BI 655066 Versus Placebo & Active Comparator (Ustekinumab) in Patients With Moderate to Severe Chronic Plaque Psoriasis

Psoriasis Clinical Trial

Official title:

BI 655066 Versus Ustekinumab and Placebo Comparators in a Randomized Double Blind trIal for Maintenance Use in Moderate to Severe Plaque Type Psoriasis-2 (UltIMMa-2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02684357
• Other study ID #: M15-995
• Secondary ID: 2015-003622-1313
• Status: Completed
• Phase: Phase 3
• Start date: March 2016
• Est. completion date: September 2017

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized double blind, double dummy, placebo and active comparator controlled, parallel design study that is being performed to assess the safety and efficacy of risankizumab (BI 655066) to support registration for the treatment of moderate to severe chronic plaque psoriasis in adult patients.

Description:

Participants were randomized to receive either placebo, ustekinumab, or risankizumab in Part A. All participants received 2 sets of injections to maintain the blind: the placebo arm received placebo for risankizumab and placebo for ustekinumab), the risankizumab arm received risankizumab and placebo for ustekinumab, and the ustekinumab arm received ustekinumab and placebo for risankizumab. Participants who received placebo in Part A switched to risankizumab in Part B; participants who received ustekinumab or risankizumab in Part A continued to receive the same treatment (ustekinumab or risankizumab) in Part B.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 577
• Est. completion date: September 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Male or female patients. Women of childbearing potential* must be ready and able to use highly effective methods of birth control per International Council on Harmonisation (ICH) M3(R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.

*Women of childbearing potential are defined as:

• having experienced menarche and are

• not postmenopausal (12 months with no menses without an alternative medical cause) and are

• not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

• Age = 18 years at screening

• Have a diagnosis of chronic plaque psoriasis (with or without psoriatic arthritis) for at least 6 months before the first administration of study drug.Duration of diagnosis may be reported by the patient,

• Have stable moderate to severe chronic plaque psoriasis with or without psoriatic arthritis at both Screening and Baseline (Randomization):

1. Have an involved body surface area (BSA) = 10% and

2. Have a Psoriasis Area and Severity Index (PASI) score = 12 and

3. Have a static Physician Global Assessment (sPGA) score of = 3.

• Must be candidates for systemic therapy or phototherapy for psoriasis treatment, as assessed by the investigator

• Must be a candidate for treatment with Stelara® (ustekinumab) according to local label.

• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practices (GCP) and local legislation

Exclusion criteria:

• Patients with:

1. non-plaque forms of psoriasis (including guttate, erythrodermic, or pustular),

2. current drug-induced psoriasis (including an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium),

3. active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis that might confound trial evaluations according to investigator's judgment,

• Previous exposure to BI 655066,

• Currently enrolled in another investigational study or less than 30 days (from screening) since completing another investigational study (participation in observational studies is permitted),

• Previous exposure to ustekinumab (Stelara®),

• Use of any restricted medication, or any drug considered likely to interfere with the safe conduct of the study,

• Major surgery performed within 12 weeks prior to randomization or planned within 12 months after screening (e.g., hip replacement, aneurysm removal, stomach ligation),

• Known chronic or relevant acute infections including active tuberculosis, HIV or viral hepatitis; QuantiFERON® tuberculosis (TB) test or purified protein derivative (PPD) skin test will be performed according to local labelling for comparator products. If the result is positive, patients may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment should have been initiated and maintained according to local country guidelines,

• Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix,

• Evidence of a current or previous disease, medical condition (including chronic alcohol or drug abuse) other than psoriasis, surgical procedure (i.e., organ transplant), medical examination finding (including vital signs and electrocardiogram [ECG]), or laboratory value at the screening visit outside the reference range that is in the opinion of the investigator, is clinically significant and would make the study participant unreliable to adhere to the protocol or to complete the trial, compromise the safety of the patient, or compromise the quality of the data,

