Trial Outcomes & Findings for Neurokinin-1 Receptor Antagonist for the Treatment of Itch in EB Patients (NCT NCT02654483)

Last Updated: 2020-03-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

14 participants

Primary outcome timeframe

Baseline and 8 weeks

Results posted on

2020-03-23

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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.	Placebo Placebo tablets to be taken daily by mouth for 56 days Placebo: Matching tablets to VPD-737 tablets without active drug
Double-blind STARTED	7	7
Double-blind COMPLETED	7	7
Double-blind NOT COMPLETED	0	0
Open-label STARTED	5	3
Open-label COMPLETED	5	3
Open-label NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neurokinin-1 Receptor Antagonist for the Treatment of Itch in EB Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5 mg VPD-737 n=7 Participants 5 mg tablets of VPD-737 to be taken daily by mouth for 56 days VPD-737: VPD-737 inhibits the receptor neurokinin-1.	Placebo n=7 Participants Placebo tablets to be taken daily by mouth for 56 days Placebo: Matching tablets to VPD-737 tablets without active drug	Total n=14 Participants Total of all reporting groups
Age, Continuous	27.6 years STANDARD_DEVIATION 12.1 • n=5 Participants	22.9 years STANDARD_DEVIATION 8.0 • n=7 Participants	25.2 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
NRS daily itch severity score	6.1 score on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	6.6 score on a scale STANDARD_DEVIATION 1.0 • n=7 Participants	6.6 score on a scale STANDARD_DEVIATION 1.2 • n=5 Participants
NRS itch severity during bathing/dressing change	6.1 score on a scale STANDARD_DEVIATION 1.9 • n=5 Participants	6.2 score on a scale STANDARD_DEVIATION 2.2 • n=7 Participants	6.1 score on a scale STANDARD_DEVIATION 1.9 • n=5 Participants
EB wound size	42.6 mm^2 STANDARD_DEVIATION 65.8 • n=5 Participants	25.0 mm^2 STANDARD_DEVIATION 21.9 • n=7 Participants	34.2 mm^2 STANDARD_DEVIATION 48.3 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	5 mg VPD-737 n=7 Participants 7 subjects were treated with active drug	Placebo n=7 Participants 7 subjects were treated with placebo
Comparative Weekly Change in NRS Itch Score Over the 8-week Active Treatment Period	-2 score/week comparative change Interval -5.0 to 0.0	-1 score/week comparative change Interval -7.0 to 1.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	5 mg VPD-737 n=7 Participants 7 subjects were treated with active drug	Placebo n=7 Participants 7 subjects were treated with placebo
Wound Healing Determination	154.54 percentage change Standard Deviation 227	38.39 percentage change Standard Deviation 180

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	5 mg VPD-737 n=7 Participants 7 subjects were treated with active drug	Placebo n=7 Participants 7 subjects were treated with placebo
Change in Mean NRS Itch Score During Bathing/Dressing Changes	-2.5 score on a scale Interval -4.0 to 1.0	-2 score on a scale Interval -5.0 to 0.0

Adverse Events

Double-blind, 5 mg VPD-737

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Double-blind, Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 1 deaths

Open-label, 5 mg VPD-737 - 5 mg VPD-737

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Open-label, Placebo - 5 mg VPD-737

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind, 5 mg VPD-737 n=7 participants at risk 5 mg tablets of VPD-737 to be taken daily by mouth for 56 days VPD-737: VPD-737 inhibits the receptor neurokinin-1.	Double-blind, Placebo n=7 participants at risk Placebo tablets to be taken daily by mouth for 56 days Placebo: Matching tablets to VPD-737 tablets without active drug	Open-label, 5 mg VPD-737 - 5 mg VPD-737 n=5 participants at risk 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.	Open-label, Placebo - 5 mg VPD-737 n=3 participants at risk 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.
Respiratory, thoracic and mediastinal disorders pulmonary embolism	14.3% 1/7 • 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.	0.00% 0/7 • 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.	0.00% 0/5 • 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.	0.00% 0/3 • 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.
Cardiac disorders heart failure	14.3% 1/7 • 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.	0.00% 0/7 • 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.	0.00% 0/5 • 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.	0.00% 0/3 • 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.
Respiratory, thoracic and mediastinal disorders pleural effusion	14.3% 1/7 • 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.	0.00% 0/7 • 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.	0.00% 0/5 • 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.	0.00% 0/3 • 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.
Renal and urinary disorders nephropathy	0.00% 0/7 • 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.	14.3% 1/7 • 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.	0.00% 0/5 • 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.	0.00% 0/3 • 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.
Renal and urinary disorders hematuria	0.00% 0/7 • 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.	14.3% 1/7 • 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.	0.00% 0/5 • 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.	0.00% 0/3 • 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.

Other adverse events

Additional Information

Irene Bailey, CRC

Stanford University

Phone: 650-721-7149

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place