Psoriasis
Conditions
Brief summary
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.
Interventions
DRUGBI 655066
Medium dose
DRUGUstekinumab
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | Baseline and 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | Baseline and 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). |
| Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | Baseline and 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). |
| Achievement of PASI90 at Week 24 | Week 24 | Percentage of participants who achieved PASI90 at Week 24. PASI score ranges from 0 (best) to 72 (worst). |
| Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Baseline, Week 12 and Week 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). |
| Achievement of sPGA Clear or Almost Clear at Week 12 | 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). |
| Time to Loss of PASI50 Response | From first drug administration until end of follow-up period, up to 48 weeks | Time to loss of PASI50 response. |
| Percentage Change in PASI Score From Baseline at Week 12 | Baseline and 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). |
Countries
Canada, Finland, France, Germany, Norway, Sweden, United States
Participant flow
Pre-assignment details
Participant flow shows disposition at the end of treatment.
Participants by arm
| Arm | Count |
|---|---|
| BI 655066 18 mg 18 mg BI 655066 administered by subcutaneous injection plus two placebo matching BI 655066 injections at Week 0, followed by two placebo matching BI 655066 injections each at Weeks 4 and 16. | 43 |
| BI 655066 90 mg 90 mg BI 655066 administered by subcutaneous injection plus two placebo matching BI 655066 injections at Week 0, followed 90mg BI 655066 plus one placebo matching BI 655066 injection at Weeks 4 and 16. | 41 |
| BI 655066 180 mg 180 mg BI 655066 administered by subcutaneous injection as two injections plus a placebo matching BI 655066 injection at Week 0, followed 180 mg BI 655066 administered as two injections at Weeks 4 and 16. | 42 |
| Stelara Stelara administered by subcutaneous injection plus two saline injections at Week 0, Stelara injection plus one saline injection at Weeks 4 and 16. Stelara dose was 45 mg for patients with body weight ≤100 kg at randomisation or 90 mg for patients with body weight \>100 kg at randomisation. | 40 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Other reason | 2 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | BI 655066 18 mg | BI 655066 90 mg | BI 655066 180 mg | Stelara | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.1 Years STANDARD_DEVIATION 14.2 | 49.3 Years STANDARD_DEVIATION 13.3 | 44.9 Years STANDARD_DEVIATION 14 | 45.4 Years STANDARD_DEVIATION 12.1 | 45.9 Years STANDARD_DEVIATION 13.5 |
| Sex: Female, Male Female | 20 Participants | 11 Participants | 13 Participants | 13 Participants | 57 Participants |
| Sex: Female, Male Male | 23 Participants | 30 Participants | 29 Participants | 27 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 43 | 22 / 41 | 20 / 42 | 17 / 40 |
| serious Total, serious adverse events | 5 / 43 | 6 / 41 | 0 / 42 | 3 / 40 |
Outcome results
Primary
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).
Time frame: Baseline and Week 12
Population: Full Analysis Set (FAS) which included all randomised patients who received at least 1 dose of trial medication and was based on the randomised treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655066 18 mg | Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | 32.6 Percentage of participants |
| BI 655066 90 mg | Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | 73.2 Percentage of participants |
| BI 655066 180 mg | Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | 81.0 Percentage of participants |
| BI 655066 90+180 mg | Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | 77.1 Percentage of participants |
| Stelara | Achievement of ≥90% Reduction From Baseline PASI Score (PASI90) at Week 12 | 40.0 Percentage of participants |
p-value: <0.000195% CI: [19, 53.8]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline and Week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655066 18 mg | Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | 14.0 Percentage of participants |
| BI 655066 90 mg | Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | 41.5 Percentage of participants |
| BI 655066 180 mg | Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | 50.0 Percentage of participants |
| BI 655066 90+180 mg | Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | 45.8 Percentage of participants |
| Stelara | Achievement of 100% Reduction From Baseline in PASI Score (PASI100) at Week 12 | 17.5 Percentage of participants |
p-value: 0.000895% CI: [11.3, 42.9]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline and Week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655066 18 mg | Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | 93.0 Percentage of participants |
