Palmoplantar Pustulosis
Conditions
Keywords
PPP, Palmoplantar Pustulosis, Apremilast, Otezla
Brief summary
Multicenter, open-label, single-arm, phase II, pilot study. The screening period was up to 4 weeks and treatment took place over 20 weeks per patient. Five visits per patient were performed including: Visit 1 at week -4 to -1 (screening), Visit 2 at week 0 (baseline), Visit 3 at week 4, Visit 4 at week 12, and Visit 5 at week 20 (end of study). There was no follow-up period.
Detailed description
This was a multicenter, open-label, single-arm, phase II, pilot study to evaluate the efficacy and safety of apremilast involving 21 patients with PPP. The screening period was up to 4 weeks and treatment took place over 20 weeks per patient. No follow up period took place. No extension was done. Recruitment period was 4 months; hence study duration from first patient in to last patient out was approximately 9 months. About 4-6 patients per center were recruited, assuming enrolment of both genders with distribution according to prevalence of condition. Patient recruitment took place at 5 centers in Germany. The investigators had relevant expertise in diagnosing and treating PPP or were specialized in dermatology. Patients were enrolled until approximately 20 patients were included into the study. One drop-out was replaced during the recruitment phase. Five visits per patient were performed including: * Visit 1 at week -4 to -1 (screening) * Visit 2 at week 0 (baseline) * Visit 3 at week 4 * Visit 4 at week 12 * Visit 5 at week 20 (end of study) After the end of study participation the investigator ensured that the patient received a suitable therapy appropriate to patient's condition.
Interventions
DRUGApremilast
Apremilast was taken orally twice daily (except Day 1). Patients received tablets in blister/bottles sufficient for one month. To mitigate potential gastrointestinal side effects (primarily mild-to-moderate nausea and diarrhoea), dose titration was implemented in this study in accordance with the Summary of Product Characteristics (SmPC). A titration pack included tablets of 10, 20 and 30 mg for a period of one month. During the first 5 days, the dosage was up-titrated. The initial dose on day 1 was 10 mg in the morning; this was increased to 10 mg in the morning and evening on day 2. The evening dose was further increased by 10 mg (to 20 mg) on day 3. On day 4, the morning dose was increased to 20 mg, so that 20 mg was taken twice daily, and on day 5 the evening dose was increased to 30 mg. From Day 6 onwards, patients received the 30 mg dose twice a day. Subsequent packs included only tablets of 30 mg strength.
Sponsors
Kristian Reich
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This was an open-label, single-arm, pilot study to evaluate the efficacy and safety of apremilast.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients aged 18 years or more at screening visit. * Patients with chronic PPP (disease history of at least 6 months of diagnosis), who were eligible for treatment with systemic therapy defined as having PPP inadequately controlled by topical treatment and/or phototherapy and/or previous systemic therapy * Patients with chronic moderate to severe PPP defined as patients with a PPPASI ≥12 with or without concomitant plaque-type psoriasis * Negative result of a urine pregnancy test taken at screening and at baseline for all women, except those who were surgically sterile or at least 1 year postmenopausal (i.e. at least 12 consecutive months with amenorrhea without other known or suspected medical cause) * Willingness and capability of using a highly effective contraceptive measures from Screening visit until the end of at least one menstrual cycle (but not less than 28 days) following discontinuation of apremilast as defined below: * Female patient of childbearing potential (fertile, following menarche and until becoming post- menopausal unless permanently sterile) using a highly effective method of contraception OR female patients of non-childbearing potential (surgically sterilized \[e.g. hysterectomy, bilateral salpingectomy and bilateral oophorectomy\] or postmenopausal) * Male patient, and their female partner of childbearing potential, using a highly effective method of contraception * Adequate contraceptive method defined as: * A method with less than 1% failure rate (e.g. permanent sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner) OR * The use of two methods of contraception (e.g. one barrier method \[condom, diaphragm or cervical/vault caps\] with spermicide and one hormonal contraceptive \[e.g. combined oral contraceptives, patch, vaginal ring, injectables and implants\]) * Patient was capable of understanding and giving written, voluntary informed consent before study screening. * Willingness and capability of complying with all study procedure requirements, as per the Investigator's judgment (e.g. patient able to swallow the apremilast tablets, blood sampling).
