Psoriasis
Conditions
Keywords
psoriasis
Brief summary
The purpose of this study is to determine whether AN2728 topical ointment is a safe and effective treatment for mild-to-moderate plaque-type psoriasis.
Interventions
AN2728 ointment, 2%, applied twice daily for 12 weeks
DRUGOintment Vehicle
Ointment Vehicle, applied twice daily for 12 weeks
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of stable mild-to-moderate plaque-type psoriasis involving 2-35% of total body surface area (BSA) excluding face, scalp, and genitals * Willingness and ability to apply study medication as directed, comply with study instructions, and commit to attending all study visits * Women of childbearing potential must agree to use contraception for the entire study period
Exclusion criteria
* Any dermatological conditions that could interfere with clinical evaluations * Concurrent or recent use of certain topical or systemic medications without a sufficient washout period * Significant confounding conditions as assessed by study doctor * Participated in any other trial of an investigational drug within 30 days or participation in a research study concurrent with this study * Use of lithium- or hydroxychloroquine-containing products (e.g., Plaquenil) * Use of a beta-blocking medication (e.g., propranolol) if the dose has not been stabilized for at least 3 months * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Day 84 | Day 84 | PGA assessed severity of overall disease activity in participants. It was performed using a 6-point scale graded from 0 - 5, in which 0 = clear (no plaque elevation above normal skin level), 1 = almost clear (essentially flat with possible trace elevation), 2 = mild (slight but definite elevation of plaque above normal skin level), 3 = moderate (moderate elevation with rounded or sloped edges to plaque), 4 = severe (marked elevation with hard, sharp edges to plaque), 5 = very severe (very marked elevation with very hard, sharp edges to plaque). The success in PGA of disease severity was defined as a PGA score of '0 = clear' or '1 = almost clear', with at least 2-grade improvement in PGA from Baseline to Day 84. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Percentage of Body Surface Area (%BSA) Involved With Psoriasis at Day 84 | Baseline (Day 1), Day 84 | Percentage of the total body surface area (BSA) involved with psoriasis was measured. Change from Baseline (Day 1) in percentage of BSA at Day 84 was reported. |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline (Day 1) up to Day 84 | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE. |
| Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 14, Day 28, Day 42, Day 56, Day 70 | PGA assessed severity of overall disease activity in participants. It was performed using a 6-point scale graded from 0 - 5, in which 0 = clear (no plaque elevation above normal skin level), 1 = almost clear (essentially flat with possible trace elevation), 2 = mild (slight but definite elevation of plaque above normal skin level), 3 = moderate (moderate elevation with rounded or sloped edges to plaque), 4 = severe (marked elevation with hard, sharp edges to plaque), 5 = very severe (very marked elevation with very hard, sharp edges to plaque). The success in PGA of disease severity was defined as a PGA score of '0 = clear' or '1 = almost clear', with at least 2-grade improvement in PGA from Baseline to Day 14, 28, 42, 56 and 70. |
| Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Baseline (Day 1) up to Day 84 | Local tolerability in participants was evaluated in terms of presence and absence of burning/stinging symptom and its severity in the areas of body where medication was applied. Burning/stinging symptoms were graded on a 4-point scale of 0 - 3 where 0 =none (no stinging/ burning), 1 =mild (slight warm, tingling sensation), 2 = moderate (definite warm; tingling/stinging sensation), 3 = severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores=Severe symptoms. In this outcome measure, number of participants with none, mild, moderate and severe burning/stinging symptoms were reported. |
| Number of Participants With Local Tolerability Symptoms: Pruritus | Baseline (Day 1) up to Day 84 | Local tolerability was evaluated in participants in terms of presence and absence of pruritus symptom and its severity in the areas of body where medication was applied. Pruritus symptoms were graded on a 4-point scale of 0 - 3 where 0 =none (no pruritus), 1 =mild (occasional, slight itching/scratching), 2 = moderate (constant or intermittent itching/scratching which was not disturbing sleep), 3 = severe (bothersome itching/scratching which was disturbing sleep). Higher scores=Severe symptoms. In this outcome measure, number of participants with none, mild, moderate and severe pruritus symptoms were reported. |
| Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Baseline (Day 1) up to Day 84 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were classified according to the severity in 3 categories a) mild =AEs does not interfere with participant's usual function b) moderate =AEs interfered to some extent with participant's usual function c) severe =AEs interfered significantly with participant's usual function and required systemic drug therapy. Treatment-emergent were events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pretreatment state. In this outcome measure, number of mild, moderate and severe TEAEs were reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AN2728 Ointment, 2% AN2728 ointment, 2% was applied topically twice daily to all psoriasis plaques within each participant for 12 weeks (84 days). Plaques were identified at Baseline (Day 1) by the investigator. | 46 |
| AN2728 Ointment, Vehicle AN2728 ointment vehicle was applied topically twice daily to all psoriasis plaques within each participant for 12 weeks (84 days). Plaques were identified at Baseline (Day 1) by the investigator. | 22 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | AN2728 Ointment, 2% | AN2728 Ointment, Vehicle | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 41 Participants | 20 Participants | 61 Participants |
| Sex: Female, Male Female | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 34 Participants | 13 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 23 / 46 | 12 / 22 |
| serious Total, serious adverse events | 0 / 46 | 2 / 22 |
Outcome results
Primary
Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Day 84
PGA assessed severity of overall disease activity in participants. It was performed using a 6-point scale graded from 0 - 5, in which 0 = clear (no plaque elevation above normal skin level), 1 = almost clear (essentially flat with possible trace elevation), 2 = mild (slight but definite elevation of plaque above normal skin level), 3 = moderate (moderate elevation with rounded or sloped edges to plaque), 4 = severe (marked elevation with hard, sharp edges to plaque), 5 = very severe (very marked elevation with very hard, sharp edges to plaque). The success in PGA of disease severity was defined as a PGA score of '0 = clear' or '1 = almost clear', with at least 2-grade improvement in PGA from Baseline to Day 84.
Time frame: Day 84
Population: ITT population included all randomized participants who received the study medication. Missing data was imputed using last observation carried forward (LOCF) method.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AN2728 Ointment, 2% | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Day 84 | 17.4 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Day 84 | 13.6 percentage of participants |
Comparison: Difference in percentage was calculated as values of AN2728 Ointment, 2% group minus values of AN2728 Ointment, Vehicle group.95% CI: [-14.3, 21.8]
Secondary
Change From Baseline in Percentage of Body Surface Area (%BSA) Involved With Psoriasis at Day 84
Percentage of the total body surface area (BSA) involved with psoriasis was measured. Change from Baseline (Day 1) in percentage of BSA at Day 84 was reported.
Time frame: Baseline (Day 1), Day 84
Population: ITT population included all randomized participants who received the study medication. Missing data was imputed using LOCF method.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AN2728 Ointment, 2% | Change From Baseline in Percentage of Body Surface Area (%BSA) Involved With Psoriasis at Day 84 | -2.1 percentage of body surface area | Standard Deviation 3.2 |
| AN2728 Ointment, Vehicle | Change From Baseline in Percentage of Body Surface Area (%BSA) Involved With Psoriasis at Day 84 | -1.4 percentage of body surface area | Standard Deviation 3.22 |
Secondary
Number of Participants With Local Tolerability Symptoms: Burning/Stinging
Local tolerability in participants was evaluated in terms of presence and absence of burning/stinging symptom and its severity in the areas of body where medication was applied. Burning/stinging symptoms were graded on a 4-point scale of 0 - 3 where 0 =none (no stinging/ burning), 1 =mild (slight warm, tingling sensation), 2 = moderate (definite warm; tingling/stinging sensation), 3 = severe (hot, tingling/stinging sensation that caused definite discomfort). Higher scores=Severe symptoms. In this outcome measure, number of participants with none, mild, moderate and severe burning/stinging symptoms were reported.
