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| Name | Class |
|---|---|
| Epidermolysis Bullosa Research Partnership | OTHER_GOV |
| Vyne Therapeutics Inc. | INDUSTRY |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5 mg VPD-737 | Experimental | 5 mg tablets of VPD-737 to be taken daily by mouth for 56 days |
|
| Placebo | Placebo Comparator | Placebo tablets to be taken daily by mouth for 56 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VPD-737 | Drug | VPD-737 inhibits the receptor neurokinin-1. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 8 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 8 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean Tang, MD, PhD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford | Stanford | California | 94305 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31541747 | Result | Chiou AS, Choi S, Barriga M, Dutt-Singkh Y, Solis DC, Nazaroff J, Bailey-Healy I, Li S, Shu K, Joing M, Kwon P, Tang JY. Phase 2 trial of a neurokinin-1 receptor antagonist for the treatment of chronic itch in patients with epidermolysis bullosa: A randomized clinical trial. J Am Acad Dermatol. 2020 Jun;82(6):1415-1421. doi: 10.1016/j.jaad.2019.09.014. Epub 2019 Sep 18. |
| Label | URL |
|---|---|
| Phase 2 trial of a neurokinin-1 receptor antagonist for the treatment of chronic itch in patients with epidermolysis bullosa: A randomized clinical trial. | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Placebo | Placebo tablets to be taken daily by mouth for 56 days Placebo: Matching tablets to VPD-737 tablets without active drug |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Double-blind |
| |||||||||||||
| Open-label |
|
All study participants
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Placebo | Placebo tablets to be taken daily by mouth for 56 days Placebo: Matching tablets to VPD-737 tablets without active drug |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | score/week comparative change | Baseline and 8 weeks |
Up to 10 months; some patients did not proceed to the open-label arm immediately and were monitored for AEs during the period between arms.
AE grading by severity based on judgement of investigators. Grade I = mild, Grade II = moderate, Grade III = severe. AEs were captured/followed at all study visits.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Double-blind, 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| nausea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Irene Bailey, CRC | Stanford University | 650-721-7149 | baileyhi@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Apr 17, 2019 | Apr 18, 2019 | ICF_000.pdf |
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 9, 2017 | Apr 18, 2019 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D004820 | Epidermolysis Bullosa |
| D011537 | Pruritus |
| ID | Term |
|---|---|
| D012868 | Skin Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012873 | Skin Diseases, Genetic |
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| ID | Term |
|---|---|
| C551592 | serlopitant |
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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
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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.
| Placebo | Other | Matching tablets to VPD-737 tablets without active drug |
|
| 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. |
| Baseline and 8 weeks |
| NOT COMPLETED |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| NRS daily itch severity score | Mean daily itch score as measured by patient self-reports using a numeric rating scale (NRS) for itch severity and the Stanford EB itch questionnaire. NRS is included in the Stanford EB Itch survey. The NRS is comprised of one item and represents the numbers 0 ("no itch") to 10 ("worst imaginable itch"). | Mean | Standard Deviation | score on a scale |
|
| NRS itch severity during bathing/dressing change | Mean itch score during bathing/dressing change as measured by patient self-reports using a numeric rating scale (NRS) for itch severity and the Stanford EB itch questionnaire. NRS is included in the Stanford EB Itch survey. The NRS is comprised of one item and represents the numbers 0 ("no itch") to 10 ("worst imaginable itch"). | Mean | Standard Deviation | score on a scale |
|
| EB wound size | Target wounds are identified and quantified at baseline using the Canfield image analysis system. | Mean | Standard Deviation | mm^2 |
|
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | percentage change | Baseline and 8 weeks |
|
|
|
| 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. | 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. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline and 8 weeks |
|
|
|
| 0 |
| 7 |
| 1 |
| 7 |
| 6 |
| 7 |
| EG001 | Double-blind, Placebo | Placebo tablets to be taken daily by mouth for 56 days Placebo: Matching tablets to VPD-737 tablets without active drug | 1 | 7 | 1 | 7 | 7 | 7 |
| EG002 | Open-label, 5 mg VPD-737 - 5 mg VPD-737 | 5 mg tablets of VPD-737 to be taken daily by mouth for 56 days, followed by a wash out period and, 5 mg tablets of VPD-737 to be taken daily by mouth for 2 months. | 0 | 5 | 0 | 5 | 2 | 5 |
| EG003 | Open-label, Placebo - 5 mg VPD-737 | Placebo tablets to be taken daily by mouth for 56 days, followed by a wash out period and, 5 mg tablets of VPD-737 to be taken daily by mouth for 2 months. | 0 | 3 | 0 | 3 | 3 | 3 |
| heart failure | Cardiac disorders | Systematic Assessment |
|
| pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| nephropathy | Renal and urinary disorders | Systematic Assessment |
|
| hematuria | Renal and urinary disorders | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| otitis | Ear and labyrinth disorders | Systematic Assessment |
|
| headache | Nervous system disorders | Systematic Assessment |
|
| somnolence | Nervous system disorders | Systematic Assessment |
|
| dizziness | Nervous system disorders | Systematic Assessment |
|
| infection (wound) | Infections and infestations | Systematic Assessment |
|
| exacerbation of pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| flu-like symptoms | General disorders | Systematic Assessment |
|
| cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| pain | Injury, poisoning and procedural complications | Systematic Assessment | unrelated to biopsy site |
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| toothache | Gastrointestinal disorders | Systematic Assessment |
|
| infection | Infections and infestations | Systematic Assessment | bronchial |
|
| fever | General disorders | Systematic Assessment |
|
| skin ulceration | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| upper respiratory infection | Infections and infestations | Systematic Assessment |
|
| constipation | Gastrointestinal disorders | Systematic Assessment |
|
| dysesthesia | Nervous system disorders | Systematic Assessment | formication |
|
| pain | Musculoskeletal and connective tissue disorders | Systematic Assessment | facial/jaw pain |
|
| dyspepsia | Gastrointestinal disorders | Systematic Assessment |
|
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| D030342 | Genetic Diseases, Inborn |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D012872 | Skin Diseases, Vesiculobullous |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |