BI 655066 Dose Ranging in Psoriasis, Active Comparator Ustekinumab

A 48 Weeks Study of Three Different Dose Regimens of BI 655066 Administered Subcutaneously in Patients With Moderate to Severe Chronic Plaque Psoriasis (Randomised, Dose-ranging, Active-comparator-controlled (Ustekinumab), Double-blind Within Dose Groups of BI 655066)

The overall purpose of this trial is to assess clinical efficacy and safety of different subcutaneous doses of BI 655066 in adult patients with chronic plaque psoriasis in order to select doses for further clinical trials.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Ustekinumab; Drug: BI 655066; Drug: BI 655066; Drug: BI 655066

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Markham, Ontario, Canada
      • 1311.2.20002 Boehringer Ingelheim Investigational Site
    • Peterborough, Ontario, Canada
      • 1311.2.20005 Boehringer Ingelheim Investigational Site
    • Waterloo, Ontario, Canada
      • 1311.2.20003 Boehringer Ingelheim Investigational Site
  • Quebec
    • Sainte-Foy, Quebec, Canada
      • 1311.2.20004 Boehringer Ingelheim Investigational Site
• Finland
  • Helsinki, Finland
    • 1311.2.35802 Boehringer Ingelheim Investigational Site
  • Turku, Finland
    • 1311.2.35801 Boehringer Ingelheim Investigational Site
• France
  • Marseille, France
    • 1311.2.33005 Boehringer Ingelheim Investigational Site
  • Nice, France
    • 1311.2.33002 Boehringer Ingelheim Investigational Site
  • Paris, France
    • 1311.2.33001 Boehringer Ingelheim Investigational Site
  • Pessac, France
    • 1311.2.33004 Boehringer Ingelheim Investigational Site
  • Rouen, France
    • 1311.2.33003 Boehringer Ingelheim Investigational Site
  • Toulouse, France
    • 1311.2.33006 Boehringer Ingelheim Investigational Site
• Germany
  • Berlin, Germany
    • 1311.2.49001 Boehringer Ingelheim Investigational Site
  • Dresden, Germany
    • 1311.2.49003 Boehringer Ingelheim Investigational Site
  • Lübeck, Germany
    • 1311.2.49005 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1311.2.49002 Boehringer Ingelheim Investigational Site
  • Münster, Germany
    • 1311.2.49004 Boehringer Ingelheim Investigational Site
• Norway
  • Oslo, Norway
    • 1311.2.47001 Boehringer Ingelheim Investigational Site
  • Ålesund, Norway
    • 1311.2.47002 Boehringer Ingelheim Investigational Site
• Sweden
  • Stockholm, Sweden
    • 1311.2.46001 Boehringer Ingelheim Investigational Site
• United States
  • California
    • Los Angeles, California, United States
      • 1311.2.10010 Boehringer Ingelheim Investigational Site
  • Florida
    • Port Orange, Florida, United States
      • 1311.2.10013 Boehringer Ingelheim Investigational Site
  • Illinois
    • Arlington Hts, Illinois, United States
      • 1311.2.10003 Boehringer Ingelheim Investigational Site
  • Michigan
    • Bay City, Michigan, United States
      • 1311.2.10002 Boehringer Ingelheim Investigational Site
  • Minnesota
    • Fridley, Minnesota, United States
      • 1311.2.10004 Boehringer Ingelheim Investigational Site
  • New Jersey
    • East Windsor, New Jersey, United States
      • 1311.2.10001 Boehringer Ingelheim Investigational Site
    • Verona, New Jersey, United States
      • 1311.2.10009 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States
      • 1311.2.10007 Boehringer Ingelheim Investigational Site
  • Oregon
    • Portland, Oregon, United States
      • 1311.2.10005 Boehringer Ingelheim Investigational Site
  • Texas
    • Dallas, Texas, United States
      • 1311.2.10006 Boehringer Ingelheim Investigational Site
    • Houston, Texas, United States
      • 1311.2.10011 Boehringer Ingelheim Investigational Site
  • Washington
    • Spokane, Washington, United States
      • 1311.2.10012 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Body Mass Index (BMI) >/= 18.5 and < 40 kg/m²
• Patients with stable moderate to severe chronic plaque-type psoriasis with or without psoriatic arthritis involving >/= 10% body surface area, with disease severity PASI >/= 12 and sPGA score of moderate and above (score of at least 3) at screening visit and visit 2 (randomisation), as assessed by the investigator
• Psoriasis disease duration of at least 6 months prior to screening, as assessed by the investigator
• Patients must be candidates for systemic psoriasis treatment or phototherapy, as assessed by the investigator
• Patients must be suitable candidates for ustekinumab (Stelara®) therapy as given in the local labelling
• Patient must give informed consent and sign an approved consent form prior to any study procedures in accordance with GCP and local legislation

Exclusion criteria:

• Patients with guttate, erythrodermic, or pustular psoriasis and patients with drug-induced psoriasis, as diagnosed by the investigator
• Evidence of current or previous clinically significant disease, medical condition other than psoriasis, or finding of the medical examination (including vital signs and ECG), that in the opinion of the investigator, would compromise the safety of the patient or the quality of the data. This criterion provides an opportunity for the investigator to exclude patients based on clinical judgment, even if other eligibility criteria are satisfied. (Psoriatic arthritis is not considered an exclusion criterion)
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders, or history of orthostatic hypotension, fainting spells or blackouts, that in the investigator's judgement, could jeopardize the safe conduct of the study.
• Clinically important acute or chronic infections including hepatitis and HIV.

