Palmoplantar pustulosis Skin and Connective Tissue Diseases
Conditions
Interventions
This is a single-arm study in which all participants will receive the oral JAK inhibitor updacitinib 30 mg once a day for 8 weeks. In certain patient cohorts, outlined in Section 4.4. of the SmPC, the
Sponsors
King's College London
Guy's and St Thomas' NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Investigational Trial: 1. Adults (aged 18 years and over) with a diagnosis of palmoplantar pustulosis* (PPP) made by a trained dermatologist with disease of sufficient impact and severity to require systemic therapy 2. Disease duration of >6 months, not responding to an adequate trial of topical therapy including very potent corticosteroids 3. Evidence of active pustulation on palms and/or soles to ensure sufficient baseline disease activity to detect efficacy 4. At least moderate disease based on a PalmoPlantar Pustulosis Investigator Global Assessment (PPP-IGA) 5. Who have given written, informed consent to participate 6. Willing and able to comply with scheduled visits, treatment plans, laboratory tests and other study procedures *Different forms of psoriasis can co-present together (e.g. chronic plaque psoriasis, Acrodermatitis of Hallopeau, generalised pustular psoriasis). A concomitant diagnosis of a different type of psoriasis will not be a contra-indication to eligibility. Integrated Qualitative Study: Trial Participants and Trial Decliners: 1. Must be eligible for enrolment in the clinical trial aspect of the study 2. Able to give written informed consent to participate Healthcare Professionals: 1. Involved in the recruitment and delivery of the trial 2. Able to give written informed consent to participate
Exclusion criteria
Exclusion criteria: Main Investigational Trial: 1. A history of malignancy of any organ system (other than treated, localised non-melanoma skin cancer), treated or untreated, within the past 5 years 2. With a known history of provoked or unprovoked venous thrombo-embolism (deep vein thrombosis or pulmonary embolism), unless actively treated with long-term anticoagulation 3. Previous treatment with a JAK inhibitor 4. A history of recurrent bacterial, fungal or viral infections which, in the opinion of the principal investigator, present a risk to the patient 5. Evidence of active infection or untreated latent TB 6. HIV positive 7. Active or untreated Hepatitis B or C 8. Use of therapies with potential or known efficacy in psoriasis during or within the following specified timeframe before treatment initiation as listed in the washout section (section 8.6.1) 9. With moderate renal impairment [CrCl 2 x ULN at baseline. Patients who fail this screening criterion may still be considered following review by a hepatologist and confirmed expert opinion that study entry is clinically appropriate. 13. Live vaccinations within 3 months prior to the start of study medication, and willing to not have live vaccinations during the trial and up to 3 months following the last dose. 14. Women who are pregnant, breastfeeding or of childbearing potential* not on adequate contraception** 15. Male participants who are not willing to use highly effective methods of contraception** when engaging in sexual activity with a female of childbearing potential 16. Any condition where, in the opinion of the investigator, the IMP would present risk to the patient. 17. Unable to give written, informed consent. 18. Unable to comply with the study visit schedule. 19. Known hypersensitivity to upadacitinib and/or its excipients (SmPC 6.1) 20. Receipt of any of the following within the specified timeframe before treatment initiation (baseline, visit 1): 20.1. Topical treatments likely to impact signs and symptoms of psoriasis (e.g. potent/very potent corticosteroids, vitamin D analogues, calcineurin inhibitors) within 2 weeks 20.2. Systemic immunosuppressants (e.g. methotrexate, ciclosporin, acitretin) within 4 weeks 20.3. Phototherapy (UVB TL01, UVB, PUVA, UVA1) within 4 weeks 20.4. Etanercept or adalimumab within 4 weeks 20.5. Other biologic therapies (infliximab, certolizumab, ustekinumab, secukinumab, ixekizumab, risankizumab, bimekizumab, brodalumab, tildrakizumab) within 3 months 20.6. Other investigational drugs within 4 months or 5 half-lives (whichever is longer) 20.7. Other immunosuppressant/immunomodulatory therapies including intra-articular steroids within 30 days or 5 half lives (whichever is longer) In line with the Medicines and Healthcare products Regulatory Agency’s (MHRA) recent advice, upadacitinib will only be used in the following cohorts if no suitable treatment alternatives are available: 1. 65 years or older 2. Patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as past long-term smokers) 3. Patients with malignancy risk factors (e.g. current malignancy or history of malignancy) Any decision to treat patients in these cohorts will be made following discussion with the Chief Investigator and will be based on individualised patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Overall proportion of potential participants identified who enrolled in the trial, termed the ‘recruitment rate’ 2. Overall proportion of participants achieving ‘good adherence’ (proportion of days covered >80%) during the trial 3. Overall proportion of participants who view JAK inhibitor therapy in PPP to be ‘acceptable’ Assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Total number of potential participants who have contact with the research team assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) 2. Overall speed of participant identification assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) 3. Overall speed of participant recruitment assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) 4. Total number of ineligible participants assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) 5. Reasons for ineligibility assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) 6. Recruitment of 20 participants assessed at 24 months, or when the recruitment target of 20 participants is achieved (whichever occurs first) 7. Overall mean change in palmoplantar pustulosis psoriasis area and severity index (PP-PASI) over the 8-week treatment period, adjusted for baseline (visit 1) 8. Change in recruitment rate with each phase of the QRI approach assessed at the end of each phase of the QRI approach (new phase for every 20 eligible patient participants approached throughout the trial). | — |
Countries
England, United Kingdom
Contacts
Public ContactDavid Gleeson
Outcome results
None listed