Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris

Psoriasis Clinical Trial

— PAUSE  

Official title:

Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01999868
• Other study ID #: DAIT ITN059AI
• Status: Completed
• Phase: Phase 2
• Start date: March 19, 2014
• Est. completion date: March 1, 2018

Study information

• Verified date: December 2018
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if the use of ustekinumab, followed by abatacept, will prevent relapse in people with moderate to severe plaque psoriasis.

Description:

Psoriasis is a chronic immune disease of the skin and joints that affects about 2% of the population. The most common form of psoriasis is plaque psoriasis, also called psoriasis vulgaris. A variety of drugs, including biologics, are available for treatment of moderate to severe psoriasis. When biologic agents are stopped, psoriasis can return (relapse) and often requires the biologic to be restarted and continued. No treatment program has been identified to prevent relapse of psoriasis.

The study design has a lead-in period of weight-based ustekinumab treatment, with all participants receiving either 45 mg ustekinumab (<= 100 kg) or 90 mg ustekinumab (> 100 kg) administered subcutaneously at weeks 0 and 4. At week 12, participants will be assessed for a Psoriasis Area and Severity Index (PASI) 75 response to ustekinumab. Participants who do not achieve a PASI 75 score will be discontinued from the investigation and permitted to seek standard therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: March 1, 2018
• Est. primary completion date: December 7, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• A diagnosis of plaque psoriasis for at least 6 months

• Baseline Psoriasis Area and Severity Index (PASI) score >= 12

• >=10% body surface area psoriasis involvement

• Willingness to forgo other available psoriasis therapies, live vaccines, and pregnancy during the trial

• Ability and willingness to provide informed consent and comply with study requirements

Exclusion Criteria:

• Non-plaque forms of psoriasis

• Grade 2 or 3 moderate to severe psoriatic arthritis not adequately managed with non-steroidal anti-inflammatory drugs (NSAIDs)

• Myocardial infarction, unstable angina, cerebrovascular accident, or other significant cardiovascular event within the previous one year

• Chronic obstructive pulmonary disease (COPD)

• Comorbid condition that requires regular systemic corticosteroid treatment

• History of malignancy, except treated basal cell skin carcinoma

• Treated basal cell skin carcinoma within the previous 5 years

• Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease, or any other medical condition that, in the investigator's opinion, places the participant at risk by participating in this study

• History of recent or ongoing uncontrolled bacterial, viral, fungal, or other opportunistic infections

• Evidence of infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV)

• Positive QuantiFERON-TB Gold test. Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON-TB Gold test.

• Severe reaction or anaphylaxis to any human monoclonal antibody

• Any previous treatment with agents targeting Interleukin (IL)-12 or IL-23, including ustekinumab

• Any previous treatment with abatacept

• Treatment with biologic agents within previous 3 months, including adalimumab, etanercept, and infliximab

• Treatment with immunosuppressive medications, including methotrexate, cyclosporine, oral retinoids, prednisone, or phototherapy within previous 4 weeks

• Topical psoriasis treatment within previous 2 weeks, including topical corticosteroids, vitamin D analogues, retinoids, calcineurin inhibitors, salicylic acid, and coal tar

• Investigational study medication within previous 6 months

• Liver function test (aspartate aminotransferase [AST], alanine aminotransferase [ALT], or alkaline phosphatase) results that are >/= 2x the upper limit of normal (ULN).

• Serum creatinine >= 2x the ULN.

• Any of the following hematologic abnormalities, confirmed by repeat test at least 1 week apart:

1. White blood count <3,000/µL or >14,000/µL;

2. Lymphocyte count <1,000/µL;

3. Neutrophil count <1,500/µL;

4. Platelet count <150,000 /µL; or

5. Hemoglobin <10 g/dL.

• Females who are pregnant, lactating, planning on pregnancy during the study period, or unwilling to use FDA-approved method of birth control

• Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) in the 6 weeks before enrollment

