Pruritus
Conditions
Keywords
Dupilumab
Brief summary
To investigate the potential efficacy of dupilumab in the treatment of moderate to severe chronic hepatic pruritus.
Detailed description
This is a 22-week (2 week screening, 18-week treatment period followed by a 2 week followup), phase II, open label, exploratory study to investigate the potential efficacy of FDA approved dupilumab in the treatment of adults with moderate to severe chronic hepatic pruritus. Subjects will be screened at outpatient clinic visit appointments and interested qualified subjects will be consented and offered participation in this trial. Once consent has been obtained, baseline values will be established and subjects will begin treatment and follow-up for the next 20 weeks. A final visit will be needed for evaluation and questionnaire completion.
Interventions
Subcutaneous (SC) dupilumab selected for this study is 300 mg every 2 weeks for 18 weeks.
Sponsors
Regeneron Pharmaceuticals
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and/or female subjects 18 years or older with chronic pruritus of moderate to severe severity in the setting of intrahepatic or extrahepatic cholestatic liver disease. Chronic is defined as greater than 6 weeks of symptom duration. Pruritus severity is based on the peak pruritus numerical rating score of ≥ 4 (moderate severity). * Documentation of a personally signed and dated informed consent indicating that the subject or their legally acceptable representative has been informed of all pertinent aspects of the trial. * Willingness and ability to comply with scheduled clinic visits, physical exams, laboratory tests, questionnaires, effective contraception use, and other trial procedures.
Exclusion criteria
* Male and/or female subjects under 18 years of age. * Pruritus due to a primary inflammatory skin dermatosis or other forms of psychogenic pruritus utilizing skin biopsies as needed. * Pregnant females * History of intrahepatic cholestasis of pregnancy * Any form of chronic hepatic pruritus associated with underlying malignancy * Liver transplant recipients * Allergy to dupilumab or its ingredients * Inability to provide informed consent * Concomitant use of selective opioid antagonists * Subjects with severe asthma (requiring high-dose inhaled or systemic corticosteroids) will be excluded from the study. * Patients with known helminth infections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Peak Pruritus Numerical Rating Score (PRNS) | Baseline; 20 weeks | Pruritus severity is measured using the peak PNRS assessed as a single, self-completed item that assesses the intensity of peak (worst) pruritus during the past 24 hours using the query: On a scale of 0 to 10, with 0 being 'no itch 'and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Measured before and after treatment. Scores range from 0 to 10 with higher scores indicating a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Weekly Average Peak Pruritus Numerical Rating Score (PRNS) ≥3 From Baseline | Baseline; week 6,12,18 | Pruritus severity is measured using the peak PNRS assessed as a single, self-completed item that assesses the intensity of peak (worst) pruritus during the past 24 hours using the query: On a scale of 0 to 10, with 0 being 'no itch 'and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Scores range from 0 to 10 with higher scores indicating a worse outcome. |
| Verbal Rating Scale (VRS) Score | Baseline; week 12,18 | The number of subjects who rated their intensity of pruritus as 0=none, 1=mild, 2-moderate, 3=severe. The verbal rating scale measures the intensity of pruritus. Subjects are asked to rate their pruritus intensity as 0=none; 1= mild; 2=moderate; and 3=severe/intense. Scores range from 0 to 3, with higher scores indicating a worse outcome. |
| Change in Chronic Liver Disease Questionnaire (CLDQ) Score | Baseline; 18 Weeks | This is a validated 29 question quality life instrument for patients with chronic liver disease evaluating systemic symptoms, fatigue, physical activity, emotional function, and worry. Subjects are asked to respond to each question using the following scale: 6=all of the time; 5=most of the time; 4=a good bit of the time; 3=some of the time; 2=a little of the time; 1=hardly any of the time; and 0=none of the time. Total scores range from 0 to 174 with lower scores indicating better health-related quality of life. |
| Change in 5D Pruritus Score | Baseline; 18 Weeks | This is a multidimensional questionnaire designed to assess the degree, duration, direction, disability and distribution of pruritus longitudinally with scoring ranging from 5=no pruritus/well-controlled to 25=severe pruritus/poorly controlled, with higher scores indicating a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dupilumab Subcutaneous (SC) dupilumab selected for this study was 300 mg every 2 weeks for 18 weeks.
