Generalized Pustular Psoriasis
Conditions
Brief summary
This Expanded Access Program in China is open to people with a serious skin disease called Generalized Pustular Psoriasis (GPP). This program provides a medicine called spesolimab to people with a GPP flare-up who have no alternative treatment options. This means that no therapy exists and participation in a clinical study is not possible. Participants get a single infusion of spesolimab into a vein. They can get another spesolimab infusion one week after the first infusion if the doctors think it is helpful. Participants are in the program for about 4 months and visit the study site about 5 times. Participants who benefit from the treatment during that time may repeat the treatment in case they experience a new GPP flare-up. The doctors regularly check participants' health and take note of any unwanted effects.
Interventions
DRUGspesolimab
spesolimab
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Generalized Pustular Psoriasis (GPP), consistent with European Rare and Severe Psoriasis Expert Network (ERASPEN) criteria, defined as primary, sterile, macroscopically visible pustules on non-acral skin (excluding cases where pustulation is restricted to psoriatic plaques). GPP can occur with or without systemic inflammation, with or without plaque-type psoriasis, and be either relapsing (\>1 episode) or persistent (\>3 months). * Patient is experiencing a flare, defined as new or worsening of widespread eruption of sterile macroscopically visible pustules, with or without systemic inflammation, as assessed by the treating physician. * Male or female patients, aged 18 to 75 years at time of enrolment. Women of childbearing potential (WOCBP) must be willing and able to use a highly effective method of birth control per International Council for Harmonization (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. * Signed and dated written informed consent in accordance with International Council for Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the program. * No satisfactory authorized alternative therapy exists, as assessed by the treating physician.
Exclusion criteria
* Women who are pregnant, nursing, or who plan to become pregnant while in the program. \-- Women who stop nursing before study drug administration do not need to be excluded from participating; they should refrain from breastfeeding for 16 weeks after the last spesolimab infusion. * Severe, progressive, or uncontrolled hepatic disease, defined as \>3-fold Upper Limit of Normal (ULN) elevation in Aspartate Transaminase (AST) or Alanine Aminotransferase (ALT) or alkaline phosphatase, or \>2-fold ULN elevation in total bilirubin. * Active systemic infections (fungal and bacterial disease) during the last 2 weeks prior to drug administration, as assessed by the treating physician. * Increased risk of infectious complications (e.g. recent pyogenic infection, any congenital or acquired immunodeficiency (e.g. Human Immunodeficiency Virus (HIV)), past organ or stem cell transplantation), as assessed by the treating physician. * Relevant chronic or acute infections, including active tuberculosis (TB), HIV infection or viral hepatitis at the time of drug administration. * Patients should be evaluated for TB infection prior to initiating treatment with spesolimab. * Anti-TB therapy should be considered, in accordance with local guidelines, prior to initiating spesolimab in patients with latent TB or a history of TB. * History of allergy / hypersensitivity to systemically administered spesolimab or its excipients. * 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. * Immediate life-threatening flare of GPP requiring intensive care treatment according to the investigator's judgement. Life-threatening complications include cardiovascular / cytokine driven shock, pulmonary distress syndrome, or renal failure. Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment Emergent Adverse Events (AEs) | From initial drug administration to: end of study treatment + residual effect period or end of study visit. Up to 16 weeks for the single dose group and up to 17 weeks for the double dose group. | This outcome measured the number of patients with any treatment-emergent adverse event (AE). Treatment-emergent AEs are untoward medical events that appear or worsen during treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Treatment Emergent Serious Adverse Events (SAEs) | From initial drug administration to: end of study treatment + residual effect period or end of study visit. Up to 16 weeks for the single dose group and up to 17 weeks for the double dose group. | This outcome measured the number of patients with serious adverse events (SAEs). SAEs are untoward medical occurrences that result in death, are life threatening, require inpatient hospitalisation, require prolongation of existing hospitalisation, result in persistent or significant disability/incapacity, result in a congenital anomaly/birth defect, or are deemed serious for any other medically important reason. |
| Occurrence of Treatment Emergent Adverse Events of Special Interest (AESIs) | From initial drug administration to: end of study treatment + residual effect period or end of study visit. Up to 16 weeks for the single dose group and up to 17 weeks for the double dose group. | This outcome measured the number of patients with any treatment-emergent adverse event of special interest (AESIs). AESIs relates to any specific AE that has been identified at the project level as being of particular concern for prospective safety monitoring and safety assessment within this program. Potential severe DILIs (drug-induced liver injury), systemic hypersensitivity reactions, severe infections, opportunistic and mycobacterium tuberculosis infections, and peripheral neuropathy were considered as AESIs. |
Countries
China
Participant flow
Recruitment details
Open-label, multi-centre, single-arm trial, designed to provide early spesolimab to patients with Generalized Pustular Psoriasis (GPP) presenting with a flare and for whom no satisfactory authorised alternative therapy exists and who are unable to participate in a clinical trial, as assessed by the treating physician.
