In this study we want to evaluate the safety and efficacy of the new drug ZPL389. ZPL389 is tested in various strengths in patients with moderate or severe atopic dermatitis. The effects of ZPL389 are compared with those of a placebo.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To characterize the dose-response relationship of ZPL389 in subjects with
moderate to severe AD assessed by IGA response after 16 weeks of treatment
Secondary outcome
- To characterize the dose-response relationship of ZPL389 in subjects with
moderate to severe AD assessed using the percent change from
Baseline in Eczema Area and Severity Index (EASI) score after 16 weeks of
treatment
- To evaluate the efficacy across different dose levels as assessed by EASI and
IGA compared to placebo over time
- To assess the safety and tolerability of different doses of ZPL389 as
compared to placebo
Background summary
Atopic dermatitis is also called atopic eczema. It is a form of skin
inflammation. Symptoms include itching, redness and swelling of the skin. The
skin spots can be moist and may have scabs on it. Two to ten percent of the
adults and up to 20 percent of the children have AD, of which about 70% and 16%
are moderate to severe. The usual treatment of AD consists of moisturizing
cream, anti-inflammatory ointment (eg with corticosteroids), light therapy and
anti-inflammatory pills ". Unfortunately, some of the patients have
insufficient benefit from these existing treatments or can not tolerate them
well. There is therefore a need for new medicines.
ZPL389 is a substance that attaches to a body protein called the histamine 4
receptor (H4R). Histamine is made by the body when it comes into contact with a
substance for which it is hypersensitive. Histamine attaches itself to the H4R
and therefore causes skin symptoms such as itching. ZPL389 is so firmly
attached to the H4R that histamine can no longer attach itself to it. We
therefore expect that ZPL389 can counteract the symptoms of atopic dermatitis.
So far, around 214 test subjects have been treated with ZPL389 in studies.
Study objective
In this study we want to evaluate the safety and efficacy of the new drug
ZPL389. ZPL389 is tested in various strengths in patients with moderate or
severe atopic dermatitis. The effects of ZPL389 are compared with those of a
placebo.
Study design
This is a randomized, double-blind, placebo-controlled, multicenter dose
ranging (5 parallel groups) study in at least
360 subjects with moderate to severe Atopic Dermatitis. An unbalanced
randomization ratio will be used to randomize approximately 90 patients in the
30 mg / day, 50 mg / day and placebo arms. Approximately 45 patients will be
randomized in the 3 mg / day and 10 mg / day arms.
The study consists of a screening period of 1 to 3 weeks (depending on current
medication use and associated wash-out period) and a 16-week double-blind
treatment period. After the end of treatment visit, subjects may be offered
ongoing treatment in an
extension study, or enter the 4 week treatment-free follow up period.
The total duration of study is a maximum of 23 weeks. Subjects can participate
in an extension study. Details of this extention study will be described in a
separate pro
Intervention
Four dose levels were chosen to characterize the dose-response curve. An
unbalanced allocation of 2:1:1:2:2 for placebo: 3 mg: 10 mg: 30 mg: 50 mg with
more subjects on placebo and the higher doses of ZPL389 is chosen to increase
the precision of the estimate for the treatment effect at doses in the expected
efficacious dose range.
Study burden and risks
The study lasts for a maximum of 24 weeks (almost half a year). The study
consists of screening from 1 to 4 weeks, a treatment period of 16 weeks and a
follow-up period of 4 weeks.
Based on 9 visits:
- Physical examination: 9x
- ECG: 9x
- Vital signs: 9x
- Blood test (9-27 ml): 9x
- Pregnancy test (if applicable) 7x
- Urine test: 9x
- Diary completion: daily
- Complete questionnaires: 6x
Optional:
- Measuring sleeping activity: every night during 1 week preceding 6 visits
- Farmacogenetics (1x bloodsdample collection)
- Tape-strips (3 visits)
Side effects of research medication and inconveniences research procedures.
There is banned comedication.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
- Females and males aged 18 years or older
- Chronic atopic dermatitis (according to AADConsensus Criteria), that has been present for at least 1 year before the Baseline visit.
- Moderate to severe atopic dermatitis defined as:
- Eczema Area and Severity Index (EASI) >=16 at Screening and Baseline
- IGA 3 or 4 at Screening and Baseline
- Body Surface Area involvement >=10% at Screening and Baseline
- Average peak pruritus score >=3 as assessed by NRS over the last 7 days prior to Baseline
- Documented recent history (within 6 months before the screening visit) of inadequate
response to treatment with topical medications for AD or for whom topical treatments are
otherwise medically inadvisable
- Have applied a stable dose of bland topical emollient once daily for at least the 7 consecutive days immediately before the baseline visit
Exclusion criteria
- Any skin disease that, in the opinion of the investigator, would confound the diagnosis or
evaluation of AD disease activity
- Risk factors for Torsades de Pointes (TdP)
- Resting QTcF >=450 msec (male) or >=470 msec (female) at Screening or Baseline or inability to determine the QTcF interval
- Cardiac or cardiac repolarization abnormality
- Subjects with pre-existing conditions that may confound ability to diagnose drug-induced
liver injury (DILI) or subjects with factors that increase susceptibility to DILI
- Subjects who have a laboratory abnormality at Screening as follows:
- ALT/AST, ALP or TBL above upper limit of normal (ULN)
- Total white blood cell count (WBC) <2.5 x 109cells/L
- Absolute neutrophil count (ANC) <1.5 x 109/L (one re-test is allowed during the screening period)
- Hemoglobin <11.0 g/dL
- Platelets <100.0 x 109/L
- Potassium and magnesium outside normal range
- eGFR by MDR equation <60 mL/minute/1.73 m2
- Past medical history record of, or current infection with, human immunodeficiency virus (HIV)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-002176-75-NL |
| ClinicalTrials.gov | NCT03517566 |
| CCMO | NL63968.078.18 |