Apremilast as Anti-pruritic Treatment in Patients With Prurigo Nodularis

This study will evaluate the anti-pruritic effect of apremilast in patients with known PN.

Study Overview

• Status: Unknown
• Conditions: Prurigo Nodularis
• Intervention / Treatment: Drug: Apremilast Oral Product

Detailed Description

Prurigo nodularis(PN) is a chronic skin disease, characterized by severe pruritus, multiple hyperkeratotic nodules and papules often located on the extensor part of the upper and lower extremities with a symmetrical distribution. The disease often appears between 20-60 years of age affecting men and women equally.

The pathogenesis of PN is poorly understood and it is unknown whether PN is a primary dermatological disease or if it arises secondary to intense pruritus and scratching of the skin with other diseases being the cause of the itching.

A number of studies have investigated if certain biochemical parameters are involved in mediating PN e.g. studies have indicated that the small nerve fibres in dermis in lesioned skin have an increased density of Substance P (neuropeptide and a well-known mediator of pruritus. when compared to non-lesioned skin.Other studies have suggested that patients with PN have a high presence of nerve growth factor (NGF) in dermis leading to modulation of the small nerve fibres, as well as an increased number of eosinophilic granulocytes, mast- and Merkel cells. Additionally, studies have found increased levels of IL-6 and IL-31 in blood in patient with PN. However the pathogenesis of PN remains unknown.

Among patients with atopic dermatitis there is a higher frequency of patients with PN as well as PN seem to be associated with certain liver- and kidney diseases. Anxiety and depression are also more common in patients with PN.

Patients with PN suffer from impaired quality of life due to ongoing pruritus and skin lesions(5). PN is mainly treated with topical steroids, UVB, PUVA or thalidomide, although none of these treatments seem to be able to control the disease and furthermore a number of these treatments are associated with several side effects.

As the phosphodiesterase 4 (PDE4)-inhibitor (apremilast) have shown a , it is speculated that apremilast may have an effect in patients with PN. Lack of effective treatments for PN supports further development for treatment options.

This study will evaluate the anti-pruritic effect of apremilast in patients with known PN. This interventional study, will be performed at the Department of Dermatology and Allergy at Herlev and Gentofte Hospital (Gentofte site), University of Copenhagen, Hellerup, Denmark.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Hellerup, Denmark, 2900
    • Recruiting
    • Department of Dermato-Allergology
    • Contact: Tanja Todberg, MD; Phone Number: 0045 38673207; Email: tanja.todberg@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• > 18 years of age
• PN verified diagnosis by characteristic clinical features
• Moderate to severe PN
• Failure of local steroid and light treatment to control disease and symptoms.
• Be able to speak and understand Danish.
• Patients must have given their informed consent to the protocol and to the clinical procedures.

Exclusion Criteria:

• Patients who have received any local anti-inflammatory treatment 2 weeks prior to day 0
• Patients who have received any systemic anti-inflammatory treatment 4 weeks prior to day 0 or 5 pharmacokinetic half-lives, whichever is longer
• Patients who have received any other study medication 4 weeks prior to day 0
• Patients with other clinically significant disorders
• Patients with active TB/serious infections
• Any psychiatric condition which in the Investigators opinion would preclude the patient from adhering to the protocol or completing the study per protocol. Patients with previous endogene depression.
• Pregnancy
• Nursing

• Women of child-bearing potential must use effective contraception which includes IUD, oral, injected or implanted hormonal device, hormone patch, vaginal hormonal ring og sterilization.

  • Occlusive cap or condom with spermicidal cream is not considered as an effective contraception. Post-menopausal women (> 12 months of amenorrhea) are allowed not to use contraception.
• Patients who have received any live vaccines 6 weeks prior to day 0 or who are planning to receive a live vaccine during the study
• Allergy to apremilast or any of the other ingredients in Otezla®

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: apremilast; apremilast standard doses	Drug: Apremilast Oral Product; Apremilast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1. Reduction in mean absolute VAS-pruritus score after 12 weeks treatment with apremilast compared to mean VAS-pruritus score before treatment with apremilast	1. Reduction in mean absolute VAS-pruritus score after 12 weeks treatment with apremilast compared to mean VAS-pruritus score before treatment with apremilast	12 weeks

Collaborators and Investigators

• Sponsor: Tanja Todberg, MD

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: June 16, 2017
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 3, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: apremilast
• Additional Relevant MeSH Terms: Skin Diseases; Dermatitis; Skin Diseases, Eczematous; Prurigo; Neurodermatitis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: 2016-003018-29

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No