Exclusion criteria
* General: * Pregnant or breast-feeding women * Current or history of psychiatric disease that would interfere with the ability to comply with the study protocol or give informed consent * Patients known to have had a substance abuse (drug or alcohol) problem within the previous 12 month * Individuals who were involved in the organization of the study * Patients who were in any way dependent on the investigator * Patients who were participating in a clinical study * Relatives, partner or staff of any clinical site personnel * Disease-related: * Evidence of skin conditions (e.g. eczema) other than PPP/psoriasis that would interfere with evaluations of the effect of study medication on PPP or psoriasis. * Laboratory values from routine blood test taken within the 8 weeks prior to screening with any of the following: * Serum creatinine \>1.4 x upper limit of normal (ULN) for age and gender * Estimated Glomerular Filtration Rate (eGFR) \<30 mL/min/1.73m2 according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation * Pustular psoriasis lesions on the part of body other than hands or feet * Significant concurrent medical conditions at the time of screening, including: * Risk factors for renal toxicity (renal inflammation) * Severe hepatic dysfunction * Unstable angina pectoris * Uncompensated congestive heart failure * Severe pulmonary disease requiring hospitalization or supplemental oxygen therapy * Immunodeficiency disorders: primary or secondary * Known positive human immunodeficiency virus (HIV) test result, hepatitis B surface (HBS) antigen or hepatitis C virus (HCV) test result * Uncontrolled insulin-dependent diabetes mellitus * Cancer or history of cancer (except for resected cutaneous basal cell or squamous cell carcinoma) in the last 5 years * Open cutaneous ulcers * Any condition that, in the judgment of the investigator, might cause this study to be detrimental to the patient. * Medication-related: * Ultraviolet B (UVB) therapy, topical steroids, topical calcineurin inhibitors, topical Vitamin A or D analog preparations, or anthralin within 14 days of baseline. Exceptions: low potency topical corticosteroids (class I and II, according to European classification for potency of topical corticosteroids) were allowed as therapy for the face, groin, axillae in accordance with the manufacturer's suggested usage dose * Psoralen plus ultraviolet A radiation (PUVA), ciclosporin, acitretin, alitretinoin, alefacept (Amevive®), anakinra (Kineret®), systemic corticosteroids, methotrexate, fumaric acids or any other systemic anti- psoriasis therapy within 28 days of baseline * Prior (within the last 2 years) or concomitant use of antipsoriatic biologic therapy with TNF-alpha blocker and/or ustekinumab and/or ixekizumab and/or secukinumab and/or brodalumab and/or guselkumab * Concomitant use of strong cytochrome P450 3A4 (CYP3A4) enzyme inductors (e.g. rifampicin, phenobarbital, carbamazepin, phenytoin and St. John's wort) * Use of an investigational drug within 4 weeks prior to baseline or 5 pharmacokinetic/pharmacodynamics half-lives (whichever is longer) * Prior treatment with apremilast/Otezla® * Receipt of any live (attenuated) vaccine within 28 days prior to baseline * Concomitant use of any other PDE4 inhibitor * Patients with hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption * For patients with skin biopsy samples taken: patients with clinically relevant coagulation disorders or medication or known hypersensitivity against local anesthetics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | PPPASI Score at baseline and Week 20. | The PPPASI assess palms of hands and soles of feet for psoriasis involvement. The PPPASI score range from 0-72, with higher scores indicating more severe disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With PPPASI 50 Response | At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20). | PPPASI 50 response defined as a 50% decrease in PPPASI from baseline. |
| Number of Participants With PPPASI 75 Response | At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20). | PPPASI 75 response defined as a 75% decrease in PPPASI from baseline. |
