Clinical trial NCT04399837: A Study to Test Whether BI 655130 (Spesolimab) Prevents Flare-ups in Patients With Generalized Pustular Psoriasis
Official title: Effisayil™ 2: Multi-center, Randomized, Parallel Group, Double Blind, Placebo Controlled, Phase IIb Dose-finding Study to Evaluate Efficacy and Safety of BI 655130 (Spesolimab) Compared to Placebo in Preventing Generalized Pustular Psoriasis (GPP) Flares in Patients With History of GPP.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Generalized Pustular Psoriasis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2020-05-22
Enrollment: 123
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a study in adolescents and adults with Generalized Pustular Psoriasis (GPP). People between 12 and 75 years old can take part in the study. The study is open to people who had GPP flare-ups in the past but whose skin is clear or almost clear when they join the study. The purpose of the study is to test 3 different doses of a medicine called spesolimab and to see whether it helps to prevent GPP flare-ups.

Participants are put into 4 groups by chance. Three groups get different doses of spesolimab. The fourth group gets a placebo. Placebo looks like spesolimab but does not contain any medicine.

Spesolimab and placebo are given as an injection under the skin. Participants are in the study for about 1 year and 4 months. During this time, they visit the study site about 15 times. For the first 11 months, participants get spesolimab or placebo injections every month. At the study visits, the doctors check participants' skin for signs of a new GPP flare-up. The doctors also check the general health of the participants.

If a participant has a GPP flare-up during the study, more visits may be necessary. In case of a flare-up, participants get a dose of spesolimab as an infusion into a vein.


Eligibility criteria: Inclusion Criteria:

* Patients with a known and documented history of GPP per ERASPEN criteria (see Section 3.3.1) regardless of IL36RN mutation status, with at least 2 presentations of moderate to severe GPP flares with fresh pustulation (new appearance or worsening) in the past.
* Patients with a GPPGA score of 0 or 1 at screening and randomization.
* Patients who are not on concomitant GPP treatment at time of randomization (V2) must have had at least two presentations of moderate to severe GPP flare in the past year, at least one of which had evidence of either fever and/or elevated CRP and/or elevated WBC, and/or asthenia and/or myalgia.
* Patients who are not on concomitant GPP treatment at time of randomization (V2) but who were on concomitant GPP treatment until shortly before randomization (V2) (≤ 12 weeks before randomization), these patients must have a history of flaring while on concomitant treatment for GPP or in case of dose reduction or discontinuation of their concomitant medication.
* Patients who are on concomitant treatment regimen with retinoids and/or methotrexate and/or cyclosporine must stop at the day of randomization (V2). These patients must have a history of flaring while on concomitant treatment for GPP or in case of dose reduction or discontinuation of these concomitant medications.
* Male or female patients, aged 12 to 75 years at screening. For all patients, a minimum weight of 40 kg is required.
* Signed and dated written informed consent and assent in accordance with ICH-GCP and local legislation prior to admission in the trial.
* Women of childbearing potential (WOCBP)1 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 CTP as well as in the patient, parent(s) (or patient's legal guardian) information.

Exclusion Criteria:

1. Patients with SAPHO (Synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome.
2. Patients with primary erythrodermic psoriasis vulgaris.
3. Severe, progressive, or uncontrolled hepatic disease, defined as \>3-fold Upper Limit of Normal (ULN) elevation in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) or alkaline phosphatase, or \>2-fold ULN elevation in total bilirubin.
4. Treatment with:

   1. Any restricted medication as specified in the CTP, or any drug considered likely to interfere with the safe conduct of the study, as assessed by the investigator.
   2. Any prior exposure to BI 655130 or another IL36R inhibitor biologic.
5. Increased risk of infectious complications (e.g. recent pyogenic infection, any congenital or acquired immunodeficiency (e.g. HIV), past organ or stem cell transplantation), as assessed by the investigator.
6. Relevant chronic or acute infections including active tuberculosis, human immunodeficiency virus (HIV) infection or viral hepatitis at the time of randomization. A patient can be re-screened if the patient was treated and is cured from the acute infection.
7. Active or Latent Tuberculosis (TB):

   * Patients with active tuberculosis should be excluded
   * Patients with a positive QuantiFERON® (or if applicable, T-Spot®) TB test during screening are excluded, unless the patient had previous diagnosis of active or latent TB and has completed appropriate treatment per the discretion of the local investigator within the last 3 years and at the latest at the time of screening (i.e. 2 to 4 weeks before study drug administration); patients may be re-screened once to meet this criterion)
   * Patients with suspected false positive or indeterminate QuantiFERON® (or if applicable, T-Spot®) TB result may be re-tested once
   * If QuantiFERON® (or if applicable, T-Spot®) TB testing is not available or provides indeterminate results after repeat testing, a tuberculin skin test (TST) can be performed: A TST reaction of ≥10mm (≥5mm if receiving ≥15mg/d prednisone or its equivalent) is considered positive.
8. History of allergy/hypersensitivity to the systemically administered trial medication agent or its excipients.

Further exclusion criteria apply.

