| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Palmoplantar pustulosis (PPP) |
|
| E.1.1.1 | Medical condition in easily understood language |
A chronic disease with erythematous and scaly plaques
studded with sterile pustules on the palms or soles. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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. |
|
| E.2.2 | Secondary objectives of the trial |
-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 |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Exploratory sub-study:
Additional samples will be collected to explore the effect of apremilast on levels of immunological markers in skin samples. The sub-study is optional and a separate Informed Consent form needs to be signed by the patients.
Details on this sub-study will be outlined in a separate document and analysed separately from the main study by the Psoriasis Research and Treatment Center (PRTC, Department of Dermatology and Allergy and Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany). The person responsible for the sub-study is Dr. Robert Sabat, in consultation with the sponsor.
In short, this exploratory research will include analyses of:
-tissue markers in biopsies of lesional skin. |
|
| E.3 | Principal 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). |
|
| E.4 | Principal 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 hypersensitivity against local anesthetics |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Percentage change from baseline in PPPASI after 20 weeks of treatment with
apremilast |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| At screening, baseline and weeks 4, 12 and 20. |
|
| E.5.2 | 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 |
|
| E.5.2.1 | 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. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 0 |
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