A Study Examining the Medication Apremilast as Treatment for Chronic Itch
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
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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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).
- 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.
- 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
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.- CIP-ApremilastCC-10004
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
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
|
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
|
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)
|
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
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 |
briankim@wustl.edu |
- CIP-ApremilastCC-10004