´s Syndrome.
13.Any surgical procedure, including bone/joint surgery/synovectomy
(including joint fusion or replacement) within 24 weeks prior to the
Screening Visit.
14.History of moderate to severe congestive heart failure (New York
Heart Association [NYHA] class III or IV), recent (within 24 hours prior
to study entry) cerebrovascular accident and any other condition which,
in the opinion of the investigator, would put the subject at risk by
participation in the study.
15.History or current symptoms of GI tract ulceration and/or
diverticulitis.
16.History of malignancy within the past 5 years (except for basal cell
carcinoma of the skin or cervical carcinoma in situ that has been treated
with no evidence of recurrence).
17.History of lymphoproliferative disease; or signs and symptoms
suggestive of possible lymphoproliferative disease including
lymphadenopathy or splenomegaly.
18.History of active or latent tuberculosis (TB) infection as determined
by either:
a)positive QuantiFERON TB Gold test result OR
b)chest radiograph (both posterio
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