• History of allergy/hypersensitivity to a systemically administered biologic agent or its excipients,

• Women who is pregnant, nursing, or who plans to become pregnant while in the trial,

• Previous enrolment in this trial.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• risankizumab
Risankizumab pre-filled syringe, administered by subcutaneous (SC) injection
• ustekinumab
Ustekinumab pre-filled syringe, administered by subcutaneous (SC) injection
• placebo for risankizumab
Placebo for risankizumab pre-filled syringe, administered by subcutaneous (SC) injection
• placebo for ustekinumab
Placebo for ustekinumab pre-filled syringe, administered by subcutaneous (SC) injection

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie	Boehringer Ingelheim

References & Publications (1)

Sonenshein GE, Siekevitz M, Siebert GR, Gefter ML. Control of immunoglobulin secretion in the murine plasmacytoma line MOPC 315. J Exp Med. 1978 Jul 1;148(1):301-12. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving 90% Improvement in Psoriasis Area and Severity Index (PASI) Score (PASI90) at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. Non-responder imputation (NRI) was used for missing data.	Week 16
Primary	Percentage of Participants Achieving a Static Physician Global Assessment (sPGA) Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI100 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 0 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired. A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving a Psoriasis Symptom Scale (PSS) Score of 0 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving PASI90 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving PASI100 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI00 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving sPGA Score of Clear at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving PASI90 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI90 is defined as at least a 90% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 52
Secondary	Percentage of Participants Achieving PASI100 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI00 is defined as a 100% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 52
Secondary	Percentage of Participants Achieving sPGA Score of Clear at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 52
Secondary	Percentage of Participants Achieving PASI75 at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 12
Secondary	Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 12 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 12
Secondary	Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 16 in Participants Who Received Risankizumab Compared With Ustekinumab (Part A)	DLQI is a 10-question questionnaire that asks the participant to evaluate the degree that psoriasis has affected their quality of life in the last week and includes 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment). Responses to each domain are not relevant (0), not at all (0), a little (1), a lot (2), and very much (3). The DLQI is calculated by summing the scores of the questions and ranges from 0 to 30, where 0-1 = no effect on patient's life, 2-5 = small effect, 6-10 = moderate effect, 11-20 = very large effect, and 21-30 = extremely large effect on patient's life. The higher the score, the more the quality of life is impaired. A 5-point change from baseline is considered a clinically important difference. NRI was used for missing data.	Week 16
Secondary	Change From Baseline to Week 16 in PSS Total Score in Participants Who Received Risankizumab Compared With Placebo (Part A)	The PSS asks the participant to rate the severity of symptoms of psoriasis in the last 24 hours (pain, redness, itching, and burning) using a 5-point Likert -type scale ranging from 0 (none) to 4 (very severe). The PSS is calculated by summing the scores of the questions and ranges from 0 to 16, where the higher the score, the greater the severity of psoriasis symptoms. A negative change in PSS total score indicates improvement. Last observation carried forward (LOCF) imputation was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving PASI75 at Week 16 in Participants Who Received Risankizumab Compared With Placebo (Part A)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 16
Secondary	Percentage of Participants Achieving sPGA Score of Clear or Almost Clear at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)	The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA ranges from 0 to 4, and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean >0, <1.5; Mild (2) = mean =1.5, <2.5; Moderate (3) = mean =2.5, <3.5; and Severe (4) = mean =3.5. NRI was used for missing data.	Week 52
Secondary	Percentage of Participants Achieving PASI75 at Week 52 in Participants Who Received Risankizumab Compared With Ustekinumab (Part B)	PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The severity of each sign was assessed using a 5-point scale, where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. The PASI score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. PASI75 is defined as at least a 75% reduction in PASI score compared with the Baseline PASI score. The percent reduction in score is calculated as (PASI score at Baseline - score at follow-up visit) / PASI score at Baseline * 100. NRI was used for missing data.	Week 52

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