A Study Examining the Medication Apremilast as Treatment for Chronic Itch

• ClinicalTrials.gov Identifier: NCT03239106
• Recruitment Status: Active, not recruiting
• First Posted: August 3, 2017
• Last Update Posted: September 4, 2019
• Sponsor: Washington University School of Medicine
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

Chronic Itch is a debilitating condition affecting many people. Currently, there are no FDA-approved treatments. Apremilast is an FDA-approved oral medication used to successfully treat the inflammatory skin disorder psoriasis and the inflammatory disorder psoriatic arthritis. This study examines if apremiliast taken twice daily relieves chronic itch.

Condition or disease	Intervention/treatment	Phase
Itch	Drug: Apremilast	Phase 2

Detailed Description:

There is no FDA-approved medication for chronic idiopathic pruritus (CIP). Apremilast has demonstrated notable activity and is approved for treatment in other pruritic inflammatory skin conditions such as psoriasis. The drug is currently being investigated as therapy for atopic dermatitis. Additionally, the investigators have preliminary data to suggest that apremilast's anti-inflammatory properties may work via neuromodulation targeting neuronal cytokine pathways. The proposed study plans to assess the efficacy of apremilast 30 mg BID in the setting of CIP. Durable response to a medication is typically seen within one to two months of starting an efficacious medication in subjects who respond. Therefore, the investigators have designed this study to end at Week 16 to definitively determine efficacy and conclude the study with confidence with regard to both efficacy and failure.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Intervention Model: Single Group Assignment
• Intervention Model Description: open label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Study of Apremilast in Chronic Idiopathic Pruritus
• Actual Study Start Date: December 1, 2017
• Estimated Primary Completion Date: December 31, 2019
• Estimated Study Completion Date: December 31, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: open label; All participants will receive Apremilast 30 mg BID.	Drug: Apremilast; Apremilast 30 mg BID daily; Other Name: Otezla

Outcome Measures

Primary Outcome Measures :

1. Absolute change in NRS itch score form Baseline to Week 16 (end of treatment) [ Time Frame: Baseline and Week 16 ]
   Participants will complete a Numeric Rating Scale for itch ( 0 representing "no itching" through 10 representing "worst itch imaginable") will be recalled from prior 24 hours and the prior week.

Secondary Outcome Measures :

1. Absolute change in DLQI from Baseline to Week 16 [ Time Frame: Baseline and Week 16 ]
   Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16
2. NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18 [ Time Frame: Screening through Week 18 (follow up visit) ]
   Participants' itch will be measured utilizing the Numeric Rating Scale for itch
3. DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18 [ Time Frame: Screening through Week 18 (follow up visit) ]
   Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18.

Other Outcome Measures:

1. Skin RNA-seq (Exploratory endpoint) [ Time Frame: Baseline and Week 16 ]
   Skin biopsies at baseline and Week 16

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Key Inclusion Criteria: A subject who meets all of the following criteria may be included in the study:

• Male and non-pregnant, non-lactating female subjects aged 18 years or older
• Diagnosed with chronic idiopathic pruritus (CIP) with an NRS Itch Score of ≥ 7 at both Screening and Baseline
• Diagnosis of CIP for at least 6 weeks prior to screening
• Willingness to avoid pregnancy or fathering of children
• Ability and willingness to provide written informed consent
• Willing and able to comply with all study requirements and restrictions
• Willing to not participate in any other interventional trial for the duration of their participation
• Subjects must be in good health as determined by medical history, physical examination, electrocardiogram, clinical laboratory tests and vital signs
• Failure of a course 2-week course of treatment with topical triamcinolone 0.1% ointment BID
• Histopathological demonstration of skin eosinophils, mast cell activation, lymphocytic infiltration, and/or dermal edema

Exclusion Criteria:

Key Exclusion Criteria: A subject who meets any of the following criteria will be excluded from the study:

• Chronic pruritus due to a defined primary dermatologic disorder (e.g., atopic dermatitis, psoriasis, etc.)
• Patients with a prior diagnosis of excoriation disorder
• Use of topical treatments for CIP (other than bland emollients) within 1 week of Baseline
• Systemic immunosuppressive or immunomodulating drugs within 4 weeks of Baseline

• Subjects with cytopenias at screening, defined as:

  • Leukocytes < 3 × 109/L.
  • Neutrophils < lower limit of normal.
  • Lymphocytes < 0.5 × 109/L
  • Hemoglobin < 10 g/dL.
  • Platelets < 100 × 109/L.
• Unwilling or unable to follow medication restrictions described in Section 5.6.3, or unwilling or unable to sufficiently washout from use of restricted medication
• Under medical treatment for a skin disease with a therapy listed in the prohibited medications section that may influence the results of the study
• Current clinically significant cardiovascular, respiratory, neurologic, hepatic, hematopoietic, renal gastrointestinal, endocrine or metabolic dysfunction unless currently controlled and stable, including (but not limited to) the following: Positive for Hepatitis C antibody test (anti-HCF) Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) Positive for HIV (DUO test, p24 antigen)
• Active malignancy
• Active substance abuse or history of substance abuse within 6 months of screening
• History (including family history) or current evidence of congenital long QT syndrome or known acquired QT prolongation
• Exposure to any investigational medication, including placebo, within 60 days of the Baseline Visit
• Subjects who had previously received apremilast

• Subjects with severely impaired liver function (Child-Pugh Class C) or end-stage renal disease on dialysis or at least 1 of the following:

  • Serum creatinine > 1.5 mg/dL
  • Alanine aminotransferase or aspartate aminotransferase ≥ 1.5 × upper limit of normal
• Anyone affiliated with the site or sponsor and/or anyone who may consent under duress
• Any other sound medical reason as determined by the Investigator including any condition which may lead to an unfavorable risk-benefit of study participation, may interfere with study compliance or may confound results.

Contacts and Locations

Locations

United States, Missouri

Washington University Division of Dermatology

Saint Louis, Missouri, United States, 63108

Sponsors and Collaborators

Washington University School of Medicine

Celgene Corporation

Investigators

• Principal Investigator: Brian S. Kim, MD; Washington University School of Medicine

More Information

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03239106
• Other Study ID Numbers: CIP-ApremilastCC-10004
• First Posted: August 3, 2017
• Last Update Posted: September 4, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Washington University School of Medicine:

itch; pruritus; CIP

Additional relevant MeSH terms:

Pruritus; Skin Diseases; Skin Manifestations; Signs and Symptoms; Thalidomide; Apremilast; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Leprostatic Agents; Anti-Bacterial Agents; Anti-Infective Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents