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A Single Centre, Open-Label, Randomised, Study to Evaluate the Effect of Anakinra (r-metHuIL-1ra) Alone and in Combination With PEGylated Recombinant Methionyl Human Soluble Tumour Necrosis Factor Receptor Type I (PEG sTNF-RI) on Synovial Inflammation in Subjects With Rheumatoid Arthritis.


Phase 2
18 Years
N/A
Not Enrolling
Both
Rheumatoid Arthritis

Thank you

Trial Information

A Single Centre, Open-Label, Randomised, Study to Evaluate the Effect of Anakinra (r-metHuIL-1ra) Alone and in Combination With PEGylated Recombinant Methionyl Human Soluble Tumour Necrosis Factor Receptor Type I (PEG sTNF-RI) on Synovial Inflammation in Subjects With Rheumatoid Arthritis.


Inclusion Criteria:



- Diagnosed with RA as determined by American College of Rheumatology (ACR) criteria
(Appendix C)

- Disease duration of no less than 12 weeks of diagnosis confirmed by physician and
source documentation

- Disease duration < 10 years

- Active RA at baseline as defined by a minimum of 6 or more swollen joints and 9 or
more tender/painful joints (based on a 66/68-joint count excluding distal
interphalangeal joints) at screening and baseline,

And

- C-reactive protein (CRP) > 2 mg/dL at screening.

- Have active clinical synovitis in the knee as determined by the investigator based on
clinical evaluation

- 18 years of age or older

- Men or non-pregnant (negative serum HCG at screening unless surgically sterile or
postmenopausal), non-breast-feeding women may be enrolled. Females of childbearing
potential and males must use adequate contraceptive precautions as determined by the
principal investigator.

- Subjects that have taken any DMARD for less than 3 months must not have taken DMARDs
within 4 weeks prior to screening. Subjects that have taken any DMARD for longer than
3 months must not have taken DMARDs within 6 months of screening.

- Subject's doses of NSAIDs and oral corticosteroids (10 mg/day of prednisone or
equivalent) must have been kept stable for 4 weeks before screening

- Subjects must not have had intrarticular injections in the joint that will be
arthroscoped for at least 3 months prior to screening.

Before any study specific procedure or screening is done, the subject or legally
acceptable representative must give informed consent for participation in the study (see
Section 12.2). Before buccal smears and blood samples are taken for genetic testing, the
subject or legally acceptable representative must give informed consent for use of those
samples for genetic testing (see Section 12.2).

Exclusion Criteria:

- ACR functional class IV or American Rheumatology Association anatomical stage IV (see
Appendix C)

- Disease duration >10 years

- Diagnosed with the following:

Felty's syndrome

Advanced or uncontrolled Diabetes Mellitus (defined as: HbA1c > 8%, peripheral neuropathy,
renal/retinal involvement, or vascular disorders)

Malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the
cervix, within the past five years

Any other major chronic inflammatory disease or syndrome (e.g., psoriatic arthritis,
spondyloarthropathy, inflammatory bowel disease, fibromyalgia that required treatment in
the last year)

- Any uncontrolled, clinically significant systemic disease

- Pre-existing or recent onset central nervous system demyelinating disorders

- Significant hematologic abnormalities

- A history of drug or alcohol abuse within the previous 24 weeks

- Known to be hepatitis B surface antigen, hepatitis C virus or Human Immunodeficiency
Virus positive

- Any disorder that compromises ability to give informed consent for participation in
this study

- Is expected to require a major surgical operation while on study that would interfere
with the collection of the required assessments.

- Has an infection requiring systemic anti-infective therapy, open wounds, or has
developed frequent acute or chronic infections during the past 12 weeks.

- Prior active tuberculosis.

- Total white blood cell count < 3.5 x 109/L at screening

- Neutrophil count of < 2.5 x 109/L at screening

- Platelet count of < 125 x 109/L at screening

- Hemoglobin < 8.0 g/dL at screening

- Abnormal liver function tests (AST/ALT > 1.5 x the upper limits of normal) at
screening

- Abnormal renal function (serum creatinine > 1.5 x the upper limits of normal) at
screening

- Prior treatment with any protein-based TNF inhibitor (e.g. etanercept, infliximab,
PEG sTNF-RI, D2E7)

- Prior treatment with anakinra

- Receiving or has received any investigational drug within the previous 16 weeks or
within at least 5 half-lives of any investigational drug, whichever is greater (or is
currently using an investigational device)

- Received any intra-articular injections (e.g.. corticosteroids, hyaluronate
preparations) or systemic corticosteroid injections within 4 weeks before the
screening visit

- Requires analgesia other than paracetamol, NSAIDs, codeine, oxycodone, propoxyphene,
tramadol, hydrocodone, or the combinations of these products (or equivalents)

- Subject (men or women of childbearing potential) is not using adequate contraceptive
precautions as determined by the principal investigator

- Known allergy to E coli-derived products

- Not available for follow-up assessments

- Concerns for the subject's compliance with the protocol procedures

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Primary efficacy endpoint is the change from baseline at weeks 4, 26 and 52 in levels of select markers of inflammation (CD3 and CD 68) and destruction (MMP-1 and TIMP-1) in the synovium

Outcome Time Frame:

up to 52 weeks

Safety Issue:

No

Principal Investigator

MD

Investigator Role:

Study Director

Investigator Affiliation:

Amgen

Authority:

Ireland: Irish Medicines Board

Study ID:

20000211

NCT ID:

NCT00537667

Start Date:

August 2001

Completion Date:

June 2003

Related Keywords:

  • Rheumatoid Arthritis
  • IL-1ra
  • PEG sTNF-RI
  • Synovial biopsy
  • Inflammation
  • Bone and Cartilage Destruction
  • Rheumatoid Arthritis
  • Arthritis
  • Arthritis, Rheumatoid
  • Inflammation

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