Generalized Pustular Psoriasis
Conditions
Keywords
GPP
Brief summary
The main objectives of this study are to evaluate the efficacy, safety and tolerability of imsidolimab in adults with active GPP.
Detailed description
Single arm, multiple-dose study evaluating the use of imsidolimab for the treatment of GPP.
Interventions
Humanized monoclonal antibody
Sponsors
Study design
Eligibility
Inclusion criteria
* Diagnosis of active GPP * Japanese Dermatology Association (JDA) severity index total score of at least 6 and erythema with pustules accounting for at least 10% of body surface area or a moderate severity score on Generalized Pustular Psoriasis Physician's Global Assessment (GPPPGA) * Must be candidates for systemic therapy or phototherapy
Exclusion criteria
* Erythrodermic, guttate psoriasis, drug induced GPP * Any other ongoing inflammatory disease that interfere with the Investigator's ability to evaluate the subject's response to therapy * History of recurrent or chronic infection * ongoing use of psoriasis prohibited medication Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Response on the Clinical Global Impression (CGI) Scale | Week 4 and Week 16 | Clinical response was defined as Very much improved, Much Improved, or Minimally Improved on the CGI scale according to the Modified Japanese Dermatological Association Severity Index (JDA-SI) total score. The JDA-SI includes assessment of skin lesions (area of erythema with pustules, area of erythema total, and area of edema) and fever, white blood cell count, C-reactive protein and serum albumin levels. The total score ranges from 0 to 17 (severe). CGI was assessed based on the JDA-SI according to the following: * Very Much Improved: Reduction in JDA-SI total score by 3 or \> points; * Much improved: Reduction in JDA-SI total score by 1 or 2 points; * Minimally improved: No change in JDA-SI total score and area of erythema with pustules reduced by \<20% or clinically meaningful improvement in at least 1 other component of the modified JDA-SI. |
| Percent Change From Baseline in Body Surface Area of Erythema With Pustules at Week 1, Week 4, and Week 16 | Baseline, Week 1, Week 4, and Week 16 | Excluding palms and soles from 0% to 100%. The palmar surface of one hand (using the subject's hand and including the fingers) represents 1% of his or her total BSA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Modified Japanese Dermatological Association - Severity Index (mJDA-SI) Total Skin Lesions Score at Week 1, Week 4, and Week 16 | Baseline, Week 1, Week 4, and Week 16 | The area of erythema with pustules, area of total erythema and area of edema were assessed by the Investigator and scored from 0 to 3 on the following scale: * 0: 0% body surface area (BSA) affected; * 1: \> 0%, \< 10% BSA affected; * 2: ≥ 10%, \< 50% BSA affected; * 3: ≥ 50% BSA affected. The JDA-SI Total Skin Lesions Score is the sum of the area of erythema with pustules score, area of total erythema score and area of edema score and ranges between 0 and 9 (worst). A negative change from Baseline indicates improvement. |
| Percentage of Participants Achieving a Generalized Pustular Psoriasis Physician's Global Assessment (GPPPGA) Score of 0 or 1 at Week 1, Week 4, and Week 16 | Week 1, Week 4, and Week 16 | The GPPPGA scale was used to assess the impact and severity of GPP on the following scale: * 0: Clear (normal skin or post-inflammatory hyperpigmentation, no visible pustules, no scaling or crusting). * 1: Almost clear (faint, diffuse pink or slight red erythema, low density occasional small discrete pustules (noncoalescent), superficial focal scaling or crusting restricted to periphery of lesions). * 2: Mild (light red erythema, moderate density grouped discrete small pustules (noncoalescent), predominantly fine scaling or crusting). * 3: Moderate (bright red erythema, high density pustules with some coalescence, moderate scaling or crusting covering most or all lesions). * 4: Severe (deep fiery red erythema, very high density pustules with pustular lakes, severe scaling or crusting covering most or all lesions). |
| Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 1, Week 4, and Week 16 | Baseline and Week 1, Week 4, and Week 16 | The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that their skin problem has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A negative change from Baseline indicates improvement. |
Countries
Poland, South Korea, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 5 centers that enrolled subjects in the United Kingdom and Poland.
Pre-assignment details
The study included a screening period of up to 42 days, a 12-week treatment period, and a 12-week safety follow-up period. A total of 12 subjects were screened, with 8 subjects being enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Imsidolimab Participants received imsidolimab 750 mg intravenously on Day 1 followed by administration of 3 doses of subcutaneous imsidolimab 100 mg on Days 29, 57, and 85. | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Termination of Study by Investigator | 1 |
| Overall Study | Use of Excluded/Prohibited Medication | 1 |
Baseline characteristics
| Characteristic | Imsidolimab |
|---|---|
| Age, Continuous | 51.3 years STANDARD_DEVIATION 14.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Modified Japanese Dermatological Association Severity Index (JDA-SI) Total Score | 9.1 score on a scale STANDARD_DEVIATION 2.75 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized White | 7 Participants |
| Region of Enrollment Poland | 5 participants |
| Region of Enrollment United Kingdom | 3 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 6 / 8 |
| serious Total, serious adverse events | 2 / 8 |
Outcome results
Percentage of Participants Achieving Clinical Response on the Clinical Global Impression (CGI) Scale
Clinical response was defined as Very much improved, Much Improved, or Minimally Improved on the CGI scale according to the Modified Japanese Dermatological Association Severity Index (JDA-SI) total score. The JDA-SI includes assessment of skin lesions (area of erythema with pustules, area of erythema total, and area of edema) and fever, white blood cell count, C-reactive protein and serum albumin levels. The total score ranges from 0 to 17 (severe). CGI was assessed based on the JDA-SI according to the following: * Very Much Improved: Reduction in JDA-SI total score by 3 or \> points; * Much improved: Reduction in JDA-SI total score by 1 or 2 points; * Minimally improved: No change in JDA-SI total score and area of erythema with pustules reduced by \<20% or clinically meaningful improvement in at least 1 other component of the modified JDA-SI.
Time frame: Week 4 and Week 16
Population: The full analysis set (FAS) included all enrolled participants. Participants with missing data were categorized as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imsidolimab | Percentage of Participants Achieving Clinical Response on the Clinical Global Impression (CGI) Scale | Week 4 | 75.0 percentage of participants |
| Imsidolimab | Percentage of Participants Achieving Clinical Response on the Clinical Global Impression (CGI) Scale | Week 16 | 75.0 percentage of participants |
Percent Change From Baseline in Body Surface Area of Erythema With Pustules at Week 1, Week 4, and Week 16
Excluding palms and soles from 0% to 100%. The palmar surface of one hand (using the subject's hand and including the fingers) represents 1% of his or her total BSA.
