The purpose of this study is to evaluate the effiacy (improvement of signs and symptoms) and safety of an antibody to IL-12 and IL-23 [CNTO 1275] in psoriatic arthritis.

Condition	Intervention	Phase
Psoriatic Arthritis;	Drug: CNTO 1275, monoclonal antibody to IL-12p40 and IL-23 p40 subunits	Phase II

Further study details as provided by Centocor, Inc.:

Primary Outcomes: The primary endpoint of this study is to see whether a greater number of subjects who receive 4 doses of CNTO 1275 90 mg have 20% (or more) improvement from baseline in their American College of Rheumatology arthritis scores at Week 12
Secondary Outcomes: Secondary outcomes are to see whether more subjects treated with CNTO 1275 have 50% or 70% improvement in arthritis scores, improvements in quality of life assessments and greater numbers of subjects with 75% improvement in psoriasis scores at Week 12.
Expected Total Enrollment:  140

While anti-TNF molecules and other disease modifying agents show effectiveness in patients with psoriatic arthritis, there are reasons to study new agents targeting different areas of inflammation. Also, there is potential to improve the response further over available therapy and to treat patients who do not repond to the available therapies. There is considerable evidence of the role of IL-12, in the development and worsening of experimental animal arthritis models. Studies in humans have suggested a role for IL-12 as causing worsening arthritis. Hence the scientific question to be asked is whether blocking IL-12 and IL-23 with antibodies will lead to improvement in both arthritis and psoriasis skin lesions in subjects with psoriatic arthritis. Improvement of psoriasis with CNTO 1275 has been demonstrated in a Phase II study.This study is a randomized, double blind, parallel-group, muticenter study to evaluate the effectiveness and safety of CNTO 1275 compared to placebo in the treatment of subjects with active psoriatic arthritis. The primary effectiveness endpoint will be measured by the reduction in signs and symptoms of arthritis, as defined by 20% improvement from baseline ACR measurements of arthritis at Week 12. The study will additionally look at higher levels of joint improvement (i.e. 50% or 70% improvement from baseline, improvements in skin lesions, improvement in activity and quality of life), as well as the impact of CNTO1275 on psoriatic skin lesions and quality of life Subjects who qualify by fulfilling all inclusion and exclusion criteria listed below will come to their site for a screening evaluation which includes testing for tuberculosis (skin test and chest x-ray). Subjects will be asked to give consent to participate in the study prior to any study specific procedures and will then have full medical histories taken and physical examinations, including height, weight and vital signs. Appropriate blood tests and pregnancy tests if applicable will be performed. If the subject fulfills all of these examinations and is thought to be a candidate for this study, they will be entered in the study at the judgement of the investigator at the site.

Seventy subjects will receive CNTO 1275 90 mg subcutaneously (under the skin) at Weeks 0,1,2 and 3. They will then receive placebo subcutaneous injections at Weeks 12 and 16. Seventy subjects will receive placebo injections at Weeks 0, 1,2 and 3 and CNTO 1275 90 mg subcutaneously at Weeks 12 and 16.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Active Psoriatic arthritis (for at least 6 months prior to administration of first study injection) as defined as having:

  • 3 or more swollen joints and 3 or more tender joints and at least one of the following
  • Morning stiffness of >=45 minutes, or
  • CRP >=1.5 mg/dl
• Active plaque psoriasis (defined as a target lesion of at least 2 cm in diameter), but not in armpits, on chest between breasts or groin.
• At least one of the Psoriatic arthritis subsets - distal interphalangeal joint involvement, polyarticular arthritis, arthritis mutilans, asymmetric peripheral arthritis or ankylosing spondylitis-like arthritis.
• Negative Rheumatoid Factor blood test
• Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must agree to continue to use such measures until 12 months after receiving the last injection of study agent.
• Able to adhere to the study visit schedule and other protocol requirements.
• Capable of giving informed consent and the consent must be obtained prior to any study related procedures.
• Must avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during study.
• Have active arthritis despite DMARDs (disease modifying agents such as leflunomide, gold, sulfasalazine but not including methotrexate) or NSAID (non-steroidal anti-inflammatory agents such as aspirin, ibuprofen, naproxen) therapy. DMARD therapy is defined as taking a DMARD for at least 3 months, or evidence of not tolerating DMARD . NSAID therapy is defined as taking an NSAID for at least 4 weeks
• If using methotrexate, subjects should have started treatment at least 3 months prior to the first administration of study agent and should have no serious toxic side effects attributable to methotrexate. Methotrexate route of administration and doses (not to exceed 25 mg/week) should be stable for at least 4 weeks prior to the randomization visit.
• If using NSAIDS, must be on a stable dose for at least 2 weeks prior to the randomization visit.
• If using oral corticosteroids, the subject must be on a stable dose equivalent to <= 10 mg of prednisone/day for at least 2 weeks prior to the first administration of study agent. If currently not using corticosteroids, the subject must have not received oral corticosteroids for at least 2 weeks prior to the randomization visit.
• Must agree not to receive a live virus (example: influenza vaccine) or live bacterial vaccination (example: BCG vaccination) during the trial or up to 12 months after the last study injection.

