Rheumatoid arthritis MedDRA version: 14.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: GLPG0634
Pharmaceutical Form: Capsule, hard
Current Sponsor code: GLPG0634
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of
Sponsors
Galapagos SASU
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects who are 18 to 70 years of age, on the day of signing informed consent. 2. Fulfill the revised 1987 American Rheumatism Association (ARA) criteria (Appendix 1) for the classification of RA. 3. Have = 5 swollen joints (from a 66 joint count) and = 5 tender joints (from a 68 joint count), and a serum CRP =1.0 mg/dL. 4. Have received MTX for > 12 weeks and be on a stable dose (7.5 mg/week to 25 mg/week [extremes included]) of MTX for at least 4 weeks prior to screening and willing to continue on this regimen for the duration of the study. 5. If taking oral steroids, these should be at a dose =10 mg/day of prednisone or prednisone equivalent and stable for at least four weeks prior to screening. 6. If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least two 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 =8.5 g/dL (International System of Units [SI]: =85 g/L); b. White blood cells =3.0 x 103 cells/mm3 (SI: =3.0 x 109 cells/L); c. Neutrophils =1.5 x 103 cells/mm3 (SI: =1.5 x 109 cells/L); d. Platelets =100 x 103 cells/mm3 (SI: =100 x 109 cells/L); e. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =1.5 x upper limit of laboratory normal range (ULN); and f. Total bilirubin level =1.25 x ULN; g. Lipase and amylase within normal range. 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 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Current therapy with any disease modifying anti-rheumatic drug (DMARD) other than MTX, including oral or injectable gold, sulfasalazine, hydroxychloroquine, azathioprine, or D penicillamine within four weeks prior to screening, cyclosporine within eight weeks prior to screening, and leflunomide within three months prior to screening. 2. Current or previous RA treatment with a biological agent, with the exception of biologics administered in a single clinical study setting more than six months prior to screening (12 months for rituximab or other B cell depleting agents). 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 the study drug, GLPG0634. 5. Receipt of an intra-articular or parenteral corticosteroid injection within four weeks prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4.;Secondary Objective: • To evaluate the efficacy of GLPG0634 compared to placebo in terms of ACR response criteria at every visit (ACR20, ACR50, ACR70), time to ACR20 response, and DAS28 (CRP). • To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of AEs, laboratory test abnormalities, vital signs, and ECG. • To characterize the PK and PD of GLPG0634 and its metabolite (G254445) in targeted population. • To explore the potential interaction of GLPG0634 on MTX PK. ;Primary end point(s): The primary efficacy endpoint will be the number and percentage of subjects in each GLP0634 dose group and placebo group achieving an ACR20 response (ACR20 response rate) at Week 4.;Timepoint(s) of evaluation of this end point: at Week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints will include: • ACR20 response rate at Weeks 1, 2, and 4; • Time to ACR20 response; • Number and percentage of subjects achieving an ACR50 response (ACR50 response rate) at Weeks 1, 2, and 4; • Number and percentage of subjects achieving an ACR70 response (ACR70 response rate) at Weeks 1, 2, and 4; • Change and percentage change from baseline in DAS28(CRP) at Weeks 1, 2, and 4; and • Change and percentage change from baseline in the core components of the ACR response and DAS28(CRP) at Weeks 1, 2, and 4. The secondary safety endpoints will include: • Incidence and severity of AEs; • Vital signs (supine heart rate, blood pressure [systolic and diastolic], and oral temperature); • 12-lead ECG; and • Clinical laboratory tests (hematology, Inhibin B [in males only], serum chemistry, coagulation, and urinalysis). The secondary PK endpoints will include: • Plasma concentrations of GLPG0634 and its metabolite G254445 in all subjects at Weeks 1, 2 and 4, and EDV (if applicable); • For the subjects willing to participate to the PK sub-study, the following plasma PK parameters will be calculated for GLPG0634/G254445 as well as for MTX and 7 OH-MTX: o Maximum plasma concentration [Cmax] o Time corresponding to Cmax [tmax] o Area under the plasma drug concentration-time curve over 24h[AUC0-24h] o Metabolite over parent ratio [R] Additional PK assessments may be performed as appropriate. The secondary PD endpoints will include: • Quantification of proteins (cytokines, chemokines, and others) in plasma in all subjects at Day -1, Week 1, Week 2, and Week 4, and EDV (if applicable). • Modulation of plasmatic proteins linked to JAK-STAT signaling pathways, and/or disease-related will be evaluated.;Timepoint(s) of evaluation of this end point: Please refer to the protocol, section 12 for timepoints of evaluation of secondary endpoints. | — |
Countries
European Union, Hungary, Moldova, Republic of, Russian Federation, Ukraine
Contacts
Public ContactClinical Trial Information Desk
Galapagos NV
Outcome results
None listed