A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Patients With Moderate to Severe Psoriasis

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects With Moderate to Severe Plaque-type Psoriasis.

The primary objective of this study is to evaluate the efficacy and safety of ustekinumab (CNTO 1275) in the treatment of patients with moderate to severe plaque psoriasis.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Placebo; Ustekinumab (CNTO 1275) 45 or 90 mg; Drug: Ustekinumab (CNTO 1275) 45 mg; Drug: Ustekinumab (CNTO 1275) 90 mg

Detailed Description

Although numerous therapeutic options exist for the treatment of psoriasis, there is still a significant unmet medical need due to the limited effectiveness and/or significant side effect profile of current treatment options. Preclinical studies and early phase clinical studies suggest that interleukins-12 and -23, two molecules that are part of the communication network in the immune system, may play an important role in psoriasis. Ustekinumab (CNTO 1275) is a monoclonal antibody directed against interleukins -12 and -23. This is a randomized (study drug assigned by chance like flipping a coin), double blind (neither physician nor patient knows the name of the assigned drug), parallel-group, multicenter study to determine the effectiveness and safety of two different doses of ustekinumab (CNTO 1275) administered subcutaneously (under the skin) as compared with placebo in patients with moderate to severe plaque-type psoriasis (the most common type of psoriasis). The hypothesis is that ustekinumab (CNTO 1275) will be more effective in treatment of psoriasis than placebo, that the improvement in psoriasis will result in an improved quality of life for treated patients and that ustekinumab (CNTO 1275) will be generally well tolerated. Patients will receive ustekinumab (CNTO 1275), 45 or 90 mg, or placebo administered subcutaneously at weeks 0 and 4 weeks then every 12 weeks thereafter until week 52. For patients who partially respond to the starting regimen, the dosing interval may be adjusted to every 8 weeks. Patients will enter long term extension portion of the study at week 52 during which patients will continue to receive treatment with ustekinumab (CNTO 1275) and will be followed for a total of up to 264 weeks from the initial (week 0) administration of study agent.

The dose of ustekinumab (CNTO 1275) will be 45 or 90 mg or placebo administered subcutaneously at weeks 0 and 4 weeks then every 12 weeks thereafter. For patients who partially respond to the starting regimen, the dosing interval may be adjusted to every 8 weeks.

• Study Type: Interventional
• Enrollment (Actual): 1230
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
  • Innsbruck, Austria
  • Wien, Austria
• Canada
  • Alberta
    • Calgary, Alberta, Canada
    • Edmonton, Alberta, Canada
  • British Columbia
    • Surrey, British Columbia, Canada
    • Vancouver, British Columbia, Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
  • Ontario
    • Barrie, Ontario, Canada
    • Hamilton, Ontario, Canada
    • London, Ontario, Canada
    • North Bay, Ontario, Canada
    • Toronto, Ontario, Canada
    • Waterloo, Ontario, Canada
    • Windsor, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
    • Sainte-Foy, Quebec, Canada
    • Sherbrooke, Quebec, Canada
• France
  • Nice, France
• Germany
  • Berlin, Germany
  • Brandenburg, Germany
  • Dresden, Germany
  • Erlangen, Germany
  • Frankfurt, Germany
  • Hamburg, Germany
  • Kiel, Germany
  • Mainz, Germany
  • Munchen, Germany
• Switzerland
  • Genève, Switzerland
  • Zurich N/A, Switzerland
• United Kingdom
  • London, United Kingdom
  • Salford, United Kingdom
  • Southampton Trials Carried Out, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • La Jolla, California, United States
    • Los Angeles, California, United States
    • San Diego, California, United States
  • Florida
    • Jacksonville, Florida, United States
    • Miami, Florida, United States
  • Illinois
    • Normal, Illinois, United States
    • Skokie, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Kentucky
    • Louisville, Kentucky, United States
  • Massachusetts
    • Andover, Massachusetts, United States
    • Boston, Massachusetts, United States
  • Michigan
    • Port Huron, Michigan, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • New Brunswick, New Jersey, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Winston Salem, North Carolina, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Plymouth Meeting, Pennsylvania, United States
  • South Carolina
    • Mt. Pleasant, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Houston, Texas, United States
    • San Antonio, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Plaque-type psoriasis diagnosed >= 6 months prior
• Plaque-type psoriasis covering at least 10% of total body surface areas
• Psoriasis area-and-severity index score of >=12 at screening and baseline
• Considered by treating dermatologist to be a candidate for phototherapy or systemic treatment of psoriasis
• Women of childbearing potential and all men must agree to use adequate birth control measures throughout the trials and for 12 months following the last injection of study agent
• Have no history of latent or active tuberculosis (TB)

Exclusion Criteria:

