Palmoplantar Pustulosis
Conditions
Keywords
PPP
Brief summary
A study to evaluate the efficacy and safety, and pharmacokinetic (PK) profile of multiple doses of imsidolimab (ANB019) in adults with palmoplantar pustulosis (PPP)
Interventions
BIOLOGICALImsidolimab
Administered by subcutaneous injection once a month
DRUGPlacebo
Administered by subcutaneous injection once a month
Sponsors
Vanda Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Clinically confirmed diagnosis of PPP * Disease duration of at least 6 months prior to screening * Present with active pustules on palms or/and soles at screening
Exclusion criteria
* Any other ongoing inflammatory disease that interfere with the investigator's ability to evaluate the subject's response to therapy * History of recurrent or active/serious infection * Ongoing use of psoriasis prohibited medication Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI) | Baseline to Week 16 | The Palmoplantar Pustulosis Area and Severity Index (PPPASI) is used to assess the severity of palmoplantar pustulosis lesions and their response to therapy. The glabrous skin of both palms and both soles are assessed for erythema, pustules, and desquamation (scaling), each on a scale from 0 (none) to 4 (very severe). The area affected of each palm and sole is scored from 0 (0%) to 6 (90-100%). Scores for the 3 characteristics of PPP are summed and adjusted for the area affected, and the scores for each palm and sole are added to calculate the total score. The PPPASI total score ranges from 0 to 72. A higher score indicates more severe disease, and a negative change from Baseline indicates improvement. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | From first dose of any study drug to Week 24 | Clinical safety was evaluated by reporting incidence of adverse events up to week 24. TEAEs are defined as new events that occured during or after first dose of study drug or any event that worsens after first dose of study drug. A serious AE (SAE) is defined as any untoward medical occurrence that resulted in death, was life-threatening, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or an important medical event that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Severity was assessed by the Investigator as mild (easily tolerated, causing minimal discomfort and not interfering with everyday activities), moderate (causes sufficient discomfort and interferes with normal everyday activities) or severe (prevents normal everyday activities). The Investigator assessed the relationship between study treatment and each AE based on clinical judgement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved 50% Reduction (Improvement) From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index Score (PPPASI 50) | Baseline to Week 16 | The Palmoplantar Pustulosis Area and Severity Index (PPPASI) is used to assess the severity of palmoplantar pustulosis lesions and their response to therapy. The glabrous skin of both palms and both soles are assessed for erythema, pustules, and desquamation (scaling), each on a scale from 0 (none) to 4 (very severe). The area affected of each palm and sole is scored from 0 (0%) to 6 (90-100%). Scores for the 3 characteristics of PPP are summed and adjusted for the area affected, and the scores for each palm and sole are added to calculate the total score. The PPPASI total score ranges from 0 to 72. A higher score indicates more severe disease. |
| Percentage of Participants Who Achieved a Clear or Almost Clear Palmoplantar Pustulosis Investigator's Global Assessment (PPPIGA) Score at Week 16 | Week 16 | The Investigator rated the severity of participants' disease on the following 5-point scale: * 0: Clear - No signs of palmoplantar pustulosis; no scaling or crusts or pustules remain; * 1: Almost clear - Slight scaling and/or erythema and/or slight crusts; very few (yellow) and/or old (brown) pustules; * 2: Mild - Scaling and/or erythema and/or crusts; visible new (yellow) and/or old (brown) pustules of limited number and extent; * 3: Moderate - Prominent scaling and/or erythema and/or crusting; prominent new (yellow) and/or old (brown) pustules covering most of the area involved; * 4: Severe - Severe scaling and/or erythema and/or crusting; numerous new (yellow) and/or old (brown) pustules with / without major confluence, covering the entire area of at least 2 palmoplantar sites. |
Countries
Canada, Germany, Poland, United States
Participant flow
Recruitment details
Participants were enrolled in this trial at 36 sites located within North America and Europe.
Pre-assignment details
Participants were randomized equally to one of two treatment groups. Randomization was stratified based on the participant's history of plaque psoriasis, to ensure that the number of participants enrolled with plaque psoriasis did not exceed 50%.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered by subcutaneous injection on Day 1 followed by monthly doses on Days 29, 57, and 85. | 29 |
| Imsidolimab Participants received 200 mg imsidolimab by subcutaneous injection on Day 1 followed by monthly doses of 100 mg imsidolimab by subcutaneous injection on Days 29, 57, and 85. | 30 |
| Total | 59 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Coronavirus Disease 2019 (COVID-19) Restrictions | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo | Imsidolimab | Total |
|---|---|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 10.59 | 52.3 years STANDARD_DEVIATION 12.1 | 50.1 years STANDARD_DEVIATION 11.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 30 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| History of Plaque Psoriasis No | 22 Participants | 23 Participants | 45 Participants |
| History of Plaque Psoriasis Yes | 7 Participants | 7 Participants | 14 Participants |
| Palmoplantar Pustulosis Psoriasis Area Severity Index Score | 19.47 score on a scale STANDARD_DEVIATION 11.633 | 16.18 score on a scale STANDARD_DEVIATION 8.045 | 17.80 score on a scale STANDARD_DEVIATION 10.022 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 28 Participants | 53 Participants |
| Sex: Female, Male Female | 24 Participants | 22 Participants | 46 Participants |
| Sex: Female, Male Male | 5 Participants | 8 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 20 / 29 | 21 / 30 |
| serious Total, serious adverse events | 1 / 29 | 0 / 30 |
Outcome results
Primary
Change From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI)
The Palmoplantar Pustulosis Area and Severity Index (PPPASI) is used to assess the severity of palmoplantar pustulosis lesions and their response to therapy. The glabrous skin of both palms and both soles are assessed for erythema, pustules, and desquamation (scaling), each on a scale from 0 (none) to 4 (very severe). The area affected of each palm and sole is scored from 0 (0%) to 6 (90-100%). Scores for the 3 characteristics of PPP are summed and adjusted for the area affected, and the scores for each palm and sole are added to calculate the total score. The PPPASI total score ranges from 0 to 72. A higher score indicates more severe disease, and a negative change from Baseline indicates improvement.