Pre-assignment details
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the project at any time for any reason given. Close monitoring of all subjects was adhered to throughout the expanded access program (EAP) conduct.
Participants by arm
| Arm | Count |
|---|---|
| Spesolimab Single Dose Treatment Patients with Generalized Pustular Psoriasis (GPP) presenting a flare received a single intravenous dose of 900 milligrams of spesolimab. | 24 |
| Spesolimab Double Dose Treatment Patients with Generalized Pustular Psoriasis (GPP) presenting a flare received a single intravenous dose of 900 milligrams of spesolimab. One week after the initial dose, patients received a second intravenous single dose of 900 mg of spesolimab due to persistence of flare symptoms. | 15 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Spesolimab Single Dose Treatment | Spesolimab Double Dose Treatment | Total |
|---|---|---|---|
| Age, Continuous | 39.9 Years STANDARD_DEVIATION 14.7 | 38.3 Years STANDARD_DEVIATION 15 | 39.3 Years STANDARD_DEVIATION 14.6 |
| Race/Ethnicity, Customized Asian | 24 Participants | 15 Participants | 39 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 24 Participants | 15 Participants | 39 Participants |
| Sex: Female, Male Female | 14 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 10 Participants | 6 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 15 |
| other Total, other adverse events | 15 / 24 | 11 / 15 |
| serious Total, serious adverse events | 1 / 24 | 2 / 15 |
Outcome results
Primary
Occurrence of Treatment Emergent Adverse Events (AEs)
This outcome measured the number of patients with any treatment-emergent adverse event (AE). Treatment-emergent AEs are untoward medical events that appear or worsen during treatment.
Time frame: From initial drug administration to: end of study treatment + residual effect period or end of study visit. Up to 16 weeks for the single dose group and up to 17 weeks for the double dose group.
Population: Treated set: all patients who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimab Single Dose Treatment | Occurrence of Treatment Emergent Adverse Events (AEs) | 18 Participants |
| Spesolimab Double Dose Treatment | Occurrence of Treatment Emergent Adverse Events (AEs) | 12 Participants |
Secondary
Occurrence of Treatment Emergent Adverse Events of Special Interest (AESIs)
This outcome measured the number of patients with any treatment-emergent adverse event of special interest (AESIs). AESIs relates to any specific AE that has been identified at the project level as being of particular concern for prospective safety monitoring and safety assessment within this program. Potential severe DILIs (drug-induced liver injury), systemic hypersensitivity reactions, severe infections, opportunistic and mycobacterium tuberculosis infections, and peripheral neuropathy were considered as AESIs.
Time frame: From initial drug administration to: end of study treatment + residual effect period or end of study visit. Up to 16 weeks for the single dose group and up to 17 weeks for the double dose group.
Population: Treated set: all patients who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimab Single Dose Treatment | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESIs) | 1 Participants |
| Spesolimab Double Dose Treatment | Occurrence of Treatment Emergent Adverse Events of Special Interest (AESIs) | 1 Participants |
Secondary
Occurrence of Treatment Emergent Serious Adverse Events (SAEs)
This outcome measured the number of patients with serious adverse events (SAEs). SAEs are untoward medical occurrences that result in death, are life threatening, require inpatient hospitalisation, require prolongation of existing hospitalisation, result in persistent or significant disability/incapacity, result in a congenital anomaly/birth defect, or are deemed serious for any other medically important reason.
Time frame: From initial drug administration to: end of study treatment + residual effect period or end of study visit. Up to 16 weeks for the single dose group and up to 17 weeks for the double dose group.
Population: Treated set: all patients who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimab Single Dose Treatment | Occurrence of Treatment Emergent Serious Adverse Events (SAEs) | 1 Participants |
| Spesolimab Double Dose Treatment | Occurrence of Treatment Emergent Serious Adverse Events (SAEs) | 2 Participants |