| Dermatology Life Quality Index (DLQI) | At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20). | The DLQI is a dermatology-specific quality of life instrument designed to assess the impact of a disease on the patient's daily life which is also validated for PPP. It is a 10-item questionnaire and can be used to assess 6 different aspects: symptoms and feelings, leisure, daily activities, work or school performance, personal relationship and treatment. The DLQI was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life was impaired. Meaning of DLQI scores: * 0 to 1 = No effect at all on patient's life * 2 to 5 = Small effect on patient's life * 6 to 10 = Moderate effect on patient's life * 11 to 20 = Very large effect on patient's life * 21 to 30 = Extremely large effect on patient's life |
Other
| Measure | Time frame | Description |
|---|---|---|
| Visual Analogue Scale (VAS) Pruritus/Itch | At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20). | VAS was used to assess pruritus/itch. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (at 0 mm) represented no pruritus/itch, and the right-hand boundary (at 100 mm) represented pruritus/itch as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more pruritus/itch (worse outcomes). |
| Hand and Feet Physician Global Assessment (H&F PGA) | At Visit 2 (Baseline), Visit 3 (Week 4) , Visit 4 (Week 12) and Visit 5 (Week 20). | The H&F PGA describes the severity of psoriasis on the hands and/or feet using five categories ranging from 0 (clear) to 4 (severe). |
| Dynamic H&F PGA | At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20). | The dynamic H&F PGA describes the global improvement compared with baseline. It relies on the physician's memory of the baseline severity to evaluate the level of alteration. The categories vary between 0 (cleared) and 6 (worse). |
| Psoriasis Area and Severity Index (PASI) | At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20). | The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. |
| Pustules Count Percent Change From Baseline | At Visit 2 (Baseline) and Visit 5 (End of Study - Week 20) | Percentage change from baseline in Pustules count after 20 weeks of treatment with Apremilast |
| Number of Participants With Pustules Count 50 and 75 Response | At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study-Week 20). | Patients experiencing a 50% and 75% decrease in Pustules count from baseline |
| Visual Analogue Scale (VAS) Discomfort/Pain | At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20). | VAS was used to assess discomfort/pain. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary represented no discomfort/pain (at 0 mm), and the right-hand boundary (at 100 mm) represented discomfort/pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more discomfort/pain (worse conditions). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Full Analysis Set (FAS) The full analysis set (FAS) consisted of all patients who received at least one dose of study drug. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Full Analysis Set (FAS) |
|---|---|
| Age at initial diagnosis of PPP | 52.10 years STANDARD_DEVIATION 13.58 |
| Age, Continuous | 59.76 years STANDARD_DEVIATION 9.26 |
| Current involvement of nails No | 11 Participants |
| Current involvement of nails Unknown | 1 Participants |
| Current involvement of nails Yes | 9 Participants |
| Current involvement of scalp No | 20 Participants |
| Current involvement of scalp Yes | 1 Participants |
| Do you suffer from P. vulgaris? No | 15 Participants |
| Do you suffer from P. vulgaris? Yes | 6 Participants |
| Highest educational status Professional School | 5 Participants |
| Highest educational status Secondary school leaving certificate | 14 Participants |
| Highest educational status University degree | 2 Participants |
| Is the patient a smoker? Current smoker | 15 Participants |
| Is the patient a smoker? Ex-smoker | 4 Participants |
| Is the patient a smoker? Non-smoker | 2 Participants |
| Number of involved Fingernails | 1.22 nails |
| Number of involved Toenails | 3.33 nails |
| Plaque Psoriasis No | 15 Participants |
| Plaque Psoriasis Yes | 6 Participants |
| Psoriasis erythrodermica No | 21 Participants |
| Psoriasis erythrodermica Yes | 0 Participants |
| Psoriasis inversa No | 19 Participants |
| Psoriasis inversa Yes | 2 Participants |
| Psoriasis pustulosa generalisata No | 21 Participants |
| Psoriasis pustulosa generalisata Yes | 0 Participants |
| Psoriatic arthritis No | 18 Participants |
| Psoriatic arthritis Yes | 3 Participants |
| Race/Ethnicity, Customized Race Other (Sinti) | 1 Participants |
| Race/Ethnicity, Customized Race White | 20 Participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 19 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline
The PPPASI assess palms of hands and soles of feet for psoriasis involvement. The PPPASI score range from 0-72, with higher scores indicating more severe disease.