Primary outcomes:
measure: Time to First Generalized Pustular Psoriasis (GPP) Flare
timeFrame: GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.
Secondary outcomes:
measure: Key Secondary Endpoint: The Occurrence of at Least One Generalized Pustular Psoriasis (GPP) Flare up to Week 48
timeFrame: GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.
measure: Time to First Worsening of Psoriasis Symptom Scale (PSS) up to Week 48
timeFrame: PSS assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Visit window was ±7 days.
measure: Time to First Worsening of Dermatology Quality of Life Index (DLQI) up to Week 48
timeFrame: DLQI assessments were performed at: Baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 24, 36 and 48). Visit window was ±7 days. Time window for Week 48 was from Week 46 to Week 50.
measure: Sustained Remission
timeFrame: GPPGA was regularly assessed at baseline (Week 1) and up to Week 48 (at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48). Patients could come to site for flare confirmation anytime as unscheduled visit. Visit window was ±7 days.
measure: The Occurrence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 62 weeks (for detailed timeframe see description).
Other outcomes:
Locations:
city: Auburn Hills
country: United States
facility: Oakland Hills Dermatology
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Caba
country: Argentina
facility: Buenos Aires Skin S.A.
city: Caba
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Vitacura
country: Chile
facility: Clínica Dermacross S.A.
city: Guangzhou
country: China
facility: Sun yet-sen Memorial Hospital, Sun yet-sen Univesity
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Shanghai
country: China
facility: Shanghai Skin Disease Hospital
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Tianjin
country: China
facility: Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital
city: Xi'an
country: China
facility: Second Affiliated Hospital of Xi'an JiaoTong University
city: Nice
country: France
facility: HOP l'Archet
city: Paris
country: France
facility: HOP Saint-Louis
city: Bad Bentheim
country: Germany
facility: Fachklinik Bad Bentheim
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn AöR
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: München
country: Germany
facility: Klinikum der Universität München - Campus Innenstadt
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Oldenburg
country: Germany
facility: Klinikum Oldenburg AöR
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg AÖR
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "Ippokrateio"
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
city: Aichi, Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Fukuoka, Kitakyushu
country: Japan
facility: Kyushu Rosai Hospital
city: Ibaraki, Inashiki-gun
country: Japan
facility: Tokyo Medical University Ibaraki Medical Center
city: Saitama, Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Tokyo, Hachioji
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
city: Tokyo, Shinjuku-ku
country: Japan
facility: Tokyo Medical University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National Univ. Hosp
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Johor Bahru
country: Malaysia
facility: Hospital Sultanah Aminah
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
city: Kota Kinabalu
country: Malaysia
facility: Queen Elizabeth Hospital
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuching, Sarawak
country: Malaysia
facility: Sarawak General Hospital
city: Muar
country: Malaysia
facility: Hospital Pakar Sultanah Fatimah
city: Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Guadalajara
country: Mexico
facility: Centro de Investigación de Enfermedades Autoinmunes S.C.
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Davao City
country: Philippines
facility: Southern Philippines Medical Center
city: Iloilo City, Iloilo
country: Philippines
facility: Iloilo Doctors Hospital
city: Makati City
country: Philippines
facility: Center for Skin Research, Testing and Product Development
city: Chelyabinsk
country: Russian Federation
facility: SBHI Chelyabinsk Reg.Clin.Derma.Dispen.
city: Kazan
country: Russian Federation
facility: LLC "Medical Center Azbuka Zdorovia"
city: Kirov
country: Russian Federation
facility: FSBEI HE "Kirov State Medical University"
city: Saint-Petersburg
country: Russian Federation
facility: 1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.
city: Saratov
country: Russian Federation
facility: Saratov State Med.Univ.n.a.Razumovskogo
city: St. Petersburg
country: Russian Federation
facility: LLC Skin Disease Clinic of Pier Volkenstein, St. Petersburg
city: St. Petersburg
country: Russian Federation
facility: LLC "Avrora Medfort"
city: Cape Town
country: South Africa
facility: Arthritis Clinical Research Trials
city: Esplugues Del Llobregat
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Linkou
country: Taiwan
facility: Chang Gung Medical Foundation (CGMF) - Linkou Bran
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Bangkok
country: Thailand
facility: Institute of Dermatology
city: Ratchatewi, Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Sfax
country: Tunisia
facility: Hedi Chaker Hospital, Department of Dermatology
city: Sousse
country: Tunisia
facility: Farhat Hached Hospital
city: Tunis
country: Tunisia
facility: La Rabta Hospital
city: Tunis
country: Tunisia
facility: Charles Nicolle Hospital
city: Tunis
country: Tunisia
facility: Habib Thameur Hospital
city: Bursa
country: Turkey
facility: Uludag University Medicine Faculty Departmant of Dermatology
city: Istanbul
country: Turkey
facility: Bezmi Alem Valide Sultan Vakif Gureba Egitim ve Arastirma Hastanesi
city: Istanbul
country: Turkey
facility: Istanbul Universitesi Cerrahpasa Tip Fakultesi
city: Istanbul
country: Turkey
facility: Marmara Universitesi Tip Fakultesi
city: Ha Noi
country: Vietnam
facility: National Hospital of Dermatology and Venereology
city: Ho Chi Minh
country: Vietnam
facility: HCMC Hospital of Dermato-Venereology
Study officials:
References:
citation: Morita A, Choon SE, Bachelez H, Anadkat MJ, Marrakchi S, Zheng M, Tsai TF, Turki H, Hua H, Rajeswari S, Thoma C, Burden AD. Design of Effisayil 2: A Randomized, Double-Blind, Placebo-Controlled Study of Spesolimab in Preventing Flares in Patients with Generalized Pustular Psoriasis. Dermatol Ther (Heidelb). 2023 Jan;13(1):347-359. doi: 10.1007/s13555-022-00835-6. Epub 2022 Nov 5.