Time frame: Baseline to Week 16
Population: Intent-to-treat analysis set with available data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI) | -6.0 score on a scale | Standard Error 1.48 |
| Imsidolimab | Change From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI) | -6.1 score on a scale | Standard Error 1.46 |
Comparison: The change from Baseline in PPPASI at Week 16 was analyzed using a a general linear mixed model for repeated measures (MMRM). The model included fixed effects for treatment, history of plaque psoriasis (Yes/No), visit, treatment by visit interaction, and Baseline PPPASI score as covariate.p-value: 0.94495% CI: [-4.05, 3.77]Mixed-model Repeated Measures (MMRM)
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Clinical safety was evaluated by reporting incidence of adverse events up to week 24. TEAEs are defined as new events that occured during or after first dose of study drug or any event that worsens after first dose of study drug. A serious AE (SAE) is defined as any untoward medical occurrence that resulted in death, was life-threatening, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or an important medical event that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed above. Severity was assessed by the Investigator as mild (easily tolerated, causing minimal discomfort and not interfering with everyday activities), moderate (causes sufficient discomfort and interferes with normal everyday activities) or severe (prevents normal everyday activities). The Investigator assessed the relationship between study treatment and each AE based on clinical judgement.
Time frame: From first dose of any study drug to Week 24
Population: Safety Analysis Set (all randomized participants who received at least 1 dose of imsidolimab or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 20 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE related to study drug | 3 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Severe TEAE | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE of special interest | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study treatment | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to study discontinuation | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE related to injection site reaction | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Disease related TEAE | 6 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to death | 0 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Any treatment-emergent adverse event (TEAE) | 21 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of study treatment | 1 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE related to study drug | 6 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Disease related TEAE | 2 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Severe TEAE | 0 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE leading to study discontinuation | 1 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Serious TEAE | 0 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE related to injection site reaction | 0 Participants |
| Imsidolimab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | TEAE of special interest | 0 Participants |
Secondary
Percentage of Participants Who Achieved 50% Reduction (Improvement) From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index Score (PPPASI 50)
The Palmoplantar Pustulosis Area and Severity Index (PPPASI) is used to assess the severity of palmoplantar pustulosis lesions and their response to therapy. The glabrous skin of both palms and both soles are assessed for erythema, pustules, and desquamation (scaling), each on a scale from 0 (none) to 4 (very severe). The area affected of each palm and sole is scored from 0 (0%) to 6 (90-100%). Scores for the 3 characteristics of PPP are summed and adjusted for the area affected, and the scores for each palm and sole are added to calculate the total score. The PPPASI total score ranges from 0 to 72. A higher score indicates more severe disease.
Time frame: Baseline to Week 16
Population: Intent-to-treat analysis set with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved 50% Reduction (Improvement) From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index Score (PPPASI 50) | 50.0 percentage of participants |
| Imsidolimab | Percentage of Participants Who Achieved 50% Reduction (Improvement) From Baseline in Palmoplantar Pustulosis Psoriasis Area Severity Index Score (PPPASI 50) | 45.8 percentage of participants |
95% CI: [0.288, 2.686]
Secondary
Percentage of Participants Who Achieved a Clear or Almost Clear Palmoplantar Pustulosis Investigator's Global Assessment (PPPIGA) Score at Week 16
The Investigator rated the severity of participants' disease on the following 5-point scale: * 0: Clear - No signs of palmoplantar pustulosis; no scaling or crusts or pustules remain; * 1: Almost clear - Slight scaling and/or erythema and/or slight crusts; very few (yellow) and/or old (brown) pustules; * 2: Mild - Scaling and/or erythema and/or crusts; visible new (yellow) and/or old (brown) pustules of limited number and extent; * 3: Moderate - Prominent scaling and/or erythema and/or crusting; prominent new (yellow) and/or old (brown) pustules covering most of the area involved; * 4: Severe - Severe scaling and/or erythema and/or crusting; numerous new (yellow) and/or old (brown) pustules with / without major confluence, covering the entire area of at least 2 palmoplantar sites.
Time frame: Week 16
Population: Intent-to-treat analysis set with available data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Achieved a Clear or Almost Clear Palmoplantar Pustulosis Investigator's Global Assessment (PPPIGA) Score at Week 16 | 12.5 percentage of participants |
| Imsidolimab | Percentage of Participants Who Achieved a Clear or Almost Clear Palmoplantar Pustulosis Investigator's Global Assessment (PPPIGA) Score at Week 16 | 20.8 percentage of participants |
95% CI: [0.5, 13.9]