Time frame: PPPASI Score at baseline and Week 20.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Full Analysis Set (FAS) | Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | Visit 2 - Baseline | 16.50 PPPASI Score |
| Full Analysis Set (FAS) | Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | Visit 5 - End of Study - Week 20 | 7.65 PPPASI Score |
| Per Protocol Set (PPS) | Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | Visit 2 - Baseline | 15.85 PPPASI Score |
| Per Protocol Set (PPS) | Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | Visit 5 - End of Study - Week 20 | 7.65 PPPASI Score |
| Full Analysis Set - LOCF | Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | Visit 2 - Baseline | 16.50 PPPASI Score |
| Full Analysis Set - LOCF | Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline | Visit 5 - End of Study - Week 20 | 8.10 PPPASI Score |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
Dermatology Life Quality Index (DLQI)
The DLQI is a dermatology-specific quality of life instrument designed to assess the impact of a disease on the patient's daily life which is also validated for PPP. It is a 10-item questionnaire and can be used to assess 6 different aspects: symptoms and feelings, leisure, daily activities, work or school performance, personal relationship and treatment. The DLQI was calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life was impaired. Meaning of DLQI scores: * 0 to 1 = No effect at all on patient's life * 2 to 5 = Small effect on patient's life * 6 to 10 = Moderate effect on patient's life * 11 to 20 = Very large effect on patient's life * 21 to 30 = Extremely large effect on patient's life
Time frame: At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20).
Population: The number analyzed in one or more rows differs from the overall number of patients included in the FAS or PPS population as DLQI score was not available for all patients at all timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Full Analysis Set (FAS) | Dermatology Life Quality Index (DLQI) | Visit 2 - Baseline | 8.50 DLQI Score |
| Full Analysis Set (FAS) | Dermatology Life Quality Index (DLQI) | Visit 4 - Week 12 | 2.50 DLQI Score |
| Full Analysis Set (FAS) | Dermatology Life Quality Index (DLQI) | Visit 5 - End of Study - Week 20 | 2.00 DLQI Score |
| Per Protocol Set (PPS) | Dermatology Life Quality Index (DLQI) | Visit 2 - Baseline | 8.00 DLQI Score |
| Per Protocol Set (PPS) | Dermatology Life Quality Index (DLQI) | Visit 4 - Week 12 | 2.50 DLQI Score |
| Per Protocol Set (PPS) | Dermatology Life Quality Index (DLQI) | Visit 5 - End of Study - Week 20 | 2.00 DLQI Score |
Secondary
Number of Participants With PPPASI 50 Response
PPPASI 50 response defined as a 50% decrease in PPPASI from baseline.
Time frame: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Full Analysis Set (FAS) | Number of Participants With PPPASI 50 Response | Visit 3 - Week 4 | 7 Participants |
| Full Analysis Set (FAS) | Number of Participants With PPPASI 50 Response | Visit 4 - Week 12 | 12 Participants |
| Full Analysis Set (FAS) | Number of Participants With PPPASI 50 Response | Visit 5 - End of Study - Week 20 | 13 Participants |
| Per Protocol Set (PPS) | Number of Participants With PPPASI 50 Response | Visit 3 - Week 4 | 7 Participants |
| Per Protocol Set (PPS) | Number of Participants With PPPASI 50 Response | Visit 4 - Week 12 | 12 Participants |
| Per Protocol Set (PPS) | Number of Participants With PPPASI 50 Response | Visit 5 - End of Study - Week 20 | 13 Participants |
Secondary
Number of Participants With PPPASI 75 Response
PPPASI 75 response defined as a 75% decrease in PPPASI from baseline.
