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NCT04572997: APLANTUS

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

Completed Phase 2 Results posted Last updated 24 September 2021
What this trial tests

Phase 2 trial testing Apremilast in Palmoplantar Pustulosis in 21 participants. Completed in 29 August 2019.

Timeline
29 November 2018
Primary endpoint
29 August 2019
29 August 2019

Quick facts

Lead sponsorKristian Reich
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment21
Start date29 November 2018
Primary completion29 August 2019
Estimated completion29 August 2019
Sites5 locations across Germany

Drugs / interventions tested

Conditions studied

Sponsor

Kristian Reich

Who can join

18 and older, any sex, with Palmoplantar Pustulosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Palmoplantar Pustulosis Psoriasis Area and Severity Index (PPPASI) at Week 20 Compared With Baseline Primary · 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.

Visit 2 - Baseline
GroupValue95% CI
Full Analysis Set (FAS)16.5014.00 – 19.50
Per Protocol Set (PPS)15.8513.95 – 19.85
Full Analysis Set - LOCF16.5014.00 – 19.50
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)7.654.45 – 10.6
Per Protocol Set (PPS)7.654.45 – 10.60
Full Analysis Set - LOCF8.104.50 – 11.20
Number of Participants With PPPASI 50 Response Secondary · At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).

PPPASI 50 response defined as a 50% decrease in PPPASI from baseline.

Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)7
Per Protocol Set (PPS)7
Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)12
Per Protocol Set (PPS)12
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)13
Per Protocol Set (PPS)13
Number of Participants With PPPASI 75 Response Secondary · At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (Week 20).

PPPASI 75 response defined as a 75% decrease in PPPASI from baseline.

Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)2
Per Protocol Set (PPS)2
Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)6
Per Protocol Set (PPS)6
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)3
Per Protocol Set (PPS)3
Dermatology Life Quality Index (DLQI) Secondary · At Visit 2 (Baseline), Visit 4 (Week 12) and Visit 5 (Week 20).

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 lif

Visit 2 - Baseline
GroupValue95% CI
Full Analysis Set (FAS)8.505.00 – 15.50
Per Protocol Set (PPS)8.005.00 – 16.00
Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)2.501.00 – 10.50
Per Protocol Set (PPS)2.501.00 – 10.50
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)2.001.00 – 13.00
Per Protocol Set (PPS)2.001.00 – 13.00
Hand and Feet Physician Global Assessment (H&F PGA) Secondary · At Visit 2 (Baseline), Visit 3 (Week 4) , Visit 4 (Week 12) and Visit 5 (Week 20).

The H\&F PGA describes the severity of psoriasis on the hands and/or feet using five categories ranging from 0 (clear) to 4 (severe).

Visit 2 - Baseline
GroupValue95% CI
Full Analysis Set (FAS)0
Per Protocol Set (PPS)0
Full Analysis Set (FAS)0
Per Protocol Set (PPS)0
Full Analysis Set (FAS)2
Per Protocol Set (PPS)2
Full Analysis Set (FAS)19
Per Protocol Set (PPS)18
Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)0
Per Protocol Set (PPS)0
Full Analysis Set (FAS)1
Per Protocol Set (PPS)1
Full Analysis Set (FAS)10
Per Protocol Set (PPS)10
Full Analysis Set (FAS)9
Per Protocol Set (PPS)9
Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)0
Per Protocol Set (PPS)0
Full Analysis Set (FAS)3
Per Protocol Set (PPS)3
Full Analysis Set (FAS)9
Per Protocol Set (PPS)9
Full Analysis Set (FAS)8
Per Protocol Set (PPS)8
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)1
Per Protocol Set (PPS)1
Full Analysis Set (FAS)1
Per Protocol Set (PPS)1
Full Analysis Set (FAS)10
Per Protocol Set (PPS)10
Full Analysis Set (FAS)8
Per Protocol Set (PPS)8
Pustules Count Percent Change From Baseline Secondary · At Visit 2 (Baseline) and Visit 5 (End of Study - Week 20)

Percentage change from baseline in Pustules count after 20 weeks of treatment with Apremilast

GroupValue95% CI
Full Analysis Set - LOCF-76.3-100 – -53.4
Per Protocol Set (PPS)-79.82-100 – -57.33
Number of Participants With Pustules Count 50 and 75 Response Secondary · At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study-Week 20).

Patients experiencing a 50% and 75% decrease in Pustules count from baseline

Pustules count 50: Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)13
Per Protocol Set (PPS)14
Pustules count 50: Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)18
Per Protocol Set (PPS)17
Pustules count 50: Visit 5-End of Study- Week 20
GroupValue95% CI
Full Analysis Set (FAS)16
Per Protocol Set (PPS)16
Pustules count 75: Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)8
Per Protocol Set (PPS)9
Pustules count 75: Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)14
Per Protocol Set (PPS)14
Pustules count 75: Visit 5-End of Study- Week 20
GroupValue95% CI
Full Analysis Set (FAS)12
Per Protocol Set (PPS)12
Visual Analogue Scale (VAS) Discomfort/Pain Secondary · At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).

VAS was used to assess discomfort/pain. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary represented no discomfort/pain (at 0 mm), and the right-hand boundary (at 100 mm) represented discomfort/pain as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more discomfort/pain (worse conditions).

Visit 2 - Baseline
GroupValue95% CI
Full Analysis Set (FAS)44.011.0 – 67.0
Per Protocol Set (PPS)37.59.0 – 61.0
Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)4.00.0 – 19.0
Per Protocol Set (PPS)3.00.0 – 19.0
Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)2.00.0 – 27.0
Per Protocol Set (PPS)1.50.0 – 21.0
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)9.03.0 – 61.0
Per Protocol Set (PPS)7.52.5 – 29.5
Visual Analogue Scale (VAS) Pruritus/Itch Secondary · At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).

VAS was used to assess pruritus/itch. The patient was asked to place a vertical stroke on a 100 mm VAS on which the left-hand boundary (at 0 mm) represented no pruritus/itch, and the right-hand boundary (at 100 mm) represented pruritus/itch as severe as can be imagined. The distance from the mark to the left-hand boundary was recorded, with higher values indicating more pruritus/itch (worse outcomes).

Visit 2 - Baseline
GroupValue95% CI
Full Analysis Set (FAS)31.016.0 – 55.0
Per Protocol Set (PPS)29.512.5 – 49.0
Visit 3 - Week 4
GroupValue95% CI
Full Analysis Set (FAS)2.02.0 – 48.0
Per Protocol Set (PPS)11.02.0 – 39.75
Visit 4 - Week 12
GroupValue95% CI
Full Analysis Set (FAS)25.04.0 – 44.0
Per Protocol Set (PPS)24.03.5 – 37.25
Visit 5 - End of Study - Week 20
GroupValue95% CI
Full Analysis Set (FAS)12.06.0 – 49.0
Per Protocol Set (PPS)11.55.25 – 30.25
Psoriasis Area and Severity Index (PASI) Secondary · At Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).

The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

Visit 2 - Baseline
GroupValue95% CI
Per Protocol Set (PPS)3.851.93 – 5.18
Visit 3 - Week 4
GroupValue95% CI
Per Protocol Set (PPS)2.270.3 – 3.65
Visit 4 - Week 12
GroupValue95% CI
Per Protocol Set (PPS)0.50.0 – 2.35
Visit 5-End of Study-Week 20
GroupValue95% CI
Per Protocol Set (PPS)0.950.0 – 2.28
Dynamic H&F PGA Secondary · At Visit 3 (Week 4), Visit 4 (Week 12) and Visit 5 (End of Study - Week 20).

The dynamic H\&F PGA describes the global improvement compared with baseline. It relies on the physician's memory of the baseline severity to evaluate the level of alteration. The categories vary between 0 (cleared) and 6 (worse).

Visit 3 - Week 4
GroupValue95% CI
Per Protocol Set (PPS)0
Per Protocol Set (PPS)2
Per Protocol Set (PPS)4
Per Protocol Set (PPS)3
Visit 4 - Week 12
GroupValue95% CI
Per Protocol Set (PPS)0
Per Protocol Set (PPS)5
Per Protocol Set (PPS)5
Per Protocol Set (PPS)2
Visit 5 - End of Study - Week 20
GroupValue95% CI
Per Protocol Set (PPS)0
Per Protocol Set (PPS)5
Per Protocol Set (PPS)7
Per Protocol Set (PPS)2

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs were monitored/assessed from baseline (Visit 2, onset of treatment) until the patient's last study visit (i.e., up to 20 weeks). All SAEs were monitored/assessed upon ICF signature (Visit 1) until 30 days after the patient had stopped study participation (i.e., up to 24 weeks plus 30 days).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Full Analysis Set (FAS)
Serious: 0/21 (0%)
Deaths: 0/21
Other adverse events (37 terms — click to expand)

ReactionSystemFull Analysis Set (FAS)
NauseaGastrointestinal disorders
HeadacheNervous system disorders
DiarrhoeaGastrointestinal disorders
NasopharyngitisInfections and infestations
Arthropod biteInjury, poisoning and procedural complications
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Post procedural swellingInjury, poisoning and procedural complications
Ligament sprainInjury, poisoning and procedural complications
Artificial crown procedureSurgical and medical procedures
Endodontic procedureSurgical and medical procedures
TachycardiaCardiac disorders
Nasal drynessRespiratory, thoracic and mediastinal disorders
Nerve compressionNervous system disorders
Tension headacheNervous system disorders
Chest discomfortGeneral disorders
Anxiety disorderPsychiatric disorders
EpulisGastrointestinal disorders
FlatulenceGastrointestinal disorders
GastritisGastrointestinal disorders
ToothacheGastrointestinal disorders
VomitingGastrointestinal disorders
Actinic keratosisSkin and subcutaneous tissue disorders
DermatitisSkin and subcutaneous tissue disorders
EczemaSkin and subcutaneous tissue disorders
HyperkeratosisSkin and subcutaneous tissue disorders
Back painMusculoskeletal and connective tissue disorders
ExostosisMusculoskeletal and connective tissue disorders
Intervertebral disc disorderMusculoskeletal and connective tissue disorders
Limb discomfortMusculoskeletal and connective tissue disorders
TendonitisMusculoskeletal and connective tissue disorders
CystitisInfections and infestations
Gastrointestinal infectionInfections and infestations
InfluenzaInfections and infestations
Respiratory tract infectionInfections and infestations
SinusitisInfections and infestations
Urinary tract infectionInfections and infestations

Data from ClinicalTrials.gov NCT04572997 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. An Overview of PDE4 Inhibitors in Clinical Trials: 2010 to Early 2022.
    Crocetti L, Floresta G, Cilibrizzi A, Giovannoni MP. · · 2022 · cited 85× · PMID 35956914 · DOI 10.3390/molecules27154964
  2. Pustular Psoriasis: From Pathophysiology to Treatment.
    Genovese G, Moltrasio C, Cassano N, Maronese CA, et al · · 2021 · cited 40× · PMID 34944562 · DOI 10.3390/biomedicines9121746
  3. Exploring the Therapeutic Landscape: A Narrative Review on Topical and Oral Phosphodiesterase-4 Inhibitors in Dermatology.
    Carmona-Rocha E, Rusiñol L, Puig L. · · 2025 · cited 11× · PMID 39861739 · DOI 10.3390/pharmaceutics17010091

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