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

Arthritis, Psoriatic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00090129
• Other study ID #: 24979
• Status: Terminated
• Phase: Phase 3
• First received: August 24, 2004
• Last updated: October 21, 2013
• Start date: September 2004
• Est. completion date: June 2005

Study information

• Verified date: October 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 854
• Est. completion date: June 2005
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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any study-related procedure not part of the subject's normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his or her future medical care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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis, Psoriatic
• Psoriasis

Intervention

Drug:
• Onercept
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.
• Placebo
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.

Locations

Country	Name	City	State
Canada	Probity Medical Research	Edmonton	Alberta
Canada	Guenther Dermatology Research Center	London	Ontario
Canada	Probity Medical Research	Waterloo	Ontario
United States	Academic Dermatology Associates	Albuquerque	New Mexico
United States	Atlanta Dermatology Vein & Research Center	Alpharetta	Georgia
United States	University of Michigan Department of Dermatology	Ann Arbor	Michigan
United States	DermResearch Inc	Austin	Texas
United States	Scott D. Glazer, MD	Buffalo Grove	Illinois
United States	Midwest Cutaneous Research Corporation	Clinton Township	Michigan
United States	Texas Dermatology Research Institute	Dallas	Texas
United States	Cherry Creek Research, Inc.	Denver	Colorado
United States	Colorado Medical Research Center	Denver	Colorado
United States	Associates in Research Inc.	Fresno	California
United States	Minnesota Clinical Study Center	Fridley	Minnesota
United States	Rivergate Dermatology	Goodlettsville	Tennessee
United States	Center for Clinical Studies	Houston	Texas
United States	Center For Clinical Studies	Houston	Texas
United States	University Texas M.D. Anderson Cancer Center	Houston	Texas
United States	University of California, Irvine	Irvine	California
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	North Florida Dermatology Associates, P.A.	Jacksonville	Florida
United States	Saint Mary's Centeral Wing Annex	Knoxville	Tennessee
United States	Therapeutics Clinical Research	La Jolla	California
United States	Bressnick Gibson Parker Dinehart Sangster Dermatology, P.A.	Little Rock	Arkansas
United States	Longmont Clinic PC	Longmont	Colorado
United States	International Dermatology Research	Miami	Florida
United States	Tennessee Clinical Research Center	Nashville	Tennessee
United States	The Savin Center P.C.	New Haven	Connecticut
United States	Virginia Clinical Research, Inc	Norfolk	Virginia
United States	Northwest Cutaneous Research Specialist	Portland	Oregon
United States	Oregon Medical Research Center, P.C.	Portland	Oregon
United States	University of California	San Francisco	California
United States	Clinical Research Specialists Inc.	Santa Monica	California
United States	Dermatology Associates P.L.L.C.	Seattle	Washington
United States	Rockwood Clinic, PS	Spokane	Washington
United States	Solano Clinical Research	Vallejo	California
United States	Dermatology Specialists Inc	Vista	California
United States	Dermatology Associates, P.C. at the Washington Hospital CTR	Washington	District of Columbia
United States	Piedmont Medical Research Associates	Winston Salem	North Carolina
United States	Wake Forest Univ School of Medicine	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Papp K. Clinical development of onercept, a tumor necrosis factor binding protein, in psoriasis. Curr Med Res Opin. 2010 Oct;26(10):2287-300. doi: 10.1185/03007995.2010.507492. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects with at least a 75 percent improvement in Psoriatic Area and Severity Index (PASI) score at Week 12		Week 12	No
Primary	Percentage of subjects with at least a 75 percent improvement in Psoriatic Area and Severity Index (PASI) score at Week 52		Week 52	No
Secondary	Percentage of subjects attaining a Physician's Global Assessment (PGA) rating of Cleared or Almost Cleared at Week 12		Week 12	No
Secondary	Mean percentage improvement in Psoriatic Area and Severity Index (PASI) Score		Baseline up to Week 12	No
Secondary	Percentage of subjects with at least a 90 percent improvement in the Psoriatic Area and Severity Index (PASI) score		Baseline up to Week 12	No
Secondary	Mean percentage improvement in the itching scale		Baseline up to Week 12	No
Secondary	Change from Baseline in Mean improvement of Dermatology Life Quality Index (DLQI) quality of life assessment at Week 12		Baseline and Week 12	No
Secondary	Median time to relapse		Week 12 up to Week 36	No
Secondary	Percentage of subjects attaining a Physician's Global Assessment (PGA) rating of Cleared or Almost Cleared at Week 52		Week 52	No
Secondary	Mean percentage improvement in Psoriatic Area and Severity Index (PASI) Score		Baseline up to Week 48	No
Secondary	Mean percentage improvement in Psoriatic Area and Severity Index (PASI) Score up to Week 52		Baseline up to Week 52	No
Secondary	Mean Psoriatic Area and Severity Index (PASI) score		Week 36 up to Week 52	No