NCT04399837

A Study to Test Whether BI 655130 (Spesolimab) Prevents Flare-ups in Patients With Generalized Pustular Psoriasis

Completed Phase 2 Results posted Last updated 20 October 2025

What this trial tests

Phase 2 trial testing Spesolimab in Generalized Pustular Psoriasis in 123 participants. Completed in 23 November 2022.

Timeline

4 June 2020

Primary endpoint
23 November 2022

23 November 2022

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	123
Start date	4 June 2020
Primary completion	23 November 2022
Estimated completion	23 November 2022
Sites	72 locations across Italy, Japan, Malaysia, Taiwan, Vietnam, South Korea, Philippines, Tunisia

Drugs / interventions tested

• Spesolimab (SPESOLIMAB) — full drug profile →
• Placebo

Conditions studied

• Generalized Pustular Psoriasis — all drugs for Generalized Pustular Psoriasis →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 12 to 75, any sex, with Generalized Pustular Psoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to First Generalized Pustular Psoriasis (GPP) Flare Primary · 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.

A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2) up to week 48. Use of rescue medication, or investigator-prescribed Standard of Care (SoC) for GPP worsening, was considered to represent a GPP flare onset. GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each subscor

Group	Value	95% CI
Placebo	37.3	4.0 – NA
Spesolimab SC Low Dose	NA	NA – NA
Spesolimab SC Medium Dose	NA	NA – NA
Spesolimab SC High Dose	NA	NA – NA

Key Secondary Endpoint: The Occurrence of at Least One Generalized Pustular Psoriasis (GPP) Flare up to Week 48 Secondary · 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.

Proportion of patients with at least one GPP flare up to Week 48 is reported. Proportions were rounded up to three decimal places. A GPP flare was defined as increase in Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score by ≥ 2 from baseline and the pustular component of GPPGA ≥ 2. Any use of rescue medication, or investigator-prescribed SoC for GPP worsening, prior to week 48 was considered to represent the onset of a GPP flare. Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) relied on the clinical assessment of GPP patient's skin presentation. The t

Group	Value	95% CI
Placebo	0.516	0.348 – 0.680
Spesolimab SC Low Dose	0.226	0.114 – 0.398
Spesolimab SC Medium Dose	0.297	0.181 – 0.445
Spesolimab SC High Dose	0.127	0.050 – 0.289

Time to First Worsening of Psoriasis Symptom Scale (PSS) up to Week 48 Secondary · 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.

Worsening of Psoriasis Symptom Scale (PSS) was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The PSS is a 4-item patient-reported outcome (PRO) instrument that was developed to assess the severity of 4 psoriasis symptoms in patients with moderate to severe psoriasis. The symptoms included are: pain, redness, itching, and burning. Current symptom severity is assessed using a 5-point scale ranging from 0 (none) to 4 (very severe). The symptom scores are added to

Group	Value	95% CI
Placebo	16.0	4.0 – NA
Spesolimab SC Low Dose	NA	8.1 – NA
Spesolimab SC Medium Dose	NA	8.7 – NA
Spesolimab SC High Dose	NA	12.0 – NA

Time to First Worsening of Dermatology Quality of Life Index (DLQI) up to Week 48 Secondary · 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.

Worsening of DLQI up to week 48 was defined as a 4-point increase in total score from baseline. Intake of rescue medication, or investigator-prescribed SoC for GPP worsening, was considered as onset of a worsening. The DLQI is a patient-administered, ten-question, quality of life questionnaire that covers six domains including symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Response categories include "not relevant" (score of 0), "not at all" (score of 0), "a little" (score of 1), "a lot" (score of 2) and "very much" (score of 3). Quest

Group	Value	95% CI
Placebo	16.0	4.0 – NA
Spesolimab SC Low Dose	35.8	8.1 – NA
Spesolimab SC Medium Dose	49.3	8.7 – 49.3
Spesolimab SC High Dose	NA	NA – NA

Sustained Remission Secondary · 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.

Proportion of patients with sustained remission at all visits up to Week 48. Proportions were rounded up to three decimal places. Remission was defined as a patient with a GPPGA score of 0 or 1 (clear or almost clear) at all visits up to week 48, without intake of rescue medication, or investigator-prescribed SoC for GPP worsening. GPPGA relied on clinical assessment of the Generalized Pustular Psoriasis (GPP) patient's skin presentation. The GPPGA total score was calculated by taking the mean of the erythema subscore, pustules subscore and scaling/crusting subscore. The severity of each sub

Group	Value	95% CI
Placebo	0.290	0.161 – 0.466
Spesolimab SC Low Dose	0.516	0.348 – 0.680
Spesolimab SC Medium Dose	0.452	0.292 – 0.622
Spesolimab SC High Dose	0.633	0.471 – 0.770

The Occurrence of Treatment Emergent Adverse Events (TEAEs) Secondary · Up to 62 weeks (for detailed timeframe see description).

