Cholinergic Urticaria
Conditions
Brief summary
Phase 2a trial to assess the efficacy and safety of LEO 152020 in adult patients with cholinergic urticaria
Detailed description
This is a phase 2a, randomised, double-blind, placebo-controlled, cross-over trial conducted in Germany at 3-6 sites. Subjects will be randomised to one of two treatment sequences (A and B). Each treatment period will last 7 days with a wash-out period of 7 days between treatments. Half of the subjects will start with treatment A followed by treatment B while the other half will start with treatment B followed by treatment A. A safety follow-up visit will be performed 3 days after last dose of the tested medication. The main assessment is an urticaria activity score. After a Pulse-controlled ergometry (PCE) provocation test subjects will be rated on their number of wheals and their itch severity, resulting in a sum score ranging from 0 to 6 points.
Interventions
DRUGLEO 152020
LEO 152020 is a small drug molecule which can block the histamine 4 receptor (H4R). LEO 152020 is a tablet for oral administration.
DRUGLEO 152020 placebo
LEO 152020 placebo is a tablet for oral administration. LEO 152020 placebo contains the same excipients in the same concentration as the LEO 152020 tablet, except the medical ingredient, LEO 152020.
Sponsors
LEO Pharma
JW Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Placebo-controlled
Intervention model description
Each treatment period will last 7 days with a wash-out period of 7 days between treatments
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Subject with a history of Cholinergic urticaria diagnosis for ≥ 6 months * Subject has active and uncontrolled Cholinergic urticaria disease at the time of screening and randomisation, as defined by the following: 1. Urticaria control test \< 12 at screening 2. Urticaria Activity Score post-provocation ≥ 3 * Recent history (within 6 months of screening) with documented inadequate response to standard dose as to marketing authorization of H1 antihistamines. Main
Exclusion criteria
* Other clearly dominating forms\* of urticaria as aetiology for wheal and flare type reactions \*These diseases are allowed as comorbidities, if cholinergic urticaria is the dominating form of chronic urticaria, * Systemic immunosuppressive medications within 4 weeks prior to screening, * Systemic drugs (e.g. oral drug) with antihistamine properties including H1 antihistamines and some antidepressants (e.g. tricyclic antidepressants) and H2 antihistamines 1 week prior to randomisation and throughout the trial. However, topical antihistamines in the form of nasal spray and eyedrops are allowed in the standard prescribed dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Post-provocation Urticaria Activity Score (UASprovo) | Baseline to Day 7 | The Urticaria Activity Score (UAS) rates a participants' number of wheals and their itch severity on a scale from 0 to 6, with 6 being the most severe. UAS is assessed after provocation of urticaria by moderate exercise to cause sweating. |
Secondary
| Measure | Time frame |
|---|---|
| Number of Treatment Emergent Adverse Events | From start of each treatment period (day 1 for the 1st treatment period or day 15 or 22 for the 2nd treatment period) until 3 days after end of each treatment period (day 11 for the 1st treatment period or day 25 or 32 for the 2nd treatment period) |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active - Placebo Patients will receive active treatment for 7 days, followed by a washout period of 7 days and then placebo for 7 days
LEO 152020: LEO 152020 is a small drug molecule which can bind to the histamine 4 receptor (H4R). LEO 152020 is a tablet for oral administration.
LEO 152020 placebo: LEO 152020 placebo is a tablet for oral administration. LEO 152020 placebo contains the same excipients in the same concentration as the LEO 152020 tablet, except the medical ingredient, LEO 152020. | 11 |
| Placebo - Active Patients will receive placebo for 7 days, followed by a washout period of 7 days and then active treatment for 7 days
LEO 152020: LEO 152020 is a small drug molecule which can bind to the histamine 4 receptor (H4R). LEO 152020 is a tablet for oral administration.
LEO 152020 placebo: LEO 152020 placebo is a tablet for oral administration. LEO 152020 placebo contains the same excipients in the same concentration as the LEO 152020 tablet, except the medical ingredient, LEO 152020. | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period A | Adverse Event | 0 | 1 |
| Wash Out | Met exclusion criteria for next treatment phase | 1 | 0 |
Baseline characteristics
| Characteristic | Active - Placebo | Total | Placebo - Active |
|---|---|---|---|
| Age, Continuous | 25 years | 25 years | 25 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 19 Participants | 8 Participants |
| Region of Enrollment Germany | 11 participants | 20 participants | 9 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 9 / 19 | 6 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Change From Baseline in Post-provocation Urticaria Activity Score (UASprovo)
The Urticaria Activity Score (UAS) rates a participants' number of wheals and their itch severity on a scale from 0 to 6, with 6 being the most severe. UAS is assessed after provocation of urticaria by moderate exercise to cause sweating.
Time frame: Baseline to Day 7
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active | Change From Baseline in Post-provocation Urticaria Activity Score (UASprovo) | -1.1 scores on a scale | Standard Deviation 2.1 |
| Placebo | Change From Baseline in Post-provocation Urticaria Activity Score (UASprovo) | -0.5 scores on a scale | Standard Deviation 1.7 |
Comparison: The primary endpoint, change from baseline in post-provocation Urticaria Activity Score (UASprovo) to the end of the treatment period, was compared between treatments with the null hypothesis that they are equal against the alternative that they are different. The primary efficacy endpoint was analysed using a linear mixed model, containing treatment, period and carryover effects, the factor site and additionally the value of UASprovo at baseline as a covariate.p-value: 0.27795% CI: [-1.69, 0.53]Mixed Models Analysis
Secondary
Number of Treatment Emergent Adverse Events
Time frame: From start of each treatment period (day 1 for the 1st treatment period or day 15 or 22 for the 2nd treatment period) until 3 days after end of each treatment period (day 11 for the 1st treatment period or day 25 or 32 for the 2nd treatment period)
Population: Safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active | Number of Treatment Emergent Adverse Events | 9 Number of AEs |
| Placebo | Number of Treatment Emergent Adverse Events | 5 Number of AEs |