Palmoplantar Pustulosis
Conditions
Brief summary
This study is open to people with palmoplantar pustulosis who took part in previous clinical studies of a medicine called spesolimab. Participants who benefited from spesolimab treatment in the previous studies can join this study. The purpose of this study is to find out how safe spesolimab is and whether it helps people with palmoplantar pustulosis in the long-term. Participants are in this study for up to 5 years. During this time they visit the study site every month to get spesolimab injections under the skin. At study visits, doctors check the severity of participants' palmoplantar pustulosis and collect information on any health problems of the participants.
Interventions
DRUGSpesolimab
Spesolimab
Sponsors
Boehringer Ingelheim
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed and dated written informed consent for the current trial 1368-0024, in accordance with ICH-GCP and local legislation prior to admission to the current trial * Male or female patients who have completed the treatment period in one of the parent trials without premature discontinuation * Patients who have obtained an individual health benefit, per investigator judgement (e.g. PPP PGA of 0 (clear) or 1 (almost clear) or other clinical improvement), from treatment in the parent trial * 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
Exclusion criteria
* Women who are pregnant, nursing, or who plan to become pregnant while in the trial * Patients who experienced study treatment-limiting adverse events during the parent trial * Severe, progressive, or uncontrolled condition such as renal, hepatic, haematological, endocrine, pulmonary, cardiac, neurologic, cerebral, or psychiatric disease, or signs and symptoms thereof * Patients with congestive heart disease, as assessed by the investigator * Patient with a transplanted organ (with exception of a corneal transplant \> 12 weeks prior to screening in parent trial) 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 (e.g. splenomegaly) * Any documented active or suspected malignancy or history of malignancy at screening, except appropriately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix * Patients who have developed active or severe infective disease and opportunistic infections/infective diseases * Further
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | From first administration of study drug until last administration of study drug + 112 days, up to 869 days. | TEAEs were defined as all adverse events (AEs) occurring between start of treatment in this extension trial and the end of its residual effect period. Adverse events that started before first intake of trial medication in the extension trial and deteriorated under treatment during the extension trial were also considered as 'treatment-emergent'. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) From Baseline in Parent Trial (NCT04015518) at Weeks 48 and 96 | Week 0 (baseline) and Week 48, Week 96 | Percent change in PPP ASI from baseline in parent trial is reported. The adaptation from Psoriasis Area and Severity Index was used in this trial. The index is a linear combination of the percent of surface area of skin affected on the palms and soles of the body and the severity of erythema (E), pustules (P) and scaling / desquamation (D), providing a numeric score for the overall PPP disease state, ranging from 0 (best outcome) to 72 (worst outcome), calculated as: PPP ASI = \[(E+P+D) Area x 0.2 (right palm)\] + \[(E+P+D) Area x 0.2 (left palm)\] + \[(E+P+D) Area x 0.3 (right sole)\] + \[(E+P+D) Area x 0.3 (left sole)\]. The weighted sum of the scores obtained for Erythema (E), Pustules (P), desquamation (D) (scaling) were based on a score range from 0: None to 4: Very severe, and the area affected on a score range from 0 (0%) to 6 (90-100%). Percent change was calculated as: (PPP ASI at Week X - PPP ASI at baseline in parent trial)/PPP ASI at baseline in parent trial \* 100%. |
| Proportion of Patients With PPP ASI50 Compared to Baseline in Parent Trial (NCT04015518) at Weeks 48, 96 | Week 0 (baseline) and Week 48, Week 96 | Proportion of patients achieving a 50% decrease in PPP ASI compared to baseline in the parent trial at Weeks 48 and 96 is reported. The calculated index is a linear combination of the percent of surface area of skin affected on the palms and soles of the body and the severity of erythema, pustules and scaling / desquamation, providing a numeric score for the overall PPP disease state, ranging from 0 (best outcome) to 72 (worst outcome), calculated as: PPP ASI = \[(E+P+D) Area x 0.2 (right palm)\] + \[(E+P+D) Area x 0.2 (left palm)\] + \[(E+P+D) Area x 0.3 (right sole)\] + \[(E+P+D) Area x 0.3 (left sole)\]. The weighted sum of the scores obtained for Erythema (E), Pustules (P), desquamation (D) (scaling) were based on a score range from 0: None to 4: Very severe, and the area affected from 0 (0%) to 6 (90-100%). Proportion was calculated as: Patients with PPP ASI50 at Week X/number of evaluable patients at Week X. Non-response imputation (NRI) was used for missing data imputation. |
