Clinical trial NCT02978690: Spesolimab (BI 655130) Single Dose in Generalized Pustular Psoriasis
Official title: Multi-centre, Open-label, Single Arm, Phase I Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacogenomics and Efficacy of a Single Intravenous Dose of Spesolimab in Patients With Active Generalized Pustular Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2016-12-01
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I, open label, single group study that is being performed to assess the safety, tolerability, Pharmacokinetics (PK) , Pharmacogenomics (PGx) and efficacy of a single dose of spesolimab in adult patients with active Generalized Pustular Psoriasis (GPP).


Eligibility criteria: Inclusion criteria:

* Male or female patients, aged 18 to 75 years at screening,
* A known and documented history of Generalized Pustular Psoriasis
* Presenting with a flare of Generalized Pustular Psoriasis
* A Generalized Pustular Psoriasis Physician Global Assessment score of at least moderate severity,
* Generalized Pustular Psoriasis patients receiving maintenance treatment with retinoids and/or methotrexate for at least 4 weeks or Generalized Pustular Psoriasis patients not receiving any maintenance therapy, at screening,
* Signed and dated written informed consent prior to admission to the study,
* Women of childbearing potential must be ready and able to use highly effective methods of birth control per 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.

Male patients must be ready and able to use condoms.

- Further inclusion criteria apply

Exclusion criteria:

* Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
* Immediate life-threatening flare of Generalized Pustular Psoriasis or requiring intensive care treatment, according, to the judgement of the investigator. Life-threatening complications mainly include, but are not limited to, cardiovascular/cytokine driven shock, pulmonary distress,
* Identified, ongoing serious/severe infection,
* Acute generalized exanthematous pustulosis (AEGP)
* Patient's clinical presentation being considered due to the differential diagnosis of toxic epidermal necrosis or Stevens-Johnson syndrome,
* Currently involved in or intending to participate in another investigational study during the course of this trial,
* Previous enrolment in this trial
* Use of any restricted medication, or any drug considered likely to interfere with the safe conduct of the study
* Background therapy with ciclosporin within the last 30 days preceding the second screening visit,
* Severe, progressive, or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof, as judged by the investigator.
* Known chronic or relevant acute infections including active tuberculosis, HIV or viral hepatitis; QuantiFERON® tuberculosis test will be performed at screening. 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.
* Patient with a transplanted organ (with exception of a corneal transplant \> 12 weeks prior to screening) or who have ever received stem cell therapy (e.g., Prochymal).

Known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.

* Any documented active or suspected malignancy or history of malignancy within 5 years prior to second screening visit, 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 Generalized Pustular Psoriasis, surgical procedure (i.e., organ transplant), medical examination finding (including vital signs and electrocardiogram), or laboratory value at the second 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,
* Further exclusion criteria apply

Primary outcomes:
measure: Percentage of Patients With Adverse Reactions, Defined as Drug-related Adverse Events (AE)
timeFrame: Up to 140 days from the administration of spesolimab.
Secondary outcomes:
measure: Percent Change From Baseline in Generalized Pustular Psoriasis Area and Severity Index (GPPASI) Total Score at Week 2
timeFrame: At baseline and at Week 2.
measure: Proportion of Patients With Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) Total Score of 0 (Clear) or 1 (Almost Clear) at Week 2
timeFrame: At Week 2.
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at Week 2
timeFrame: At baseline and at Week 2.
measure: Change From Baseline in Pain Visual Analog Scale (VAS) Score at Week 2
timeFrame: At baseline and at Week 2.
measure: Area Under the Concentration-time Curve of Spesolimab in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
timeFrame: Within 1.5 hours (h) before and 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 312 h, 480 h, 648 h, 1992 h, 3336 h after spesolimab administration.
measure: Maximum Measured Concentration of Spesolimab in Plasma (Cmax)
timeFrame: Within 1.5 hours (h) before and 0.5 h, 24 h, 48 h, 72 h, 96 h, 120 h, 144 h, 312 h, 480 h, 648 h, 1992 h, 3336 h after spesolimab administration.
Other outcomes:
Locations:
city: Paris
country: France
facility: HOP Saint-Louis
city: Aichi, Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National Univ. Hosp
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Tunisia
country: Tunisia
facility: Hedi Chaker Hospital, Department of Dermatology
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: