Palmoplantar PustulosisPhase 2APLANTUSNCT04572997
Apremilast in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP) (APLANTUS)
A Phase 2 study testing Apremilast in people with Palmoplantar Pustulosis, run by Kristian Reich at 5 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Palmoplantar Pustulosis
- What is being tested?
- Apremilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 5 sitesGermany
- Study dates
- 29 Nov 2018to 29 Aug 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 12Show fewer
- 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).
Who cannot join
- 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
Show all 37Show fewer
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites
University Hospital Bonn
Bonn, 53127
Universitätsmedizin Göttingen / Georg-August-Universität Department for Dermatology, Venereology and Allergology
Göttingen, 37075
SCIderm GmbH
Harburg, 20354
Universitätsklinik Schleswig-Holstein, Campus Kiel, PSORIASIS-ZENTRUM KIEL, Klinik für Dermatologie, Venerologie und Allergologie
Kiel, 24105
Universitätsklinikum Münster Klinik für Hautkrankheiten
Münster, 48149
About this study
Official title: A Multicenter, Open Label, Single-arm Pilot Study to Evaluate the Efficacy and Safety of Oral Apremilast in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP) (APLANTUS)
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.
Read the 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.
- Conditions
- Palmoplantar Pustulosis
- Being tested
- Apremilast
- Keywords
- PPP, Palmoplantar Pustulosis, Apremilast, Otezla
- Medical subject headings
- Psoriasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApremilastDrug
Also called Otezla®
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.
| Study group | Role | What they receive |
|---|---|---|
| Full analysis set (FAS) | Experimental | The full analysis set (FAS) consisted of all patients who received at least one dose of study drug. Receives: Drug: Apremilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: PPPASI Score at baseline and Week 20.
Secondary outcomes (3)
Number of Participants With PPPASI 50 Response
PPPASI 50 response defined as a 50% decrease in PPPASI from baseline.
Measured: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
Number of Participants With PPPASI 75 Response
PPPASI 75 response defined as a 75% decrease in PPPASI from baseline.
Measured: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
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
Measured: At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2020
- Study start29 Nov 2018
- Primary completion29 Aug 2019
- Study completion29 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Palmoplantar PustulosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This was an open-label, single-arm, pilot study to evaluate the efficacy and safety of apremilast.
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kristian Reich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Kristian Reich, Universitätsklinikum Hamburg-Eppendorf
- Investigators
- Kristian Reich, MD, PhD, Study chair, Prof. Dr. Kristian Reich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04572997
- Sponsor's protocol ID
- 069-008.
- Other IDs
- 2016-005122-11, 2016
- Acronym
- APLANTUS
- Status last verified
- Sep 2021
- First submitted
- 21 Sep 2020
- Last updated
- 24 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34077577
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open Label, Single-arm Pilot Study to Evaluate the Efficacy and Safety of Oral Apremilast in Patients With Moderate to Severe Palmoplantar Pustulosis (PPP) (APLANTUS)
- ClinicalTrials.gov ID
- NCT04572997
- Acronym / sponsor ID
- APLANTUS / 069-008.
- Conditions
- Palmoplantar Pustulosis
- Keywords
- PPP, Palmoplantar Pustulosis, Apremilast, Otezla
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Kristian ReichUniversity, hospital or other
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 29 Aug 2019 (actual)
- Study completion
- 29 Aug 2019 (actual)
- First posted
- 5 Oct 2020 (actual)
- Results
- Posted 24 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This was an open-label, single-arm, pilot study to evaluate the efficacy and safety of apremilast.
| Arm | Type | Receives |
|---|---|---|
| Full analysis set (FAS) | Experimental | Drug: ApremilastThe full analysis set (FAS) consisted of all patients who received at least one dose of study drug. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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:
Key exclusion criteria (37 listed)
- General:
- Disease-related:
- Medication-related:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApremilastAlso: Otezla®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. | Drug | Full analysis set (FAS) |
Primary outcome
Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline
Time frame: 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.
3 secondary outcomes
Number of Participants With PPPASI 50 Response
Time frame: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
Number of Participants With PPPASI 75 Response
Time frame: At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).
Dermatology Life Quality Index (DLQI)
Time frame: At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 34077577Wilsmann-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.
- Individual participant dataSharing planned: No
Related trials for Palmoplantar Pustulosis
Not yet recruitingPhase 2
A Trial Evaluating the Efficacy and Safety of SHR-1139 Injection in Adult Patients With Palmoplantar Pustulosis
Palmoplantar Pustulosis of Adults
RecruitingObservational study
Collection of Samples From Subjects With Various Skin Conditions and Healthy Volunteers
Acne, Atopic Dermatitis
RecruitingPhase 2
A 16-week Trial to Investigate the Efficacy and Safety of Delgocitinib Cream 20 mg/g in Adult Participants With Mild to Severe Palmoplantar Pustulosis
Palmoplantar Pustulosis
Active, not recruitingObservational study
A Study Comparing the Risk of Serious Infections and Malignancies With Deucravacitinib or Biologics in Japanese Patients With Psoriasis
Psoriasis
Active, not recruitingPhase 3
A Study of JNJ-77242113 for the Treatment of Participants With Generalized Pustular Psoriasis or Erythrodermic Psoriasis
Generalized Pustular Psoriasis, Erythrodermic Psoriasis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kristian Reich, MD, PhD study chair
Prof. Dr. Kristian Reich
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apremilast in people with Palmoplantar Pustulosis, run by Kristian Reich at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline (time frame: PPPASI Score at baseline and Week 20.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04572997, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2021.