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

NCT04572997 | Completed Phase 2 Results

• 2 other identifiers: 069-008.2016-005122-11
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 5

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.

Conditions

Palmoplantar Pustulosis

Keywords

PPP; Palmoplantar Pustulosis; Apremilast; Otezla

Outcome Measures

Primary Outcomes (1)

• 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.

  PPPASI Score at baseline and Week 20.

Secondary Outcomes (3)

• Number of Participants With PPPASI 50 Response

  At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).

• Number of Participants With PPPASI 75 Response

  At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).

• Dermatology Life Quality Index (DLQI)

  At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20).

Other Outcomes (7)

• 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).

• Pustules Count Percent Change From Baseline

  At Visit 2 (Baseline) and Visit 5 (End of Study - Week 20)

• 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).

Study Arms (1)

Full analysis set (FAS)

EXPERIMENTAL

The full analysis set (FAS) consisted of all patients who received at least one dose of study drug.

Drug: Apremilast

Interventions

Apremilast DRUG

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.

Also known as: Otezla®

Full analysis set (FAS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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:

Sponsors & Collaborators

• Kristian Reich: lead

Study Sites (5)

University Hospital Bonn

Bonn, 53127, Germany

Location

Universitätsmedizin Göttingen / Georg-August-Universität Department for Dermatology, Venereology and Allergology

Göttingen, 37075, Germany

Location

SCIderm GmbH

Harburg, 20354, Germany

Location

Universitätsklinik Schleswig-Holstein, Campus Kiel, PSORIASIS-ZENTRUM KIEL, Klinik für Dermatologie, Venerologie und Allergologie

Kiel, 24105, Germany

Location

Universitätsklinikum Münster Klinik für Hautkrankheiten

Münster, 48149, Germany

Location

Related Publications (1)

• Wilsmann-Theis D, Kromer C, Gerdes S, Linker C, Magnolo N, Sabat R, Reich K, Mossner R. A multicentre open-label study of apremilast in palmoplantar pustulosis (APLANTUS). J Eur Acad Dermatol Venereol. 2021 Oct;35(10):2045-2050. doi: 10.1111/jdv.17441. Epub 2021 Jun 24.

  PMID: 34077577 RESULT

MeSH Terms

Conditions

Psoriasis

Interventions

apremilast

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The interpretation of APLANTUS study is limited by the short-term 20-week treatment period and the size of the population.

Results Point of Contact

• Title: Prof. Dr. Kristian Reich
• Organization: Prof. Dr. Kristian Reich

kreich@jerucon.com

+49 1722701941

Study Officials

• Kristian Reich, MD, PhD

  Prof. Dr. Kristian Reich

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Doctor (Prof. Dr.)

Model Details: This was an open-label, single-arm, pilot study to evaluate the efficacy and safety of apremilast.

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: October 5, 2020
• Study Start: November 29, 2018
• Primary Completion: August 29, 2019
• Study Completion: August 29, 2019
• Last Updated: September 24, 2021
• Results First Posted: September 24, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)