Palmoplantar pustulosis (PPP)
Conditions
Interventions
Trade Name: Otezla®
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Apremilast
CAS Number: 608141-41-9
Other descriptive name: APREMILAST
Concentration unit: mg milligram(s)
Concentration
Sponsors
Prof. Dr. Kristian Reich
Eligibility
Sex/Gender
All
Inclusion criteria
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 are 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 are 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 highly effective contraceptive measures from Screeing visit until the end of at least one menstrual cycle (but not less than 28 days) following discontinuation of apremilast as defined below: - Females 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 post-menopausal) - Male patient, and his 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 is 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 are involved in the organization of the study -Patients who are in any way dependent on the investigator -Patients who are 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/1.73 m2 according to the 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 HIV test result, hepatitis B surface (HBS) antigen or hepatitis C (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) will be 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 are 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 hypersen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate a significant improvement of Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at week 20 compared with baseline in moderate to severe chronic palmoplantar pustulosis under apremilast therapy.;Secondary Objective: -To evaluate an improvement of PPPASI at all assessment times compared with baseline in moderate to severe chronic palmoplantar pustulosis under apremilast therapy. -To evaluate differences during the treatment with apremilast in life quality assessment measures: Dermatology Life Quality Index (DLQI) at all assessment times compared with baseline -To evaluate safety of apremilast in patients with moderate to severe palmoplantar pustulosis;Primary end point(s): Percentage change from baseline in PPPASI after 20 weeks of treatment with apremilast;Timepoint(s) of evaluation of this end point: At screening, baseline and weeks 4, 12 and 20. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Absolute and percent change from baseline in PPPASI during the 20 weeks treatment period -PPPASI 50 response and PPPASI 75 response, defined as a 50% and 75% decrease in PPPASI from baseline, during the 20 weeks treatment period -DLQI bands (0-1 no effect, 2-5 small effect, 6-10 moderate effect, 11-20 very large effect, 21-30 extremely large effect) during the 20 weeks treatment period -Absolute and percent change from baseline in DLQI during the 20 weeks treatment period - Safety as assessed by AEs, vital signs and physical examination;Timepoint(s) of evaluation of this end point: -PPASI at screening, baseline and weeks 4, 12 and 20. -DLQI at baseline, week 12 and 20. | — |
Countries
Germany
Contacts
Public ContactProf. Dr. Kristian Reich
Prof. Dr. Kristian Reich
Outcome results
None listed