Epidermolysis Bullosa, Pruritus
Conditions
Brief summary
Our goal is to determine whether daily oral administration of VPD-737 (5 mg) is effective and safe in treating moderate to severe pruritus in patients with Epidermolysis Bullosa (EB).
Detailed description
Itch is the most common complaint reported by patients with EB of all subtypes, and there is no current effective treatment. Itch often triggers scratching that creates new wounds and increases EB disease severity. This study aims to target the physiological mechanisms of pruritus (itch) in patients with EB. Substance P is a major mediator of pruritus and binds to the receptor neurokinin-1 (NK1), which is expressed in the central nervous system and the skin. VPD-737 (serlopitant), a novel drug that inhibits the NK1 receptor, has been shown to reduce severe itch in a previous study of 257 adult patients with chronic pruritus. Each patient will be un-blinded individually after completing 3 months of study period. All patients who complete the study will be offered a 2-month period on active drug. Patient who received active drug in the first period will be contacted and asked if they would like to continue on active drug for an additional 2 months. Patients who received placebo in the first period will be contacted and asked if they would like to repeat the study on open label for 2 months.
Interventions
DRUGVPD-737
VPD-737 inhibits the receptor neurokinin-1.
OTHERPlacebo
Matching tablets to VPD-737 tablets without active drug
Sponsors
Epidermolysis Bullosa Research Partnership
Vyne Therapeutics Inc.
Jean Yuh Tang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Research personnel not involved in this study was responsible for blinding. This was the only personnel with access to the code linking study drug bottle numbers to treatment (i.e. active or placebo). The code was broken when all data was captured and locked on an electronic data capture system.
Intervention model description
Phase 2 investigator-initiated, randomized, double-blind, placebo-controlled, parallel-arm trial evaluating the comparative effect of serlopitant 5 mg by mouth daily versus placebo in treatment of chronic pruritus in pediatric and adult EB patients
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of Epidermolysis Bullosa (EB) and pruritus
Exclusion criteria
* Chronic liver or renal disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period | Baseline and 8 weeks | Determine the efficacy of Serlopitant compared with placebo on reducing EB-associated daily itch score as measured by patient self-reports using a numeric rating scale (NRS) for itch severity.The NRS is comprised of one item and represents the numbers 0 (no itch) to 10 (worst imaginable itch). Because itch is subjective and can vary day to day, nightly NRS scores were recorded in patients' Itch Diaries. NRS recorded by subject daily, from screening visit through the end of the study. This study was designed to detect differences between the two treatment groups. The primary endpoint was the comparative weekly change in Numeric Rating Scale (NRS) itch severity score from baseline over 8 weeks; derived from a linear mixed effects model which utilizes observations from both the treatment and placebo groups to generate an interaction term of interest. Itch severity changes from day to day and this model can more appropriately report trends in patients' itch severity with treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wound Healing Determination | Baseline and 8 weeks | Wound dimensions, including length, width, and area (in cm2), will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Overall mean % change from baseline is reported as the secondary endpoint. |
| Change in Mean NRS Itch Score During Bathing/Dressing Changes | Baseline and 8 weeks | Itch is exacerbated by activities such as dressing changes or bathing. NRS itch score during bathing or dressing in the past 24 hours were collected. Numeric rating scale (NRS) for itch severity is comprised of one item and represents the numbers 0 (no itch) to 10 (worst imaginable itch). This study was designed to detect differences between the two treatment groups. This secondary endpoint was the comparative change in Numeric Rating Scale (NRS) itch severity score during bathing/dressing changes from baseline over 8 weeks as determined by application of a linear mixed effects model. |
Countries
United States
Participant flow
Pre-assignment details
A 30-day washout period from prohibited medications (if applicable) is included prior to arm assignment. All patients who complete the double-blinded period will be offered a 2-month period on active drug.
