Apremilast in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP) (APLANTUS)

• Status: Completed
• Trial end date: 2019-08-29
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kristian Reich
• Treatments: Apremilast

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 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.