With regards to tuberculosis the following applies:

Have signs or symptoms suggestive of current active or latent TB upon medical history, physical examination and/or a chest radiograph (both posterior-anterior and lateral views, taken within 3 months prior to the first administration of study drug and read by a qualified radiologist).

Have history of latent or active TB prior to screening, except for patients who have documentation of having completed an adequate treatment regimen at least 6 months prior to the first administration of study agent.

Have positive IGRA testing (QuantiFERON-TB Gold) within 2 months prior to or during screening, in which active TB has not been ruled out, except for patients with history of latent TB and documentation of having completed an adequate treatment regimen at least 6 months prior to the first administration of study agent.

• Have had a live vaccination </= 12 weeks prior to randomisation (visit 2). Patients must agree not to receive a live vaccination during the study. No BCG vaccines should be given for one year prior to randomisation (visit 2), during the study and for one year after last administration of study drug (according to the Stelara® SPC).
• History of clinically significant hypersensitivity to a systemically administered biologic agent or its excipients
• History of malignancy in the past 5 years or suspicion of active malignant disease except treated cutaneous squamous cell or basal cell carcinoma
• Has received any therapeutic agent directly targeted to IL-12, IL-23 (including ustekinumab (Stelara®))
• Use of biologic agents within 12 weeks (infliximab, etanercept, adalimumab, other biologics) prior to treatment, systemic anti-psoriatic medications or phototherapy within 4 weeks prior to treatment, or topical anti-psoriasis medications within 2 weeks prior to treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; BI 655066 s.c.	Drug: BI 655066; Medium dose; Drug: BI 655066; High dose; Drug: BI 655066; Low dose
Experimental: Arm 2; BI 655066 s.c.	Drug: BI 655066; Medium dose; Drug: BI 655066; High dose; Drug: BI 655066; Low dose
Experimental: Arm 3; BI 655066 s.c.	Drug: BI 655066; Medium dose; Drug: BI 655066; High dose; Drug: BI 655066; Low dose
Active Comparator: Arm 4; Ustekinumab s.c.	Drug: Ustekinumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12	Percentage of participants who achieved ≥90% reduction from baseline in Psoriasis Area and Severity Index score (PASI90) at Week 12. PASI score ranges from 0 (best) to 72 (worst).	Baseline and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24	Percentage of participants who achieved ≥75% reduction from baseline in Psoriasis Area and Severity Index score (PASI75) at Weeks 12 and 24. PASI score ranges from 0 (best) to 72 (worst).	Baseline, Week 12 and Week 24
Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12	Percentage of participants who achieved 100% reduction from baseline in Psoriasis Area and Severity Index score (PASI100) at Week 12. PASI score ranges from 0 (best) to 72 (worst).	Baseline and Week 12
Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12	Percentage of participants who achieved ≥50% reduction from baseline in Psoriasis Area and Severity Index score (PASI50) at Week 12. PASI score ranges from 0 (best) to 72 (worst).	Baseline and Week 12
Achievement of PASI90 at Week 24	Percentage of participants who achieved PASI90 at Week 24. PASI score ranges from 0 (best) to 72 (worst).	Week 24
Percentage Change in PASI Score From Baseline at Week 12	Percentage change in Psoriasis Area and Severity Index (PASI) from baseline at Week 12. PASI score ranges from 0 (best) to 72 (worst).	Baseline and Week 12
Achievement of sPGA Clear or Almost Clear at Week 12	Percentage of participants who achieved static Physician Global Assessment (sPGA) clear or almost clear at Week 12. sPGA is assessed on a six-point scale from 0 (clear) to 5 (severe).	Week 12
Time to Loss of PASI50 Response	Time to loss of PASI50 response.	From first drug administration until end of follow-up period, up to 48 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Suleiman AA, Minocha M, Khatri A, Pang Y, Othman AA. Population Pharmacokinetics of Risankizumab in Healthy Volunteers and Subjects with Moderate to Severe Plaque Psoriasis: Integrated Analyses of Phase I-III Clinical Trials. Clin Pharmacokinet. 2019 Oct;58(10):1309-1321. doi: 10.1007/s40262-019-00759-z.
• Suleiman AA, Khatri A, Oberoi RK, Othman AA. Exposure-Response Relationships for the Efficacy and Safety of Risankizumab in Japanese Subjects with Psoriasis. Clin Pharmacokinet. 2020 May;59(5):575-589. doi: 10.1007/s40262-019-00829-2.
• Papp KA, Blauvelt A, Bukhalo M, Gooderham M, Krueger JG, Lacour JP, Menter A, Philipp S, Sofen H, Tyring S, Berner BR, Visvanathan S, Pamulapati C, Bennett N, Flack M, Scholl P, Padula SJ. Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2017 Apr 20;376(16):1551-1560. doi: 10.1056/NEJMoa1607017.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: February 3, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: July 29, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Immunologic Factors; Dermatologic Agents; Antibodies, Monoclonal; Ustekinumab
• Other Study ID Numbers: 1311.2 (Other Grant/Funding Number: Boehringer Ingelhem); 2012-004384-48 (EudraCT Number: EudraCT)