| Proportion of Patients With PPP PGA of 0 (Clear) or 1 (Almost Clear) at Week 48, 96 | Week 48 and Week 96 | Proportion of patients with PPP PGA of 0 (clear) or 1 (almost clear) is reported. The Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) was used to assess the patient's skin presentation on the palms and soles. The investigator scored the individual components (erythema, pustules and scaling/crusting) from 0 to 4 as clear, almost clear, mild, moderate or severe. The PPP PGA was analyzed as PPP PGA total score including erythema, pustules and scaling, and as PPP PGA pustules score for pustules only. Number of patients with PPP PGA of 0/1 at Week X/number of evaluable patients at Week X was calculated. NRI approach was used for missing data imputation. The PPP PGA total score was derived as the mean of all individual components: 0 = If mean=0, for all three components: 1. = If 0 \< mean \<1.5 2. = If 1.5 \<= mean \<2.5 3. = If 2.5 \<= mean \<3.5 4. = If mean \>=3.5 |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Japan, Poland, Russia, South Korea, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This study was a phase II, open-label, single arm, to test the safety and efficacy of long-term treatment with Spesolimab in patients with Palmoplantar Pustulosis (PPP) who took part in previous studies with Spesolimab
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Spesolimab (BI 655130) The patients were administered 600 milligram (mg) Spesolimab (BI 655130) prefilled syringes subcutaneously in thighs or abdomen every 4 weeks for up to 5 years (260 weeks). Patients were to continue the treatment until no longer benefited under the patient opinion or investigator assessment, or withdrawal of consent, whichever occurred first. | 108 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 5 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Termination of the trial by the sponsor | 89 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Spesolimab (BI 655130) |
|---|---|
| Age, Continuous | 55.2 Years STANDARD_DEVIATION 10.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Palmoplantar Pustulosis Area and Severity Index (PPP ASI) | 24.97 Score in a scale STANDARD_DEVIATION 10.93 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 39 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 69 Participants |
| Sex: Female, Male Female | 75 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 108 |
| other Total, other adverse events | 77 / 108 |
| serious Total, serious adverse events | 19 / 108 |
Outcome results
Primary
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
TEAEs were defined as all adverse events (AEs) occurring between start of treatment in this extension trial and the end of its residual effect period. Adverse events that started before first intake of trial medication in the extension trial and deteriorated under treatment during the extension trial were also considered as 'treatment-emergent'.
Time frame: From first administration of study drug until last administration of study drug + 112 days, up to 869 days.
Population: Treated Set for Maintenance Treatment (TS-MT):~This patient set included all patients who received at least one dose of the maintenance treatment 600 mg s.c. every 4 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Spesolimab (BI 655130) | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | 96 Participants |
Secondary
Percent Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) From Baseline in Parent Trial (NCT04015518) at Weeks 48 and 96
Percent change in PPP ASI from baseline in parent trial is reported. The adaptation from Psoriasis Area and Severity Index was used in this trial. The index is a linear combination of the percent of surface area of skin affected on the palms and soles of the body and the severity of erythema (E), pustules (P) and scaling / desquamation (D), providing a numeric score for the overall PPP disease state, ranging from 0 (best outcome) to 72 (worst outcome), calculated as: PPP ASI = \[(E+P+D) Area x 0.2 (right palm)\] + \[(E+P+D) Area x 0.2 (left palm)\] + \[(E+P+D) Area x 0.3 (right sole)\] + \[(E+P+D) Area x 0.3 (left sole)\]. The weighted sum of the scores obtained for Erythema (E), Pustules (P), desquamation (D) (scaling) were based on a score range from 0: None to 4: Very severe, and the area affected on a score range from 0 (0%) to 6 (90-100%). Percent change was calculated as: (PPP ASI at Week X - PPP ASI at baseline in parent trial)/PPP ASI at baseline in parent trial \* 100%.