Time frame: Baseline, Week 1, Week 4, and Week 16
Population: Full analysis set participants with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imsidolimab | Percent Change From Baseline in Body Surface Area of Erythema With Pustules at Week 1, Week 4, and Week 16 | Week 1 | -59.63 percent change | Standard Deviation 39.895 |
| Imsidolimab | Percent Change From Baseline in Body Surface Area of Erythema With Pustules at Week 1, Week 4, and Week 16 | Week 4 | -94.17 percent change | Standard Deviation 10.737 |
| Imsidolimab | Percent Change From Baseline in Body Surface Area of Erythema With Pustules at Week 1, Week 4, and Week 16 | Week 16 | -97.78 percent change | Standard Deviation 5.443 |
Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 1, Week 4, and Week 16
The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that their skin problem has affected their quality of life in the last week in the following 6 aspects: symptoms and feelings, daily activities, leisure, work or school activities, personal relationships and treatment related feelings. Participants answer the 10 questions on a scale from 0 (not at all) to 3 (very much). The DLQI is calculated by summing the scores of the 10 questions, resulting in a maximum of 30 and a minimum of 0 with higher scores indicating more impaired quality of life. A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 1, Week 4, and Week 16
Population: Full analysis set participants with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imsidolimab | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 1, Week 4, and Week 16 | Week 1 | -0.9 score on a scale | Standard Deviation 0.356 |
| Imsidolimab | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 1, Week 4, and Week 16 | Week 4 | -6.0 score on a scale | Standard Deviation 9.08 |
| Imsidolimab | Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score at Week 1, Week 4, and Week 16 | Week 16 | -10.7 score on a scale | Standard Deviation 9.16 |
Percentage of Participants Achieving a Generalized Pustular Psoriasis Physician's Global Assessment (GPPPGA) Score of 0 or 1 at Week 1, Week 4, and Week 16
The GPPPGA scale was used to assess the impact and severity of GPP on the following scale: * 0: Clear (normal skin or post-inflammatory hyperpigmentation, no visible pustules, no scaling or crusting). * 1: Almost clear (faint, diffuse pink or slight red erythema, low density occasional small discrete pustules (noncoalescent), superficial focal scaling or crusting restricted to periphery of lesions). * 2: Mild (light red erythema, moderate density grouped discrete small pustules (noncoalescent), predominantly fine scaling or crusting). * 3: Moderate (bright red erythema, high density pustules with some coalescence, moderate scaling or crusting covering most or all lesions). * 4: Severe (deep fiery red erythema, very high density pustules with pustular lakes, severe scaling or crusting covering most or all lesions).
Time frame: Week 1, Week 4, and Week 16
Population: Full Analysis Set participants with GPPPGA at Baseline and at each time point
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imsidolimab | Percentage of Participants Achieving a Generalized Pustular Psoriasis Physician's Global Assessment (GPPPGA) Score of 0 or 1 at Week 1, Week 4, and Week 16 | Week 4 | 50.0 percentage of participants |
| Imsidolimab | Percentage of Participants Achieving a Generalized Pustular Psoriasis Physician's Global Assessment (GPPPGA) Score of 0 or 1 at Week 1, Week 4, and Week 16 | Week 1 | 0.0 percentage of participants |
| Imsidolimab | Percentage of Participants Achieving a Generalized Pustular Psoriasis Physician's Global Assessment (GPPPGA) Score of 0 or 1 at Week 1, Week 4, and Week 16 | Week 16 | 75.0 percentage of participants |
Percent Change From Baseline in Modified Japanese Dermatological Association - Severity Index (mJDA-SI) Total Skin Lesions Score at Week 1, Week 4, and Week 16
The area of erythema with pustules, area of total erythema and area of edema were assessed by the Investigator and scored from 0 to 3 on the following scale: * 0: 0% body surface area (BSA) affected; * 1: \> 0%, \< 10% BSA affected; * 2: ≥ 10%, \< 50% BSA affected; * 3: ≥ 50% BSA affected. The JDA-SI Total Skin Lesions Score is the sum of the area of erythema with pustules score, area of total erythema score and area of edema score and ranges between 0 and 9 (worst). A negative change from Baseline indicates improvement.
Time frame: Baseline, Week 1, Week 4, and Week 16
Population: Full analysis set participants with available data at each time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Imsidolimab | Percent Change From Baseline in Modified Japanese Dermatological Association - Severity Index (mJDA-SI) Total Skin Lesions Score at Week 1, Week 4, and Week 16 | Week 1 | -25.74 percent change | Standard Deviation 26.369 |
| Imsidolimab | Percent Change From Baseline in Modified Japanese Dermatological Association - Severity Index (mJDA-SI) Total Skin Lesions Score at Week 1, Week 4, and Week 16 | Week 4 | -55.65 percent change | Standard Deviation 27.157 |
| Imsidolimab | Percent Change From Baseline in Modified Japanese Dermatological Association - Severity Index (mJDA-SI) Total Skin Lesions Score at Week 1, Week 4, and Week 16 | Week 16 | -62.20 percent change | Standard Deviation 29.757 |