Onercept in the Treatment and Re-Treatment of Subjects With Moderate to Severe Plaque Psoriasis

Study Overview
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Brief Summary
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The is a double-blind, placebo-controlled, randomized, and multicenter study consisting of a first treatment (FT) period followed by either an observation (OB) period and a re-treatment (RT) period or an open-label (OL) treatment period, depending on FT period response, and a 4-week safety follow-up (FU) period. The purpose of this study is to evaluate the safety and efficacy of onercept, to be administered as 150 milligram (mg) three times a week, compared to matching placebo, for the induction of remission in subjects with moderate to severe plaque psoriasis.

Official Title
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A Multicentre, Randomised, Double-blind, Placebo Controlled Phase III Study of Subcutaneously Administered Onercept in the Treatment and Re-treatment of Subjects With Moderate to Severe Plaque Psoriasis

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Drug: Onercept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent, given prior to any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care At least 18 years of age Female subjects must be neither pregnant nor breast-feeding, and must lack childbearing potential, as defined by either: Being post-menopausal (that is at least 12 months passed last menses) or surgically sterile, or Using an effective form of contraception (that is, condoms, oral contraceptives or intrauterine device) (Confirmation that the subject is not pregnant must be established by a negative urinary human chorionic gonadotrophin test within 7 days before Study Day 1. A pregnancy test is not required if the subject is post-menopausal or surgically sterile) An out-patient status at the time of enrollment Plaque psoriasis for at least 12 months Plaque psoriasis covering at least 10 percent of total body surface area and a PASI score of 12.0 or more Candidate for phototherapy or systemic therapy Static Physician's Global Assessment (sPGA) of 3 or more Exclusion Criteria: Use of more than one Non-steroidal anti-inflammatory drug (NSAID) to treat psoriatic arthritis or having a change in chronic NSAID regimen during the 28 days before Study Day 1 to treat psoriatic arthritis Previous systemic treatment with biologics, including interferon, and/or cytokines/anti cytokines (for example, anti- tumor necrosis factor-alpha, anti-cluster of differentiation [CD]4, interleukin [IL]-10, IL-1ra, anti-CD11a, etc.) within 3 months before Study Day 1 Participation in any other investigational study or experimental therapeutic procedure considered to interfere with the study within 3 months before Study Day 1 Treatment with any systemic corticosteroids or intra-articular corticosteroid injection during the 28 days before Study Day 1 Experimental or off-label treatments for psoriasis and/or psoriatic arthritis such as azathioprine, hydroxyurea / hydroxycarbamide, mycophenolate, chlorambucil, leflunomide or cyclophosphamide within 1 year prior to Study Day 1 Treatment with cyclosporin, methotrexate, oral retinoids (that is, acitretin), or fumaric acid esters within 28 days (3 months for acitretin) before Study Day 1 Treatment with any topical therapies, such as Vitamin D derivatives, corticosteroids, tars and tar oils, dithranol for chronic or short contact therapy, salicylic acid and topical retinoids, within 14 days before Study Day 1 Phototherapy within 28 days before Study Day 1 Use of tanning booths within 14 days before Study Day 1 Abnormal liver function, defined by a total bilirubin greater than or equal to 1.2 times the upper limit of normal values, (except in the case of Gilbert's syndrome), or aspartate aminotransferase, alanine aminotransferase or alkaline phosphatase levels greater than or equal to 2.5 times the upper limit of normal values Inadequate bone marrow reserve, defined as: Leukocytes less than or equal to 3.5 * 10^9 per liter (/L), or Thrombocytes less than or equal to 100 * 10^9 /L, or Hemoglobin less than or equal to 5 millimole per liter (mmol/L) (8.9 gram per deciliter). Abnormal renal function, defined by serum creatinine greater than 150 micromole per liter. Sero-positivity for human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) Planned major surgery within the treatment period of the study. History of cancer in the preceding 5 years (except adequately treated basal cell carcinoma of the skin or squamous cell carcinoma in situ of the skin). Any history of hematopoietic cancer History of active tuberculosis, current active tuberculosis or candidacy for prophylactic therapy for tuberculosis Active severe infection (or non-severe infection at the discretion of the Investigator). History of any opportunistic infection (for example, viral, fungal, protozoal, or bacterial) in the 6 months preceding Study Day 1 related to any clinical condition of immunodeficiency Clinically significant and serious abnormalities on electrocardiography or chest X-ray, (at the discretion of the Investigator) Other serious concomitant disorders incompatible with the study. In particular, subjects with congestive heart failure, prior or current history of blood dyscrasia or central nervous system demyelinating disorders should not be included in the study History of or current drug (including narcotics) abuse, or current active problems with alcohol abuse Requirement for immunization, allergy desensitization or vaccination during the entire study period (it is recommended that these procedures be scheduled at least 14 days prior to Study Day 1 or greater than 3 months after the last injection of study drug), with the exception of killed influenza vaccines which are allowed at any time during the study Guttate, erythrodermic or pustular psoriasis as sole or predominant form of psoriasis. Evidence of skin conditions other than psoriasis (for example, eczema) that would interfere with psoriasis disease assessments Clinically significant psoriasis flares during screening or at the time of enrollment necessitating immediate relief (at the Investigator's discretion) Live or killed virus or bacteria vaccines (within 14 days before Study Day 1) with the exception of killed influenza vaccines which are allowed both prior to Study Day 1 and at any time during the study Bedridden status Previous use of onercept