Percentage of patients with treatment emergent adverse events (TEAEs) is reported. Percentages were rounded up to one decimal places. Time Frame: Placebo, Spesolimab (Speso) SC low, medium, high: From randomized study treatment start until the first use of rescue medication with IV spesolimab or until last dose + 16 weeks, up to 62 weeks. Speso IV SD and Speso IV DD: From first use of rescue medication with IV spesolimab until OL maintenance spesolimab SC or until last dose of spesolimab IV + 16 weeks, up to 17 weeks. Speso OL SC: From the first dose of OL spesolimab SC treatment until last

Group	Value	95% CI
Placebo	86.7
Spesolimab SC Low Dose	90.6
Spesolimab SC Medium Dose	93.5
Spesolimab SC High Dose	86.7
Spesolimab IV SD	68.2
Spesolimab IV DD	60.0
Spesolimab OL SC	75.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Placebo, Spesolimab (Speso) SC low, medium, high: From randomized study treatment start until the first use of rescue medication with IV spesolimab or until last dose + 16 weeks, up to 62 weeks. Speso IV SD and Speso IV DD: From first use of rescue medication with IV spesolimab until OL maintenance spesolimab SC or until last IV dose + 16 weeks, up to 17 weeks. Speso OL SC: From the first dose of OL spesolimab SC treatment until last dose + 16 weeks, up to 62 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/30 (3%)

Deaths: 0/30

Spesolimab SC Low Dose

Serious: 5/32 (16%)

Deaths: 0/32

Spesolimab SC Medium Dose

Serious: 1/31 (3%)

Deaths: 0/31

Spesolimab SC High Dose

Serious: 3/30 (10%)

Deaths: 0/30

Spesolimab IV SD

Serious: 1/22 (5%)

Deaths: 0/22

Spesolimab IV DD

Serious: 4/10 (40%)

Deaths: 0/10

Spesolimab OL SC

Serious: 1/20 (5%)

Deaths: 0/20

Serious adverse events (17 terms)

Reaction	System	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
Palpitations	Cardiac disorders	—	—	—	—	—	—	—
Oedema	General disorders	—	—	—	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—	—	—	—
Cellulitis	Infections and infestations	—	—	—	—	—	—	—
Encephalitis viral	Infections and infestations	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—
Septic shock	Infections and infestations	—	—	—	—	—	—	—
Skin bacterial infection	Infections and infestations	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Cerebral ischaemia	Nervous system disorders	—	—	—	—	—	—	—
Hypertensive encephalopathy	Nervous system disorders	—	—	—	—	—	—	—
Multiple sclerosis	Nervous system disorders	—	—	—	—	—	—	—
Angioedema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Drug eruption	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Pustular psoriasis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—

Other adverse events (36 terms — click to expand)

Reaction	System	Placebo	Spesolimab SC Low Dose	Spesolimab SC Medium Dose	Spesolimab SC High Dose	Spesolimab IV SD	Spesolimab IV DD	Spesolimab OL SC
Pustular psoriasis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Injection site erythema	General disorders	—	—	—	—	—	—	—
Psoriasis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—
Tryptase increased	Investigations	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Injection site induration	General disorders	—	—	—	—	—	—	—
Injection site pain	General disorders	—	—	—	—	—	—	—
Injection site swelling	General disorders	—	—	—	—	—	—	—
Folliculitis	Infections and infestations	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—
Blood trypsin increased	Investigations	—	—	—	—	—	—	—
Protein urine present	Investigations	—	—	—	—	—	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Joint swelling	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—
Dermatitis contact	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Seborrhoeic dermatitis	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Odynophagia	Gastrointestinal disorders	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—
Chest discomfort	General disorders	—	—	—	—	—	—	—
Hyperlipidaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Palpitations, Oedema, Cholelithiasis, Cellulitis, Encephalitis viral, Pneumonia, Septic shock, Skin bacterial infection.

Data from ClinicalTrials.gov NCT04399837 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Antibodies to watch in 2022.
   Kaplon H, Chenoweth A, Crescioli S, Reichert JM. · · 2022 · cited 245× · PMID 35030985 · DOI 10.1080/19420862.2021.2014296
2. Pathophysiology of Generalized Pustular Psoriasis.
   Marrakchi S, Puig L. · · 2022 · cited 79× · PMID 35061228 · DOI 10.1007/s40257-021-00655-y
3. Spesolimab: First Approval.
   Blair HA. · · 2022 · cited 61× · PMID 36418672 · DOI 10.1007/s40265-022-01801-4
4. Study protocol of the global Effisayil 1 Phase II, multicentre, randomised, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis presenting with an acute flare.
   Choon SE, Lebwohl MG, Marrakchi S, Burden AD, et al · · 2021 · cited 53× · PMID 33785490 · DOI 10.1136/bmjopen-2020-043666
5. IL-1 Family Cytokines in Inflammatory Dermatoses: Pathogenetic Role and Potential Therapeutic Implications.
   Iznardo H, Puig L. · · 2022 · cited 44× · PMID 36012744 · DOI 10.3390/ijms23169479
6. Pustular Psoriasis: From Pathophysiology to Treatment.
   Genovese G, Moltrasio C, Cassano N, Maronese CA, et al · · 2021 · cited 40× · PMID 34944562 · DOI 10.3390/biomedicines9121746
7. Therapeutic Development Based on the Immunopathogenic Mechanisms of Psoriasis.
   Tseng JC, Chang YC, Huang CM, Hsu LC, et al · · 2021 · cited 27× · PMID 34371756 · DOI 10.3390/pharmaceutics13071064
8. Design of Effisayil™ 2: A Randomized, Double-Blind, Placebo-Controlled Study of Spesolimab in Preventing Flares in Patients with Generalized Pustular Psoriasis.
   Morita A, Choon SE, Bachelez H, Anadkat MJ, et al · · 2023 · cited 23× · PMID 36333618 · DOI 10.1007/s13555-022-00835-6