Time frame: Baseline (Day 1) up to Day 84
Population: Safety population included all randomized participants with confirmed usage of the study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | None | 31 participants |
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Mild | 5 participants |
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Moderate | 4 participants |
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Severe | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Severe | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | None | 18 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Moderate | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Burning/Stinging | Mild | 1 participants |
Secondary
Number of Participants With Local Tolerability Symptoms: Pruritus
Local tolerability was evaluated in participants in terms of presence and absence of pruritus symptom and its severity in the areas of body where medication was applied. Pruritus symptoms were graded on a 4-point scale of 0 - 3 where 0 =none (no pruritus), 1 =mild (occasional, slight itching/scratching), 2 = moderate (constant or intermittent itching/scratching which was not disturbing sleep), 3 = severe (bothersome itching/scratching which was disturbing sleep). Higher scores=Severe symptoms. In this outcome measure, number of participants with none, mild, moderate and severe pruritus symptoms were reported.
Time frame: Baseline (Day 1) up to Day 84
Population: Safety population included all randomized participants with confirmed usage of the study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Pruritus | Moderate | 5 participants |
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Pruritus | Severe | 4 participants |
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Pruritus | None | 23 participants |
| AN2728 Ointment, 2% | Number of Participants With Local Tolerability Symptoms: Pruritus | Mild | 8 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Pruritus | Mild | 6 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Pruritus | Moderate | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Pruritus | None | 13 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Local Tolerability Symptoms: Pruritus | Severe | 0 participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE.
Time frame: Baseline (Day 1) up to Day 84
Population: Safety population included all randomized participants with confirmed usage of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2% | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 23 participants |
| AN2728 Ointment, 2% | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 12 participants |
| AN2728 Ointment, Vehicle | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 participants |
Secondary
Number of Treatment-Emergent Adverse Events (TEAEs) by Severity
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were classified according to the severity in 3 categories a) mild =AEs does not interfere with participant's usual function b) moderate =AEs interfered to some extent with participant's usual function c) severe =AEs interfered significantly with participant's usual function and required systemic drug therapy. Treatment-emergent were events between first dose of study drug and up to Day 84 that were absent before treatment or that worsened relative to pretreatment state. In this outcome measure, number of mild, moderate and severe TEAEs were reported.
Time frame: Baseline (Day 1) up to Day 84
Population: Safety population included all randomized participants with confirmed usage of the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2% | Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild | 14 adverse events |
| AN2728 Ointment, 2% | Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate | 25 adverse events |
| AN2728 Ointment, 2% | Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe | 5 adverse events |
| AN2728 Ointment, Vehicle | Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Severe | 5 adverse events |
| AN2728 Ointment, Vehicle | Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Mild | 11 adverse events |
| AN2728 Ointment, Vehicle | Number of Treatment-Emergent Adverse Events (TEAEs) by Severity | Moderate | 5 adverse events |
Secondary
Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70
PGA assessed severity of overall disease activity in participants. It was performed using a 6-point scale graded from 0 - 5, in which 0 = clear (no plaque elevation above normal skin level), 1 = almost clear (essentially flat with possible trace elevation), 2 = mild (slight but definite elevation of plaque above normal skin level), 3 = moderate (moderate elevation with rounded or sloped edges to plaque), 4 = severe (marked elevation with hard, sharp edges to plaque), 5 = very severe (very marked elevation with very hard, sharp edges to plaque). The success in PGA of disease severity was defined as a PGA score of '0 = clear' or '1 = almost clear', with at least 2-grade improvement in PGA from Baseline to Day 14, 28, 42, 56 and 70.
Time frame: Day 14, Day 28, Day 42, Day 56, Day 70
Population: ITT population included all randomized participants who received the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AN2728 Ointment, 2% | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 28 | 8.7 percentage of participants |
| AN2728 Ointment, 2% | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 56 | 21.7 percentage of participants |
| AN2728 Ointment, 2% | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 42 | 26.1 percentage of participants |
| AN2728 Ointment, 2% | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 70 | 17.4 percentage of participants |
| AN2728 Ointment, 2% | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 14 | 2.2 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 70 | 13.6 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 14 | 0 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 28 | 4.5 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 42 | 18.2 percentage of participants |
| AN2728 Ointment, Vehicle | Percentage of Participants Who Achieved Success in Physician's Global Assessment (PGA) of Disease Severity at Days 14, 28, 42, 56, and 70 | Day 56 | 13.6 percentage of participants |