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Onercept<br> | Drug: Onercept<br>* Onercept will be administered subcutaneously three times a week at a dose of 150 mg, for 12 weeks of first treatment (FT) period. Subjects showing 75 percent improvement in PASI score at Week 12 will be observed for 24 weeks without treatment or until relapse, whichever occurs first. Subjects then will be reassigned to either Onercept (150 mg) or placebo, subcutaneously three times a week, for 16 weeks. Subjects not showing 75 percent improvement in PASI score at Week 12 will receive only Onercept (150 mg) subcutaneously three times a week, for 40 weeks as open-label treatment.<br>* Other names: recombinant human tumor necrosis factor binding protein-1 (r-hTBP-1);|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching Placebo will be administered subcutaneously three times a week, for 12 weeks in the FT period. Subjects showing 75 percent improvement in PASI score at Week 12 will be observed for 24 weeks without treatment and then again assigned to either placebo or Onercept (150 mg), subcutaneously three times a week, for 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with at least a 75 percent improvement in Psoriatic Area and Severity Index (PASI) score at Week 12 |  | Week 12 | 
| Percentage of subjects with at least a 75 percent improvement in Psoriatic Area and Severity Index (PASI) score at Week 52 |  | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects attaining a Physician's Global Assessment (PGA) rating of Cleared or Almost Cleared at Week 12 |  | Week 12 | 
| Mean percentage improvement in Psoriatic Area and Severity Index (PASI) Score |  | Baseline up to Week 12 | 
| Percentage of subjects with at least a 90 percent improvement in the Psoriatic Area and Severity Index (PASI) score |  | Baseline up to Week 12 | 
| Mean percentage improvement in the itching scale |  | Baseline up to Week 12 | 
| Change from Baseline in Mean improvement of Dermatology Life Quality Index (DLQI) quality of life assessment at Week 12 |  | Baseline and Week 12 | 
| Median time to relapse |  | Week 12 up to Week 36 | 
| Percentage of subjects attaining a Physician's Global Assessment (PGA) rating of Cleared or Almost Cleared at Week 52 |  | Week 52 | 
| Mean percentage improvement in Psoriatic Area and Severity Index (PASI) Score |  | Baseline up to Week 48 | 
| Mean percentage improvement in Psoriatic Area and Severity Index (PASI) Score up to Week 52 |  | Baseline up to Week 52 | 
| Mean Psoriatic Area and Severity Index (PASI) score |  | Week 36 up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Placebo, Psoriatic Arthritis, Moderate plaque psoriasis, severe plaque psoriasis, Onercept