A Study Examining the Medication Apremilast as Treatment for Chronic Itch

Sponsor
Washington University School of Medicine (Other)
Overall Status
Completed
CT.gov ID
NCT03239106
Collaborator
Celgene Corporation (Industry)
10
1
1
21.6
0.5

Study Details

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
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
Actual Enrollment :
10 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
open labelopen label
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Study of Apremilast in Chronic Idiopathic Pruritus
Actual Study Start Date :
Dec 1, 2017
Actual Primary Completion Date :
Oct 31, 2018
Actual Study Completion Date :
Sep 19, 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 Names:
  • Otezla
  • Outcome Measures

    Primary Outcome Measures

    1. Absolute NRS Itch Score at Week 16 (End of Treatment) [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. 0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.

    Secondary Outcome Measures

    1. Absolute DLQI at Week 16 [Week 16]

      Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16 The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score).

    2. NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18 [Screening through Week 18 (follow up visit)]

      Participants' itch will be measured utilizing the 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. 0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.

    3. DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18 [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Site City State Country Postal Code
    1 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

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT03239106
    Other Study ID Numbers:
    • CIP-ApremilastCC-10004
    First Posted:
    Aug 3, 2017
    Last Update Posted:
    Jul 13, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Open Label
    Arm/Group Description All participants will received apremilast 30 mg PO BID.
    Period Title: Overall Study
    STARTED 10
    COMPLETED 3
    NOT COMPLETED 7

    Baseline Characteristics

    Arm/Group Title Open Label
    Arm/Group Description All participants will receive apremilast 30 mg PO BID.
    Overall Participants 10
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    70.5
    (11.7)
    Sex: Female, Male (Count of Participants)
    Female
    6
    60%
    Male
    4
    40%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    10%
    White
    9
    90%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    10
    100%
    24 hour numerical rating scale (NRS) itch score (units on a scale) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [units on a scale]
    9.25
    1 week NRS itch score (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    8
    (0.91)
    Dermatology Life Quality Index (units on a scale) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [units on a scale]
    11.5

    Outcome Measures

    1. Primary Outcome
    Title Absolute NRS Itch Score at Week 16 (End of Treatment)
    Description 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. 0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    All patients met criteria for chronic pruritus of unknown origin.
    Arm/Group Title Open Label
    Arm/Group Description All participants will receive apremilast 30 mg PO BID. The data were analyzed in an intent-to-treat manner with key primary and secondary endpoints measured as an absolute reduction in NRS itch and DLQI scores, respectively at week 16 from baseline. Thirty percent of the patients completed the study, which did not allow for meaningful intent-to-treat statistical analysis. As an alternative approach, we undertook a LOCF analysis by carrying forward to week 16.
    Measure Participants 10
    24 Hour NRS Itch Score
    7
    1 Week NRS Itch Score
    7.5
    2. Secondary Outcome
    Title Absolute DLQI at Week 16
    Description Participants will complete a 10 question Dermatology Quality of Life survey at baseline through Week 16 The DLQI is a numerical scale that scores multiple parameters of skin symptoms on a scale from 0 to 30. 0-1 = no effect at all on a patient's life (most favorable clinical outcome and minimum score), 1-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20 = very large effect on patient's life, 21-30 = extremely large effect on patient's life (worse clinical outcome and maximum score).
    Time Frame Week 16

    Outcome Measure Data

    Analysis Population Description
    Patients who met inclusion criteria with a diagnosis of chronic pruritus of unknown origin
    Arm/Group Title Open Label
    Arm/Group Description All participants will receive apremilast 30 mg PO BID. The data were analyzed in an intent-to-treat manner with key primary and secondary endpoints measured as an absolute reduction in NRS itch and DLQI scores, respectively at week 16 from baseline. Thirty percent of the patients completed the study, which did not allow for meaningful intent-to-treat statistical analysis. As an alternative approach, we undertook a LOCF analysis by carrying forward to week 16.
    Measure Participants 10
    Median (Inter-Quartile Range) [Score on a scale]
    13
    3. Secondary Outcome
    Title NRS at Screening, Baseline and Weeks 2,4,8,12,16,and 18
    Description Participants' itch will be measured utilizing the 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. 0 is the best score (minimum) and 10 is the worst score (maximum) in terms of clinical outcome. This is an ordinal scale that runs from 0 to 10.
    Time Frame Screening through Week 18 (follow up visit)

    Outcome Measure Data

    Analysis Population Description
    Although we started with 10 patients, patients dropped out of the study as it progressed.
    Arm/Group Title Open Label
    Arm/Group Description All participants will receive Apremilast 30 mg BID. Apremilast: Apremilast 30 mg BID daily
    Measure Participants 10
    Screening
    8.9
    (1.1)
    Baseline (Week 0)
    7.9
    (1.6)
    Week 2
    5.7
    (3.7)
    Week 4
    6.5
    (4.1)
    Week 8
    7.0
    (4.2)
    Week 12
    5.7
    (5.1)
    Week 16
    3.0
    (5.2)
    Week 18
    1.0
    (0.0)
    4. Secondary Outcome
    Title DLQI at Screening, Baseline, and Weeks 2,4,8,12,16 and 18
    Description Participants will complete a 10 question Dermatology Life Quality Index questionnaire at Screening, Baseline, and Weeks 2,4,8,12,16,18.
    Time Frame Screening through Week 18 (follow up visit)

    Outcome Measure Data

    Analysis Population Description
    Although we started with 10 patients, patients dropped out of the study as it progressed.
    Arm/Group Title Open Label
    Arm/Group Description All participants will receive apremilast 30 mg PO BID. The data were analyzed in an intent-to-treat manner with key primary and secondary endpoints measured as an absolute reduction in NRS itch and DLQI scores, respectively at week 16 from baseline. Thirty percent of the patients completed the study, which did not allow for meaningful intent-to-treat statistical analysis. As an alternative approach, we undertook a LOCF analysis by carrying forward to week 16.
    Measure Participants 10
    Screening
    15.3
    (7.3)
    Baseline (Week 0)
    13.7
    (7.6)
    Week 2
    13.3
    (9.9)
    Week 4
    10.8
    (9.9)
    Week 8
    7.5
    (6.5)
    Week 12
    4.7
    (6.4)
    Week 16
    2.3
    (2.1)
    Week 18
    5.0
    (5.7)

    Adverse Events

    Time Frame Adverse event data were collected until the end of the study visit at Week 18 or earlier if the subject dropped out of the study.
    Adverse Event Reporting Description
    Arm/Group Title Open Label
    Arm/Group Description All participants will receive apremilast 30 mg PO BID.
    All Cause Mortality
    Open Label
    Affected / at Risk (%) # Events
    Total 0/10 (0%)
    Serious Adverse Events
    Open Label
    Affected / at Risk (%) # Events
    Total 0/10 (0%)
    Other (Not Including Serious) Adverse Events
    Open Label
    Affected / at Risk (%) # Events
    Total 5/10 (50%)
    Gastrointestinal disorders
    Nausea 3/10 (30%) 3
    Diarrhea 3/10 (30%) 3
    Vomiting 1/10 (10%) 1
    General disorders
    Decreased appetite 1/10 (10%) 1
    Nervous system disorders
    Fatigue 1/10 (10%) 1
    Headache 1/10 (10%) 1
    Presyncope 1/10 (10%) 1

    Limitations/Caveats

    Due to the high dropout rate in this study a meaningful intent-to-treat analysis was not possible. Therefore, in addition, we attempted a last observation carried forward (LOCF) analysis as well.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Brian Kim, Associate Professor of Medicine
    Organization Washington University School of Medicine
    Phone 314-273-1376
    Email briankim@wustl.edu
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT03239106
    Other Study ID Numbers:
    • CIP-ApremilastCC-10004
    First Posted:
    Aug 3, 2017
    Last Update Posted:
    Jul 13, 2021
    Last Verified:
    Jun 1, 2021