Time frame: Week 0 (baseline) and Week 48, Week 96
Population: Safety analysis set for maintenance treatment (SAF-MT) This patient set included all patients who received at least one dose of the maintenance treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Spesolimab (BI 655130) | Percent Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) From Baseline in Parent Trial (NCT04015518) at Weeks 48 and 96 | Week 48 | -76.85 Percent change | Standard Deviation 22.63 |
| Spesolimab (BI 655130) | Percent Change in Palmoplantar Pustulosis Area and Severity Index (PPP ASI) From Baseline in Parent Trial (NCT04015518) at Weeks 48 and 96 | Week 96 | -77.58 Percent change | Standard Deviation 18.59 |
Secondary
Proportion of Patients With PPP ASI50 Compared to Baseline in Parent Trial (NCT04015518) at Weeks 48, 96
Proportion of patients achieving a 50% decrease in PPP ASI compared to baseline in the parent trial at Weeks 48 and 96 is reported. The calculated index is a linear combination of the percent of surface area of skin affected on the palms and soles of the body and the severity of erythema, pustules and scaling / desquamation, providing a numeric score for the overall PPP disease state, ranging from 0 (best outcome) to 72 (worst outcome), calculated as: PPP ASI = \[(E+P+D) Area x 0.2 (right palm)\] + \[(E+P+D) Area x 0.2 (left palm)\] + \[(E+P+D) Area x 0.3 (right sole)\] + \[(E+P+D) Area x 0.3 (left sole)\]. The weighted sum of the scores obtained for Erythema (E), Pustules (P), desquamation (D) (scaling) were based on a score range from 0: None to 4: Very severe, and the area affected from 0 (0%) to 6 (90-100%). Proportion was calculated as: Patients with PPP ASI50 at Week X/number of evaluable patients at Week X. Non-response imputation (NRI) was used for missing data imputation.
Time frame: Week 0 (baseline) and Week 48, Week 96
Population: Safety analysis set for maintenance treatment (SAF-MT) This patient set included all patients who received at least one dose of the maintenance treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Spesolimab (BI 655130) | Proportion of Patients With PPP ASI50 Compared to Baseline in Parent Trial (NCT04015518) at Weeks 48, 96 | Week 48 | 0.770 Proportion of participants |
| Spesolimab (BI 655130) | Proportion of Patients With PPP ASI50 Compared to Baseline in Parent Trial (NCT04015518) at Weeks 48, 96 | Week 96 | 0.683 Proportion of participants |
Secondary
Proportion of Patients With PPP PGA of 0 (Clear) or 1 (Almost Clear) at Week 48, 96
Proportion of patients with PPP PGA of 0 (clear) or 1 (almost clear) is reported. The Palmoplantar Pustulosis Physician Global Assessment (PPP PGA) was used to assess the patient's skin presentation on the palms and soles. The investigator scored the individual components (erythema, pustules and scaling/crusting) from 0 to 4 as clear, almost clear, mild, moderate or severe. The PPP PGA was analyzed as PPP PGA total score including erythema, pustules and scaling, and as PPP PGA pustules score for pustules only. Number of patients with PPP PGA of 0/1 at Week X/number of evaluable patients at Week X was calculated. NRI approach was used for missing data imputation. The PPP PGA total score was derived as the mean of all individual components: 0 = If mean=0, for all three components: 1. = If 0 \< mean \<1.5 2. = If 1.5 \<= mean \<2.5 3. = If 2.5 \<= mean \<3.5 4. = If mean \>=3.5
Time frame: Week 48 and Week 96
Population: Safety analysis set for maintenance treatment (SAF-MT) This patient set included all patients who received at least one dose of the maintenance treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Spesolimab (BI 655130) | Proportion of Patients With PPP PGA of 0 (Clear) or 1 (Almost Clear) at Week 48, 96 | Week 48 | 0.720 Proportion of participants |
| Spesolimab (BI 655130) | Proportion of Patients With PPP PGA of 0 (Clear) or 1 (Almost Clear) at Week 48, 96 | Week 96 | 0.707 Proportion of participants |