Chronic Urticaria
Conditions
Keywords
urticaria
Brief summary
Randomised, double-blind, placebo-controlled study evaluating the effects of miltefosine on skin lesions in patients with treatment resistant chronic urticaria. Treatment resistance is defined by insufficient treatment response after a minimum of 1 week therapy with the maximum labelled dose of a non-sedating antihistamine. Eligible subjects will be enrolled at baseline 8 (+/- 1) days after screening. 75 Patients will be randomised in a 2:1 ratio to one of the following treatment groups as add-on to the ongoing therapy with a non-sedating antihistamine for treatment period of 4 weeks: 25 placebo and 50 active drug Efficacy and safety evaluations are done at baseline day 7, 14, 21 safety, only) and 28 (or end of treatment) and at day 56 (28 days after end of treatment).
Interventions
DRUGMiltefosine
50 or 100 or 150mg per day
DRUGPlacebo
Placebo
Sponsors
Charite University, Berlin, Germany
Marcus Maurer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Informed consent signed and dated Outpatients with moderate to severe spontaneous CU defined by UAS of ≥15 (under the maximum labelled dose of a non-sedating antihistamine Resistant to standard treatment with antihistamines after a minimum of 7 days therapy with the maximum labelled dose of a non-sedating antihistamine (levocetirizine, cetirizine, fexofenadine, desloratadine, loratadine, ebastine, mizolastine Aged more than 18 years Reliable method of contraception for both women of childbearing potential as well as men during the study and 3 months thereafter. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner.
Exclusion criteria
Pregnancy or lactation Participation in another clinical trial within the last 30 days Body weight ≤ 45 kg Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1 number 4 AMG (Arzneimittelgesetz). Skin symptoms caused primarily by physical urticaria Urticaria vasculitis Known hypersensitivity to miltefosine Retinal pathology Leishmaniasis Gastrointestinal disturbances which may influence oral resorption (e.g. chronic diarrhoea diseases, congenital malformations or major surgical resection of gastrointestinal tract). History within 5 years or presence of myocardial infarction or any other major cardiac disorder. Serum-creatinine and/or BUN 1.5 times above the upper reference value GOT and/or GPT and/or alkaline phosphatase 3 times above the upper reference value). Sjögren-Larsson-Syndrome. Malignancy within the last 5 years requiring chemotherapy or radiation therapy. Mental disorders that interfere with the evaluation of study end-points Drug or alcohol dependency Any other chronic or acute illness requiring systemic treatment which might have any influence on the outcome of the study in the 4 weeks before start of treatment and during the study (investigator's decision). Immunodeficiency including HIV During the past 10 days before start of treatment and during the study Topical steroids H2 antihistamines Leukotriene antagonists H1 antihistamine other then basic therapy During the past 2 weeks before start of treatment and during the study Ketotifen Doxepin During the past 4 weeks before start of treatment and during the study Systemic corticosteroids UV therapy including PUVA Systemic immunosuppressives including corticosteroids, immunomodulators, immunostimulants During the past 12 weeks before start of treatment and during the study Astemizole Tranquilizers, antidepressants, sedatives, hypnotics, antiepileptics and other CNS active agents, except treatment with tricyclics that is stable for at least 12 weeks prior to screening and throughout the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urticaria Activity Score (% Change From Baseline) | Day 28 | The weekly UAS was calculated by adding the daily scores over one week. During the whole course of the study patients recorded the amount of wheals and the intensity of itching as well as the occurrence of swelling in ranges between 0 and 3. These daily scores were used to calculate urticaria activity scores (UAS) as follows: Daily UAS are calculated by adding the score points obtained for the symptom categories number of wheals and intensity of pruritus. Number of wheals is scored as 0 = no wheals, 1 = some wheals (\<20), 2 = moderate number of wheals (20-50), 3 = more than 50 wheals. Intensity of pruritus is scored as 0 = no itching; 1 = mild itching, not irritating; 2 = moderate itching, normal daily activity and sleep is possible; and 3 = severe itching, normal daily activity and sleep is impaired. The maximum score is 42. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Miltefosine | 50 |
| Placebo | 26 |
| Total | 76 |
Baseline characteristics
| Characteristic | Miltefosine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 4 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants | 22 Participants | 66 Participants |
| Age, Continuous | 45.0 years STANDARD_DEVIATION 12.4 | 42.6 years STANDARD_DEVIATION 12.5 | 44 years STANDARD_DEVIATION 24.9 |
| Gender Female | 28 Participants | 14 Participants | 42 Participants |
| Gender Male | 22 Participants | 12 Participants | 34 Participants |
| Region of Enrollment Germany | 50 participants | 26 participants | 76 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 44 / 50 | 17 / 26 |
| serious Total, serious adverse events | 0 / 50 | 0 / 26 |
Outcome results
Primary
Urticaria Activity Score (% Change From Baseline)
The weekly UAS was calculated by adding the daily scores over one week. During the whole course of the study patients recorded the amount of wheals and the intensity of itching as well as the occurrence of swelling in ranges between 0 and 3. These daily scores were used to calculate urticaria activity scores (UAS) as follows: Daily UAS are calculated by adding the score points obtained for the symptom categories number of wheals and intensity of pruritus. Number of wheals is scored as 0 = no wheals, 1 = some wheals (\<20), 2 = moderate number of wheals (20-50), 3 = more than 50 wheals. Intensity of pruritus is scored as 0 = no itching; 1 = mild itching, not irritating; 2 = moderate itching, normal daily activity and sleep is possible; and 3 = severe itching, normal daily activity and sleep is impaired. The maximum score is 42.
Time frame: Day 28
Population: ITT = 73
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Miltefosine | Urticaria Activity Score (% Change From Baseline) | -25.5 percentage of UAS baseline | Standard Deviation 38.2 |
| Placebo | Urticaria Activity Score (% Change From Baseline) | -10.1 percentage of UAS baseline | Standard Deviation 33.4 |