| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Seronegative oligoarthritis (inflammatory arthritis of 4 active joints or less) |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary question is what is the optimal treatment for patients with resistant oligoarthritis. The primary outcome is reduction in synovitis seen on US scan at 8 weeks following administration of IA steroid (standard care), IA infliximab or IV infliximab. |
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| E.2.2 | Secondary objectives of the trial |
Secondary outcomes in this study include changes in clinical and imaging disease activity measured by:
change in ultrasound synovitis score of the knee (0, 2 and 16 weeks)
change in pain scores (0, 2, 6, 8, 16, 26 weeks)
RAOS (0, 2, 6, 8, 16, 26 weeks)
PsQOL (0, 2, 6, 8, 16, 26 weeks)
|
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Seronegative Oligoarthritis of the Knee Study (SOKS) Biological Sub-Study. Protocol within main protocol v1 12/10/09, separate information and consent form v1 12/10/09 |
|
| E.3 | Principal inclusion criteria |
1. Inflammatory oligoarthritis (4 or less active joints) with at least one swollen knee joint of at least 3 months duration
2. Rheumatoid factor and anti-CCP Ab negative
3. Either arthritis onset at <45 years of age, or arthritis onset at ≥45 years of age with EMS>30mins or raised inflammatory markers
4. If under 40 years of age, clinical exclusion of a diagnosis of gout.
5. If 40 years or older at screening, a prior normal examination of synovial fluid from the affected joint excluding crystal arthropathy or infection.
6. Failure of methotrexate (inefficacy after >3 month trial, intolerance or contra-indication)
7. Have the capacity to understand and sign an informed consent form.
8. Gender: male or female
9. Age: 18 to 70 years of age.
10. Women must be either postmenopausal (no menstrual period for a minimum of 1 year) or surgically sterilized or in use of adequate birth control measures and have a negative serum pregnancy test on entry in the study. Men must agree to use adequate birth control during the study for 6 months after the infusion of study agent.
11. Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
12. Are considered eligible according to the tuberculosis (TB) eligibility assessment, screening, and early detection of reactivation rules defined in Section on: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation Rules
13. The screening laboratory test results must meet the following criteria
• WBC (white blood cell count): >3.5 x 109/L
• ANC (absolute neutrophil count): >1.5 x 109/L
• Hemoglobin: >8.5 x 109/L
• Platelets: >100 x 109/L
• SGPT (ALT – alanine aminotransferase) < 1.5 times upper normal limit
14. Have no history of latent or active TB prior to screening. [An exception is made for subjects with a history of latent TB and documentation of having completed appropriate treatment for latent TB within 3 years prior to the first administration of study agent. It is the responsibility of the investigator to verify the adequacy of previous anti-tuberculous treatment and provide appropriate documentation.]
15. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
16. Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to the first administration of study agent.
17. Within 6 weeks prior to the first administration of study agent, either have a negative QuantiFeron test result or have a newly identified positive QuantiFeron test result during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent.
18. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current, active TB or old, inactive TB.
|
|
| E.4 | Principal exclusion criteria |
If a subject has any of the following criteria, he or she may not be enrolled in the study:
1. Grade 4 osteoarthritis (Kellgren-Lawrence score) on plain radiograph of the knee
2. Rheumatoid Arthritis (defined by the ACR criteria for the diagnosis of RA, 1987)
3. Ankylosing Spondylitis (defined by the modified New York Criteria)
4. Clinical diagnosis of gout or previous evidence of crystal arthropathy on synovial fluid aspirates
5. Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion (this includes father's who plan on fathering a child within 6 months after their last infusion).
6. Have had any previous treatment with biological therapies.
7. History of receiving human/murine recombinant products or a known allergy to murine products. A known allergy to murine product is definitely an exclusion criterion
8. Documentation of seropositive for human immunodeficiency virus (HIV).
9. Documentation of a positive test for hepatitis B surface antigen or hepatitis C.
10. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results.
11. Have a known history of serious infections (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
12. Have or have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening
13. Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.Are considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in Section on: Tuberculosis Eligibility Assessment, Screening, and Early Detection of Reactivation Rules
14. Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy or current active infection, including TB.
15. Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g., nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly.
16. Currently have any known malignancy other than the condition being treated or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
17. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.]
18. Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
19. Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).Have a concomitant diagnosis or history of congestive heart failure.
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|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the change in ultrasound synovitis score of the knee at 8 weeks. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| IA vs IV infliximab vs IA steroid (standard care) |
|
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of trial is last patient, last visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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