• BCG (Bacillus Calmette-Guérin) vaccine one year prior to enrollment

Related Conditions & MeSH terms

• Psoriasis

Intervention

Biological:
• Ustekinumab
Ustekinumab interferes with the actions of proteins, interleukin 12 (IL12) and interleukin 23 (IL23), which reduces inflammation (swelling) in the skin. Stelara™ is the trade name for ustekinumab and is approved by the U.S. Food and Drug Administration (FDA) to treat psoriasis. Dose: Participants who weigh <= 100 kg at study entry will receive 45 mg of ustekinumab. Participants who weigh > 100 kg at study entry will receive 90 mg of ustekinumab.
• Abatacept
Abatacept (one form of the protein called CTLA4-Ig) interacts with the immune system, reducing the activity of T-cells and may prevent relapse. Orencia™ is the trade name for abatacept, and it is approved by the FDA to treat rheumatoid arthritis in adults. Dose: 125 mg sub-cutaneous injection

Drug:
• UST Placebo
The abatacept treatment group will also receive subcutaneous placebo for ustekinumab (sterile normal saline) at week 16 and week 28, corresponding to the ustekinumab dosing regimen.
• ABA Placebo
The ustekinumab treatment group will also receive weekly subcutaneous injections of placebo for abatacept from week 12 to week 39, corresponding to the abatacept dosing regimen.

Locations

Country	Name	City	State
Canada	Kirk Barber Research	Calgary	Alberta
Canada	Innovaderm Research Inc.	Montreal	Quebec
United States	University of Michigan	Ann Arbor	Michigan
United States	Northwestern University	Chicago	Illinois
United States	Case Western University	Cleveland	Ohio
United States	Dermatology Research Associates	Los Angeles	California
United States	Tulane University School of Medicine: Dept. of Dermatology	New Orleans	Louisiana
United States	The Rockefeller University	New York	New York
United States	The University of Utah	Salt Lake City	Utah
United States	Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Immune Tolerance Network (ITN)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)	The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of = 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is = Week 12 PASI + [(Baseline PASI -Week 12 PASI)/2]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).	Post-randomization (Week 12 to 88)
Secondary	Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)	The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of = 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were considered to have not experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).	Post-randomization (Week 12 to 88)
Secondary	Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)	The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of = 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI). Participants who terminated early due to reasons other than psoriasis relapse or worsening psoriasis were considered to have a missing relapse status at time of drop-out and were excluded from the analyses. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).	Post-randomization (Week 12 to 88)
Secondary	Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)	Time in weeks from Week 12 to psoriasis relapse. Psoriasis relapse is defined as loss of = 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is = Week 12 PASI + [(Baseline PASI -Week 12 PASI)/2]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).	Post-randomization (Week 12 to 88)
Secondary	Time to Psoriasis Relapse (Treating Drop-Outs as Censored)	Time in weeks from Week 12 to psoriasis relapse. Psoriasis relapse is defined as loss of = 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is = Week 12 PASI + [(Baseline PASI -Week 12 PASI)/2]). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were censored at the time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).	Post-randomization (Week 12 to 88)
Secondary	Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)	Percentage of participants who were classified as cleared or minimal in the Physician's Global Assessment (PGA) average score at the specified post-randomization time point. The PGA assesses the severity of the psoriasis in 3 components: induration, erythema and scaling. Each component is given a score ranging from 0 to 5 based on the majority of the participant's psoriasis lesions, with higher scores indicating worse disease. A PGA average score < 1.5 was classified as "cleared or minimal."	Week 40, Week 88
Secondary	Change in Dermatology Life Quality Index (DLQI)	Change in the Dermatology Life Quality Index (DLQI) score from Week 12 to the specified post-randomization time point. DLQI is a 10-question, participant-reported questionnaire that assesses quality of life with respect to skin conditions in the areas of symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Each question measures the level of effect that the skin condition has on quality of life, and responses range from 'Not at all' (score = 0) to 'Very much' (score = 3). The overall score is the sum of the scores for all 10 questions and ranges from 0-30, with higher scores indicating worse quality of life.	Week 40, Week 88
Secondary	Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase)	Number of participants who experienced adverse events (AEs) during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.	Lead-In Phase (Week 0 to 12)
Secondary	Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase)	Number of adverse events (AEs) that occurred during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.	Lead-In Phase (Week 0 to 12)
Secondary	Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization)	Number of participants who experienced adverse events (AEs) during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.	From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Secondary	Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization)	Number of adverse events (AEs) that occurred during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.	From randomization (Week 12) to last safety follow-up visit (up to Week 100)

External Links

•   Immune Tolerance Network (ITN) website
•   National Institute of Allergy and Infectious Diseases (NIAID) website
•   PAUSE (ITN059AI) ITN Study website