A study to assess the safety and efficacy of ZPL389 doses in subjects with moderate to severe atopic dermatitis
- Conditions
- Moderate to severe atopic dermatitisMedDRA version: 20.0Level: LLTClassification code 10003639Term: Atopic dermatitisSystem Organ Class: 100000004858Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2017-002176-75-DE
- Lead Sponsor
- ovartis Pharma AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 360
Eligible for inclusion in this study must fulfill all of the following criteria:
- Written informed consent
- 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 =16 at Screening and =16 at Baseline
? - Investigator's global assessment 3 or 4 on a 5-point scale (at screening and Baseline
? - Body Surface Area involvement =10% at Screening and Baseline
- Average peak pruritis 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 or for whom topical treatments are otherwise medically inadvisable (e.g., because of important side effects or safety risks)
- Candidate for systemic treatment
- Have applied a stable dose of bland topical emollient at least twice daily for at least the 7 consecutive days immediately before the baseline visit
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
- Any skin disease that, in the opinion of the investigator, including infection, would confound the diagnosis or evaluation of atopic dermatitis disease activity
- Current skin infection
- Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days /until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
- History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.
- subjects taking prohibited medication as per protocol
- Risk factors for Torsades de Pointe including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia or any of the following:
? - Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
? - Concomitant medication(s) with a Known Risk of Torsades de Pointe” that cannot be discontinued or replaced by safe alternative medication.
- 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 or subjects with factors that increase susceptibility to DILI
- Subjects who have a laboratory abnormality at Screening
- History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years
- Past medical history record of, or current infection with, human immunodeficiency virus
- Any surgical, medical, psychiatric or additional physical condition that the Investigator feels may jeopardize the subject in case of participation in this study
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using required methods of contraception during dosing and for 4 weeks after stopping of investigational medication.
- Sexually active males unless they use a condom during intercourse while taking drug and for 120 days after stopping investigational medication and should not father a child in this period.
- Prior exposure to ZPL389 treatment
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To characterize the dose-response relationship of ZPL389 in patients with moderate to severe AD assessed by Investigator's global assessment (IGA) response at week 16 .;Secondary Objective: • To characterize the dose-response relationship of ZPL389 in patients 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<br>• To evaluate the efficacy across different dose levels as assessed by EASI and IGA compared to placebo over time<br>• To assess the safety and tolerability of different doses of ZPL389 as compared to placebo;Primary end point(s): To characterize the dose-response relationship of ZPL389 in patients with moderate to severe AD assessed by Investigator's global assessment (IGA) response after 16 weeks of treatment;Timepoint(s) of evaluation of this end point: IGA response at Week 16
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • To characterize the dose-response relationship of ZPL389 in patients 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<br>• To evaluate the efficacy across different dose levels as assessed by EASI and IGA compared to placebo over time<br>• To assess the safety and tolerability of different doses of ZPL389 as compared to placebo;Timepoint(s) of evaluation of this end point: • Percent change from baseline EASI score at Week 16<br>• At each visit: <br> • IGA score<br> • IGA response<br> • EASI score as well as absolute and percent change from baseline EASI score<br> • EASI 50 response, EASI 75 response<br>• Frequency of adverse events