Rheumatoid Arthritis MedDRA version: 16.1 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870
Conditions
Interventions
Product Code: QAL964
Pharmaceutical Form: Capsule
Current Sponsor code: QAL964
Other descriptive name: QAL964
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 10-25
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for inclusion in this study have to fulfill all of the following criteria. 1. Patient must be able to understand and communicate with the Investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study assessment is performed. 2. Male or non-pregnant, non-lactating female patients at least 18 years of age. 3. Presence of RA classified by ACR 2010 revised criteria for at least 3 months before screening. 4. At Baseline: Disease activity criteria defined by = 6 tender joints out of 28 and = 6 swollen joints out of 28 with: a. At least 1 of the following at screening: 1. Anti-CCP antibodies positive or 2. Rheumatoid Factor positive b. AND hsCRP = 8 mg/L. 5. Patients must be taking MTX for at least 3 months before randomization and have to be on a stable dose of at least 10 mg/week for at least 6 weeks before randomization. 6. Patients must be taking folic acid (or equivalent, e.g., folinic acid) supplementation before randomization. 7. Patients who were taking other DMARDs (in combination with MTX) will be allowed entry into study after appropriate washout period (except for MTX) prior to baseline of 28 days, except for leflunomide, which has to be discontinued for 8 weeks prior to baseline unless a cholestyramine washout has been performed. 8. Patients taking systemic corticosteroids have to be on a stable dose of = 10 mg/d prednisone or equivalent for at least 4 weeks before randomization. 9. Patients who are regularly taking NSAIDs (e.g., COX-1 or COX-2 inhibitors) are required to be on a stable dose for at least 2 weeks before 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. 1. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment. 2. Patients who have ever received biologic immunomodulating agents, e.g., anti-TNFa or anti-IL-6 therapeutic antibodies, or any cell-depleting therapies including but not limited to anti-CD20, or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD3, anti-CD19). 3. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes. 4. RA patients functional status class IV according to the ACR 1991 revised criteria. 5. Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, or morphine). 6. Any therapy by intra-articular injections (e.g., corticosteroid, hyaluronan) required for treatment of arthritis within 4 weeks before randomization. 7. Any intramuscular corticosteroid injection within 4 weeks before randomization. 8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG serumtest. 9. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (excluding systemic hormonal contraceptives) during dosing of study treatment and for additional 2 days (= 5 times the terminal half-life) of study medication. 10. History of malignancy, 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed. 11. Significant medical problems or diseases, including but not limited to: uncontrolled hypertension (= 160/95 mmHg), congestive heart failure [NYHA class III or IV], renal trauma, glomerulonephritis, one kidney only, a serum creatinine level exceeding 1.5 mg/dL (132.6 µmol/L). 12. Uncontrolled diabetes mellitus (IDDM or NIDDM) or a high risk for diabetes, as guided by following criteria: a. Clinically significant elevations of overnight fasted morning glucose levels b. HbA1c > 7.5% 13. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests such as AST, ALT, alkaline phosphatase, or serum bilirubin, guided by the following criteria. a. Any single parameter may not exceed 2 x ULN. A single parameter > 2 x ULN should be re-checked once, to rule out lab error. b. If the total bilirubin is > 2 x ULN, total bilirubin to be differentiated into direct/indirect reacting bilirubin. In any case, serum bilirubin should not exceed 1.6 mg/dL . 14. History of ongoing, chronic or recurrent infectious disease 15. History or evidence of active or latent tuberculosis at screening: a. PPD tuberculin skin test reaction of 10 mm diameter at screening or < 6-month prior to screening visit. Patients who have a positive PPD skin test with a documentation of BCG vaccination, who are at low environmental risk for tuberculosis (TB) infection or reactivation, and have a negative chest X-ray not older than 6 month can be included. b. For sites using QuantiFeron test, a positive test at screening or within 6 month prior to the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to demonstrate that the efficacy of 50 mg or 25 mg bid QAL964 at week 12 is superior to placebo in patients with active RA on a stable dose of MTX, based on the proportion of patients achieving an ACR20 response.;Secondary Objective: The key secondary objective is to evaluate the safety and tolerability of QAL964 in comparison to placebo in terms of incidences of AEs, laboratory abnormalities, vital signs and ECG. Further secondary objectives are 1. To evaluate the ACR20, ACR50 and ACR70 responses at Week 2, 4, 8 and 12 during QAL964 dosing versus placebo. 2. To evaluate the HAQ-;Primary end point(s): ACR20 response.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): safety and tolerability of QAL964 in comparison to placebo in terms of incidences of AEs, laboratory abnormalities, vital signs and ECG. Further secondary objectives are 1. To evaluate the ACR20, ACR50 and ACR70 responses at Week 2, 4, 8 and 12 during QAL964 dosing versus placebo. 2. To evaluate the HAQ-DI at Week 2, 4, 8 and 12 in patients receiving QAL964 versus placebo treatment.;Timepoint(s) of evaluation of this end point: Weeks 2, 4, 8, 12 | — |
Countries
Hungary, Russian Federation, Ukraine
Contacts
Public ContactPublic Information Desk
Novartis Hungary Kft. Pharma
Outcome results
None listed