• Are considered eligible according to the following tuberculosis (TB) screening criteria:

  1. Have no history of latent or active TB prior to screening.
  2. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
  3. 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 or simultaneously with the first administration of study agent.
  4. Within 1 month prior to the first administration of study agent, either have a negative tuberculin skin test, or have a newly identified positive tuberculin skin test 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.
  5. Have a chest X-ray, 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.

Exclusion Criteria:

• Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled in the study and agree not to become pregnant or plan a pregnancy within 12 months after the last dose of CNTO 1275.
• Have used any therapeutic agent targeted at reducing IL-12 or IL-23.
• Have received DMARDs other than MTX within 4 weeks prior to the randomization visit.
• Have used any investigational drug within the previous 4 weeks or 5 times the half-life of the investigational agent, whichever is longer. (ask your doctor)
• Have used any biologic within the previous 3 months or 5 times the half-life of the biologic, whichever is longer. (ask your doctor)
• Have received leflunomide within 4 weeks prior to the first infusion (irrespective of undergoing a drug elimination procedure), or have received leflunomide within 3 months prior to the first infusion and have not undergone a drug elimination procedure.
• Have received any oral, intravenous or intramuscular medications/treatments that could affect psoriasis (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, hydroxyurea, fumaric acid derivatives, or phototherapy) within 4 weeks of the randomization visit.
• Have used topical medications/treatments that could affect psoriasis (eg, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens) within 2 weeks of the randomization visit.
• Have used any oral, intravenous or intramuscular immunosuppressants (such as cyclosporine) within 4 weeks of the randomization visit.
• Have received intra-articular (in the joint), intramuscular (in the muscle), or Intravenous corticosteroids, including adrenocorticotropic hormone administered intramuscularly during the 4 week prior to the randomization visit.
• Are currently receiving lithium or have received lithium within 4 weeks of the randomization visit.
• Have received a live virus or bacterial vaccination within 3 months prior to first injection and agree not to receive a live virus or bacterial vaccination during the trial or up to 12 months after the last injection.
• Have had a BCG vaccination within 12 months of screening. Subject must agree not to receive a BCG vaccination during the trial or up to 12 months after the last injection.
• Have a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin wounds or ulcers.
• Have a history of an infected joint prosthesis, or have received antibiotics for a suspected infection of a joint prosthesis, if that prosthesis has not been removed or replaced.
• Have had or have a serious infection (eg, sepsis, pneumonia or pyelonephritis), or have been hospitalized or received IV antibiotics for an infection during the 2 months prior to screening.
• Are considered ineligible according to the TB eligibility assessment, screening, and prevention rules. (delete since we have 13, 14, and 15 below –from TB template.)
• Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
• Have a chest radiograph within 3 months prior to the first administration of study agent that shows an abnormality suggestive of a malignancy, current active infection, including TB or fibrosis.
• Have had a significant infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.
• Have or have had a herpes zoster infection within 2 months of randomization.
• Are known to be infected with human immunodeficiency virus, hepatitis B, or hepatitis C.
• Have current signs or symptoms of severe, progressive, or uncontrolled kidney, liver, blood, intestinal, hormonal, lung, heart, nervous, brain, or psychiatric disease.
• Have a transplanted organ (with exception of a corneal transplant > 3 months prior to randomization).
• Have a known history of blood diseases, including lymphoma, or signs and symptoms suggestive of possible blood diseases, such as enlarged lymph nodes of unusual size or location.
• Have any known cancer or have a history of cancer within the previous 5 years (with the following exceptions: have had basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been treated with no evidence of recurrence; have not been treated with phototherapy and have had no more than 1 squamous cell carcinoma of the skin that has been treated with no evidence of recurrence).
• Have a history of asthma or suspected asthma 

Please refer to this study by ClinicalTrials.gov identifier  NCT00267956

Study ID Numbers:  CR006322; C0743T10
Last Updated:  December 21, 2005
Record first received:  December 20, 2005
ClinicalTrials.gov Identifier:  NCT00267956
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-01-10