Dupilumab 300Mg Solution for Injection: Subcutaneous (SC) dupilumab selected for this study was 300 mg every 2 weeks for 18 weeks. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Dupilumab |
|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 14.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Change in Peak Pruritus Numerical Rating Score (PRNS)
Pruritus severity is measured using the peak PNRS assessed as a single, self-completed item that assesses the intensity of peak (worst) pruritus during the past 24 hours using the query: On a scale of 0 to 10, with 0 being 'no itch 'and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Measured before and after treatment. Scores range from 0 to 10 with higher scores indicating a worse outcome.
Time frame: Baseline; 20 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab | Change in Peak Pruritus Numerical Rating Score (PRNS) | -3.1 score on a scale | Standard Deviation 3.9 |
Secondary
Change in 5D Pruritus Score
This is a multidimensional questionnaire designed to assess the degree, duration, direction, disability and distribution of pruritus longitudinally with scoring ranging from 5=no pruritus/well-controlled to 25=severe pruritus/poorly controlled, with higher scores indicating a worse outcome.
Time frame: Baseline; 18 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab | Change in 5D Pruritus Score | -7.3 score on a scale | Standard Deviation 4.6 |
p-value: 0.006t-test, 2 sided
Secondary
Change in Chronic Liver Disease Questionnaire (CLDQ) Score
This is a validated 29 question quality life instrument for patients with chronic liver disease evaluating systemic symptoms, fatigue, physical activity, emotional function, and worry. Subjects are asked to respond to each question using the following scale: 6=all of the time; 5=most of the time; 4=a good bit of the time; 3=some of the time; 2=a little of the time; 1=hardly any of the time; and 0=none of the time. Total scores range from 0 to 174 with lower scores indicating better health-related quality of life.
Time frame: Baseline; 18 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dupilumab | Change in Chronic Liver Disease Questionnaire (CLDQ) Score | 25.7 score on a scale | Standard Deviation 38.7 |
p-value: 0.13t-test, 2 sided
Secondary
Change in Weekly Average Peak Pruritus Numerical Rating Score (PRNS) ≥3 From Baseline
Pruritus severity is measured using the peak PNRS assessed as a single, self-completed item that assesses the intensity of peak (worst) pruritus during the past 24 hours using the query: On a scale of 0 to 10, with 0 being 'no itch 'and 10 being 'worst itch imaginable', how would you rate your itch at the worst moment during the previous 24 hours?. Scores range from 0 to 10 with higher scores indicating a worse outcome.
Time frame: Baseline; week 6,12,18
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dupilumab | Change in Weekly Average Peak Pruritus Numerical Rating Score (PRNS) ≥3 From Baseline | Week 6 | -3.2 score on a scale | Standard Deviation 3.6 |
| Dupilumab | Change in Weekly Average Peak Pruritus Numerical Rating Score (PRNS) ≥3 From Baseline | Week 12 | -3.5 score on a scale | Standard Deviation 3.9 |
| Dupilumab | Change in Weekly Average Peak Pruritus Numerical Rating Score (PRNS) ≥3 From Baseline | Week 18 | -4.1 score on a scale | Standard Deviation 4.4 |
Secondary
Verbal Rating Scale (VRS) Score
The number of subjects who rated their intensity of pruritus as 0=none, 1=mild, 2-moderate, 3=severe. The verbal rating scale measures the intensity of pruritus. Subjects are asked to rate their pruritus intensity as 0=none; 1= mild; 2=moderate; and 3=severe/intense. Scores range from 0 to 3, with higher scores indicating a worse outcome.
Time frame: Baseline; week 12,18
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dupilumab | Verbal Rating Scale (VRS) Score | Baseline-Mild | 0 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Baseline-None | 0 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Baseline-Moderate | 4 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Baseline-Severe | 5 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 18-Moderate | 2 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 18-Severe | 0 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 12-None | 1 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 12-Mild | 4 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 12-Moderate | 3 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 12-Severe | 0 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 18-None | 2 Participants |
| Dupilumab | Verbal Rating Scale (VRS) Score | Week 18-Mild | 4 Participants |
Comparison: Week 12p-value: 0.018Wilcoxon (Mann-Whitney)
Comparison: Week 18p-value: 0.021Wilcoxon (Mann-Whitney)