Participants by arm
| Arm | Count |
|---|---|
| 5 mg VPD-737 5 mg tablets of VPD-737 to be taken daily by mouth for 56 days
VPD-737: VPD-737 inhibits the receptor neurokinin-1. | 7 |
| Placebo Placebo tablets to be taken daily by mouth for 56 days
Placebo: Matching tablets to VPD-737 tablets without active drug | 7 |
| Total | 14 |
Baseline characteristics
| Characteristic | 5 mg VPD-737 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 27.6 years STANDARD_DEVIATION 12.1 | 25.2 years STANDARD_DEVIATION 10.2 | 22.9 years STANDARD_DEVIATION 8 |
| EB wound size | 42.6 mm^2 STANDARD_DEVIATION 65.8 | 34.2 mm^2 STANDARD_DEVIATION 48.3 | 25.0 mm^2 STANDARD_DEVIATION 21.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 10 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| NRS daily itch severity score | 6.1 score on a scale STANDARD_DEVIATION 1.9 | 6.6 score on a scale STANDARD_DEVIATION 1.2 | 6.6 score on a scale STANDARD_DEVIATION 1 |
| NRS itch severity during bathing/dressing change | 6.1 score on a scale STANDARD_DEVIATION 1.9 | 6.1 score on a scale STANDARD_DEVIATION 1.9 | 6.2 score on a scale STANDARD_DEVIATION 2.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 3 Participants |
| Region of Enrollment United States | 7 participants | 14 participants | 7 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 7 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 1 / 7 | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 6 / 7 | 7 / 7 | 2 / 5 | 3 / 3 |
| serious Total, serious adverse events | 1 / 7 | 1 / 7 | 0 / 5 | 0 / 3 |
Outcome results
Primary
Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period
Determine the efficacy of Serlopitant compared with placebo on reducing EB-associated daily itch score as measured by patient self-reports using a numeric rating scale (NRS) for itch severity.The NRS is comprised of one item and represents the numbers 0 (no itch) to 10 (worst imaginable itch). Because itch is subjective and can vary day to day, nightly NRS scores were recorded in patients' Itch Diaries. NRS recorded by subject daily, from screening visit through the end of the study. This study was designed to detect differences between the two treatment groups. The primary endpoint was the comparative weekly change in Numeric Rating Scale (NRS) itch severity score from baseline over 8 weeks; derived from a linear mixed effects model which utilizes observations from both the treatment and placebo groups to generate an interaction term of interest. Itch severity changes from day to day and this model can more appropriately report trends in patients' itch severity with treatment.
Time frame: Baseline and 8 weeks
Population: The relative effect of drug on the mean daily change in NRS itch severity score as compared to baseline is calculated and serves as the primary endpoint. Data is reported as point/week change (delta) in NRS itch score.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 5 mg VPD-737 | Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period | -2 score/week comparative change |
| Placebo | Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period | -1 score/week comparative change |
Secondary
Change in Mean NRS Itch Score During Bathing/Dressing Changes
Itch is exacerbated by activities such as dressing changes or bathing. NRS itch score during bathing or dressing in the past 24 hours were collected. Numeric rating scale (NRS) for itch severity is comprised of one item and represents the numbers 0 (no itch) to 10 (worst imaginable itch). This study was designed to detect differences between the two treatment groups. This secondary endpoint was the comparative change in Numeric Rating Scale (NRS) itch severity score during bathing/dressing changes from baseline over 8 weeks as determined by application of a linear mixed effects model.
Time frame: Baseline and 8 weeks
Population: The relative effect of drug on the mean change in NRS itch severity score during dressing changes as compared to baseline is calculated and serves as the secondary endpoint.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 5 mg VPD-737 | Change in Mean NRS Itch Score During Bathing/Dressing Changes | -2.5 score on a scale |
| Placebo | Change in Mean NRS Itch Score During Bathing/Dressing Changes | -2 score on a scale |
Secondary
Wound Healing Determination
Wound dimensions, including length, width, and area (in cm2), will be obtained using the Canfield system. Changes in dimensions between visits as well as changes in dimensions from baseline will be recorded. Overall mean % change from baseline is reported as the secondary endpoint.
Time frame: Baseline and 8 weeks
Population: Eligible participants were: age 13 and older with a clinical diagnosis of EB and a Numeric Rating Scale (NRS) score for pruritus of ≥4 at baseline on average itch or itch during bathing or dressing in the past 24 hours. Patients were required to have itch symptoms lasting ≥6 weeks that did not respond well to the current standard of care.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg VPD-737 | Wound Healing Determination | 154.54 percentage change | Standard Deviation 227 |
| Placebo | Wound Healing Determination | 38.39 percentage change | Standard Deviation 180 |