• Currently have nonplaque forms of psoriasis or drug-induced psoriasis
• Women who are pregnant or nursing, or men and women planning pregnancy while enrolled in the study
• Patients who have used any therapeutic agent targeted at reducing IL-12 or IL-23
• Patients who have had a Bacillus Calmette-Guerin (BCG) vaccination within the previous 12 months prior to screening
• Patients who have a history of chronic or recurrent infectious disease or who have or have had a serious infection requiring hospitalization or intravenous antibiotics within the previous 2 months prior to screening
• Patients who have or ever have had a nontuberculous mycobacterial infection or opportunistic infection
• Patients known to be infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Patients who have current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease
• Patients with a malignancy or who have a history of malignancy (with the exception of certain skin cancers and pre-invasive cervical cancer)
• Patients participating in another trial using an investigational agent or procedure
• Systemic immunosuppressants within 4 weeks of the first administration of study agent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group I: Placebo	Drug: Placebo; Ustekinumab (CNTO 1275) 45 or 90 mg; Placebo at Weeks 0 and 4 and blinded SC injections of ustekinumab, 45 or 90 mg, at Weeks 12 and 16; followed by a dosing regimen to be determined by patient's response status for Weeks 28 to 52; followed by unblinded dosing that may be adjusted at the investigator's discretion for Weeks 52 to 264
Experimental: Group II: Ustekinumab 45 mg	Drug: Ustekinumab (CNTO 1275) 45 mg; Ustekinumab, 45 mg, at Weeks 0 and 4 and every 12 weeks for Weeks 16 to 28. Followed by a dosing regimen to be determined by patient's response status for Weeks 28 to 52; followed by unblinded dosing that may be adjusted at the investigator's discretion for Weeks 52 to 264
Experimental: Group III: Ustekinumab 90 mg	Drug: Ustekinumab (CNTO 1275) 90 mg; Ustekinumab, 90 mg, at Weeks 0 and 4 and every 12 weeks for Weeks 16 to 28. Followed by a dosing regimen to be determined by patient's response status for Weeks 28 to 52; followed by unblinded dosing that may be adjusted at the investigator's discretion for Weeks 52 to 264

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Psoriasis Area and Severity Index (PASI) Score of 75 Percent or Above at Week 12	Number of participants achieving greater than or equal to 75 percent improvement in PASI at Week 12. PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).	Week 0 to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Physician Global Assessment (PGA) of Cleared or Minimal at Week 12	Number of participants achieving a physician global assessment (PGA) (0 [none] to 5 [severe]) of cleared or minimal at Week 12. The PGA is 7-point scale used in clinical trials of various diseases. In this the physician checks the state of the disease and gives them score from 0 (clear) to 5 (severe).	Week 12
Change in Dermatology Life Quality Index (DLQI) at Week 12	Change in Dermatology Life Quality Index (DLQI) from baseline at Week 12. The DLQI is a 10-item questionnaire, that in addition to evaluating overall quality of life, can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. Scores range from 0 (no impairment in quality of life) to 30 (most impairment in quality of life).	Baseline to Week 12
Number of Participants Visits With Psoriasis Area and Severity Index (PASI) 75 From Week 40 Through Week 52	Number of visits at which participants randomized at Week 28 achieved at least 75 percent improvement from baseline in PASI from Week 40 through Week 52 in participants randomized at Week 28. PASI is a widely used tool for the measurement of severity of psoriasis. This is a test of how bad a person's psoriasis is. The scale combines redness, scaling, and thickness, as well as overall body involvement to determine the PASI score. The scale ranges from 0 (best) to 72 (worst).	Week 40 to Week 52

Collaborators and Investigators

• Sponsor: Centocor Research & Development, Inc.

Publications and helpful links

General Publications

• Ghosh S, Gensler LS, Yang Z, Gasink C, Chakravarty SD, Farahi K, Ramachandran P, Ott E, Strober BE. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs. Drug Saf. 2019 Jun;42(6):751-768. doi: 10.1007/s40264-019-00797-3. Erratum In: Drug Saf. 2019 Apr 22;:
• Papp KA, Langley RG, Lebwohl M, Krueger GG, Szapary P, Yeilding N, Guzzo C, Hsu MC, Wang Y, Li S, Dooley LT, Reich K; PHOENIX 2 study investigators. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2). Lancet. 2008 May 17;371(9625):1675-84. doi: 10.1016/S0140-6736(08)60726-6.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: March 24, 2006
• First Submitted That Met QC Criteria: March 24, 2006
• First Posted (Estimate): March 28, 2006

Study Record Updates

• Last Update Posted (Estimate): January 24, 2013
• Last Update Submitted That Met QC Criteria: January 16, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Psoriasis; CNTO 1275; biologic; IL-12; ustekinumab; IL-23; interleukin-12; interleukin-23; CNTO1275; IL12; Moderate to Severe Plaque-Type Psoriasis; interleukin 23; IL23; interleukin 12
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR006325; C0743T09 (Other Identifier: Centocor R&D, USA); 2005-003530-17 (EudraCT Number)