Early Rheumatoid Arthritis in adults MedDRA version: 8.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis
Conditions
Interventions
Product Code: ACZ885
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: ACZ885 Drug Substance
Current Sponsor code:
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female patients of 18 to 75 years of age (inclusive) 2. Patient has a recent definite diagnosis of RA (less than 3 years since diagnosis), classified by ARA (1987 revised criteria 3. Candidate for methotrexate or biologic due to erosive arthritis, with no contraindications to such therapy, including: • Negative tuberculin skin test reaction (PPD 5 TU or as according to local standard practice) ( 1.0 mg/dL, and/or ESR > 28 mm/h. 6. At Screening, and Baseline, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed after the patient has rested for at least 3 minutes, and again when required after 3 minutes in the standing position. Vital signs should be within the following ranges: • young subjects: oral body temperature between 35.0-37.5 °C systolic blood pressure, 90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, 40 - 90 bpm • elderly subjects (60-75 years of age): oral body temperature between 35.0-37.5 °C systolic blood pressure, 100-160 mm Hg diastolic blood pressure, 50-100 mm Hg pulse rate, 50 - 100 bpm 7. Women of child-bearing potential may participate if they have a negative pregnancy test at screening and prior to dosing, and are willing to practice double-barrier contraception during the study, i.e. intra-uterine device plus condom, or spermicidal gel plus condom, from the date of screening and for at least 3 months following last study drug administration. Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior to inclusion. Menopause will be confirmed by a plasma FSH level of >40 IU/L. Surgically sterilized women must have been sterilized at least 6 months prior to screening. Surgical sterilization procedures must be supported with clinical documentation made available to sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. Male patients must be using a double-barrier local contraception, i.e., spermicidal gel plus condom, for the entire duration of the study, up to Study Completion visit, and refrain from fathering a child in the 3 months following last study drug administration. 8. - 11. See Protocol
Exclusion criteria
Exclusion criteria: 1. Contraindication for MRI of wrist. 2. Patients with magnetizable metal parts/devices on and in the body that could interfere with the interpretation of the MRI 3. Patients with an unstable active medical condition likely to impair evaluation of safety and biomarker results. 4. Previous treatment with biological therapy or MTX. 5. limited kidney function (creatinin clearance under 60 ml/min) 6. Previous treatment with other disease-modifying anti-rheumatic drugs (DMARDS) such as sulfasalazine, hydroxychloroquine within 4 weeks of screening. 7. Intra-articular corticosteroids within 4 weeks prior to screening. 8. Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulations, and for any other limitation of participation based on local regulations. 9. Donation or loss of 400 mL or more of blood within 8 weeks prior to first dosing, or longer if required by local regulation. 10. Significant illness within two weeks prior to dosing. 11. A past medical history of clinically significant ECG abnormalities or a family history grandparents, parents and siblings) of a prolonged QT-interval syndrome. 12. History of autonomic dysfunction (e.g. history of fainting, orthostatic hypotension, sinus arrhythmia). 13. History of clinically significant acute or chronic bronchospastic disease (including asthma and chronic obstructive pulmonary disease, treated or not treated). 14. History of clinically significant drug allergy or history of atopic allergy (asthma, urticaria, eczematous dermatitis). A known hypersensitivity to the study drug or drugs similar to the study drug. 15. History of disease of the blood building system 16. History of serious or active infections 17. History of gastric ulcers 18. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs or which may jeopardize the patient in case of participation in the study. The investigator should be guided by evidence of any of the following: • history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding; • history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; • history or clinical evidence of pancreatic injury or pancreatitis; • clinical evidence of liver disease or liver injury as indicated by abnormal liver function tests such as AST, ALT, GGT, alkaline phosphatase, or serum bilirubin. If the total bilirubin concentration is increased above 1.5 times the upper normal limit total bilirubin should be differentiated into the direct and indirect reacting bilirubin. • history or presence of impaired renal function as indicated by clinically significantly abnormal creatinine clearance. • evidence of urinary obstruction or difficulty in voiding at screening; 19. History of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) test result. 20. A positive Hepatitis B surface antigen (HBsAg) or Hepatiti
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ACZ885 plus methotrexate (MTX) by assessing the response to treatment (ACR50) as compared to MTX alone in early rheumatoid arthritis patients after 6, 14, and 26 weeks of treatment; Secondary Objective: evaluate efficacy of ACZ885 plus MTX by assessing the response to treatment (ACR20, 70, and 90) compared to MTX alone in early RA patients after 6, 14 and 26 weeks of treatment establish a biomarker profile including genomics, cytomics and biochemical markers of bone and cartilage turn over to dissect responders (ACR20) versus non-responders to ACZ885 plus MTX treatment after 6, 14 and 26 weeks of treatment. establish a biomarker profile including genomics, cytomics and biochemical markers of bone and cartilage turn over to dissect high-responders (ACR50) versus non-responders to ACZ885 plus MTX treatment after 6, 14 and 26 weeks of treatment for other secondary EPs see protocol ;Primary end point(s): See E.3 | — |
Countries
Belgium, Germany, Italy, Netherlands
Outcome results
None listed