Time frame: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Full Analysis Set (FAS) | Number of Participants With PPPASI 75 Response | Visit 5 - End of Study - Week 20 | 3 Participants |
| Full Analysis Set (FAS) | Number of Participants With PPPASI 75 Response | Visit 3 - Week 4 | 2 Participants |
| Full Analysis Set (FAS) | Number of Participants With PPPASI 75 Response | Visit 4 - Week 12 | 6 Participants |
| Per Protocol Set (PPS) | Number of Participants With PPPASI 75 Response | Visit 3 - Week 4 | 2 Participants |
| Per Protocol Set (PPS) | Number of Participants With PPPASI 75 Response | Visit 4 - Week 12 | 6 Participants |
| Per Protocol Set (PPS) | Number of Participants With PPPASI 75 Response | Visit 5 - End of Study - Week 20 | 3 Participants |
Other Pre-specified
Dynamic H&F PGA
The dynamic H&F PGA describes the global improvement compared with baseline. It relies on the physician's memory of the baseline severity to evaluate the level of alteration. The categories vary between 0 (cleared) and 6 (worse).
Time frame: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 5 fair | 7 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 0 cleared | 0 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 1 excellent | 2 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 0 cleared | 0 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 2 good | 4 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 3 slight | 3 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 4 unchanged | 4 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 3 - Week 4 | 6 worse | 0 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 0 cleared | 0 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 1 excellent | 5 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 2 good | 5 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 3 slight | 2 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 4 unchanged | 2 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 5 fair | 6 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 4 - Week 12 | 6 worse | 0 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 1 excellent | 5 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 2 good | 7 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 3 slight | 2 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 4 unchanged | 2 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 5 fair | 4 Participants |
| Full Analysis Set (FAS) | Dynamic H&F PGA | Visit 5 - End of Study - Week 20 | 6 worse | 0 Participants |
Other Pre-specified
Hand and Feet Physician Global Assessment (H&F PGA)
The H&F PGA describes the severity of psoriasis on the hands and/or feet using five categories ranging from 0 (clear) to 4 (severe).
Time frame: At Visit 2 (Baseline), Visit 3 (Week 4) , Visit 4 (Week 12) and Visit 5 (Week 20).
Population: In the FAS 20 participants were analyzed in all visits, except at Visit 2 (n=21).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 0 clear | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 1 almost clear | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 2 mild | 2 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 3 moderate | 19 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 4 severe | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 0 clear | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 1 almost clear | 1 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 2 mild | 10 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 3 moderate | 9 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 4 severe | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 0 clear | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 1 almost clear | 3 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 2 mild | 9 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 3 moderate | 8 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 4 severe | 0 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 0 clear | 1 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 1 almost clear | 1 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 2 mild | 10 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 3 moderate | 8 Participants |
| Full Analysis Set (FAS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 4 severe | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 2 mild | 10 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 0 clear | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 0 clear | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 1 almost clear | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 0 clear | 1 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 2 mild | 2 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 1 almost clear | 3 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 3 moderate | 18 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 4 severe | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 2 - Baseline | 4 severe | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 2 mild | 9 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 0 clear | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 1 almost clear | 1 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 1 almost clear | 1 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 3 moderate | 8 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 2 mild | 10 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 5 - End of Study - Week 20 | 3 moderate | 8 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 3 moderate | 9 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 4 - Week 12 | 4 severe | 0 Participants |
| Per Protocol Set (PPS) | Hand and Feet Physician Global Assessment (H&F PGA) | Visit 3 - Week 4 | 4 severe | 0 Participants |
Other Pre-specified
Number of Participants With Pustules Count 50 and 75 Response
Patients experiencing a 50% and 75% decrease in Pustules count from baseline
Time frame: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study-Week 20).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Full Analysis Set (FAS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 50: Visit 3 - Week 4 | 13 Participants |
| Full Analysis Set (FAS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 50: Visit 4 - Week 12 | 18 Participants |
| Full Analysis Set (FAS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 50: Visit 5-End of Study- Week 20 | 16 Participants |
| Full Analysis Set (FAS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 75: Visit 3 - Week 4 | 8 Participants |
| Full Analysis Set (FAS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 75: Visit 4 - Week 12 | 14 Participants |
| Full Analysis Set (FAS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 75: Visit 5-End of Study- Week 20 | 12 Participants |
| Per Protocol Set (PPS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 75: Visit 4 - Week 12 | 14 Participants |
| Per Protocol Set (PPS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 50: Visit 3 - Week 4 | 14 Participants |
| Per Protocol Set (PPS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 75: Visit 3 - Week 4 | 9 Participants |
| Per Protocol Set (PPS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 50: Visit 4 - Week 12 | 17 Participants |
| Per Protocol Set (PPS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 75: Visit 5-End of Study- Week 20 | 12 Participants |
| Per Protocol Set (PPS) | Number of Participants With Pustules Count 50 and 75 Response | Pustules count 50: Visit 5-End of Study- Week 20 | 16 Participants |
Other Pre-specified
Psoriasis Area and Severity Index (PASI)
The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score.