| BI 655066 90 mg | Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | 100.0 Percentage of participants |
| BI 655066 180 mg | Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | 95.2 Percentage of participants |
| BI 655066 90+180 mg | Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | 97.6 Percentage of participants |
| Stelara | Achievement of ≥50% Reduction From Baseline in PASI Score (PASI50) at Week 12 | 87.5 Percentage of participants |
p-value: 0.070695% CI: [-0.8, 21.1]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline, Week 12 and Week 24
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BI 655066 18 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 24 | 55.8 Percentage of participants |
| BI 655066 18 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 12 | 67.4 Percentage of participants |
| BI 655066 90 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 24 | 92.7 Percentage of participants |
| BI 655066 90 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 12 | 97.6 Percentage of participants |
| BI 655066 180 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 12 | 90.5 Percentage of participants |
| BI 655066 180 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 24 | 92.9 Percentage of participants |
| BI 655066 90+180 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 12 | 94.0 Percentage of participants |
| BI 655066 90+180 mg | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 24 | 92.8 Percentage of participants |
| Stelara | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 12 | 77.5 Percentage of participants |
| Stelara | Achievement of ≥75% Reduction From Baseline in PASI Score (PASI75) at Weeks 12 and 24 | Week 24 | 70.0 Percentage of participants |
Comparison: Week 12p-value: 0.035595% CI: [1, 28.2]Cochran-Mantel-Haenszel
Comparison: Week 24p-value: 0.006295% CI: [6, 36.2]Cochran-Mantel-Haenszel
Secondary
Achievement of PASI90 at Week 24
Percentage of participants who achieved PASI90 at Week 24. PASI score ranges from 0 (best) to 72 (worst).
Time frame: Week 24
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655066 18 mg | Achievement of PASI90 at Week 24 | 30.2 Percentage of participants |
| BI 655066 90 mg | Achievement of PASI90 at Week 24 | 65.9 Percentage of participants |
| BI 655066 180 mg | Achievement of PASI90 at Week 24 | 85.7 Percentage of participants |
| BI 655066 90+180 mg | Achievement of PASI90 at Week 24 | 75.9 Percentage of participants |
| Stelara | Achievement of PASI90 at Week 24 | 55.0 Percentage of participants |
p-value: 0.0395% CI: [1.9, 37.7]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Week 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BI 655066 18 mg | Achievement of sPGA Clear or Almost Clear at Week 12 | 62.8 Percentage of participants |
| BI 655066 90 mg | Achievement of sPGA Clear or Almost Clear at Week 12 | 90.2 Percentage of participants |
| BI 655066 180 mg | Achievement of sPGA Clear or Almost Clear at Week 12 | 90.5 Percentage of participants |
| BI 655066 90+180 mg | Achievement of sPGA Clear or Almost Clear at Week 12 | 90.4 Percentage of participants |
| Stelara | Achievement of sPGA Clear or Almost Clear at Week 12 | 67.5 Percentage of participants |
p-value: 0.007295% CI: [5.7, 36.6]Cochran-Mantel-Haenszel
Secondary
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).
Time frame: Baseline and Week 12
Population: FAS including patients with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 655066 18 mg | Percentage Change in PASI Score From Baseline at Week 12 | -79.7 Percentage of PASI score | Standard Deviation 19.5 |
| BI 655066 90 mg | Percentage Change in PASI Score From Baseline at Week 12 | -93.4 Percentage of PASI score | Standard Deviation 7.7 |
| BI 655066 180 mg | Percentage Change in PASI Score From Baseline at Week 12 | -90.7 Percentage of PASI score | Standard Deviation 23.1 |
| BI 655066 90+180 mg | Percentage Change in PASI Score From Baseline at Week 12 | -92.1 Percentage of PASI score | Standard Deviation 17.1 |
| Stelara | Percentage Change in PASI Score From Baseline at Week 12 | -82.1 Percentage of PASI score | Standard Deviation 19.5 |
Secondary
Time to Loss of PASI50 Response
Time to loss of PASI50 response.
Time frame: From first drug administration until end of follow-up period, up to 48 weeks
Population: FAS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BI 655066 18 mg | Time to Loss of PASI50 Response | 253 Days |
| BI 655066 90 mg | Time to Loss of PASI50 Response | NA Days |
| BI 655066 180 mg | Time to Loss of PASI50 Response | NA Days |
| BI 655066 90+180 mg | Time to Loss of PASI50 Response | NA Days |
| Stelara | Time to Loss of PASI50 Response | 338 Days |
p-value: <0.000195% CI: [0.1, 0.4]Log Rank