Time frame: At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
Population: PASI score was available only for 6 patients included in the PPS population at all assessment times.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Full Analysis Set (FAS) | Psoriasis Area and Severity Index (PASI) | Visit 2 - Baseline | 3.85 PASI Score |
| Full Analysis Set (FAS) | Psoriasis Area and Severity Index (PASI) | Visit 3 - Week 4 | 2.27 PASI Score |
| Full Analysis Set (FAS) | Psoriasis Area and Severity Index (PASI) | Visit 4 - Week 12 | 0.5 PASI Score |
| Full Analysis Set (FAS) | Psoriasis Area and Severity Index (PASI) | Visit 5-End of Study-Week 20 | 0.95 PASI Score |
Other Pre-specified
Pustules Count Percent Change From Baseline
Percentage change from baseline in Pustules count after 20 weeks of treatment with Apremilast
Time frame: At Visit 2 (Baseline) and Visit 5 (End of Study - Week 20)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Full Analysis Set (FAS) | Pustules Count Percent Change From Baseline | -76.3 Percent change |
| Per Protocol Set (PPS) | Pustules Count Percent Change From Baseline | -79.82 Percent change |
p-value: <0.001Wilcoxon Signed-rank test
Other Pre-specified
Visual Analogue Scale (VAS) Discomfort/Pain
VAS was used to assess discomfort/pain. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary represented no discomfort/pain (at 0 mm), and the right-hand boundary (at 100 mm) represented discomfort/pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more discomfort/pain (worse conditions).
Time frame: At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 2 - Baseline | 44.0 Units on a scale |
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 3 - Week 4 | 4.0 Units on a scale |
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 4 - Week 12 | 2.0 Units on a scale |
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 5 - End of Study - Week 20 | 9.0 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 5 - End of Study - Week 20 | 7.5 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 2 - Baseline | 37.5 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 4 - Week 12 | 1.5 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Discomfort/Pain | Visit 3 - Week 4 | 3.0 Units on a scale |
Other Pre-specified
Visual Analogue Scale (VAS) Pruritus/Itch
VAS was used to assess pruritus/itch. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (at 0 mm) represented no pruritus/itch, and the right-hand boundary (at 100 mm) represented pruritus/itch as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more pruritus/itch (worse outcomes).
Time frame: At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 2 - Baseline | 31.0 Units on a scale |
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 3 - Week 4 | 2.0 Units on a scale |
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 4 - Week 12 | 25.0 Units on a scale |
| Full Analysis Set (FAS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 5 - End of Study - Week 20 | 12.0 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 5 - End of Study - Week 20 | 11.5 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 2 - Baseline | 29.5 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 4 - Week 12 | 24.0 Units on a scale |
| Per Protocol Set (PPS) | Visual Analogue Scale (VAS) Pruritus/Itch | Visit 3 - Week 4 | 11.0 Units on a scale |