A Study to Assess the Safety and Efficacy of ZPL389 in Patients With Moderate to Severe Atopic Dermatitis

Atopic Dermatitis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Multicenter Dose Ranging Study to Assess the Safety and Efficacy of Multiple Oral ZPL389 Doses in Patients With Moderate to Severe Atopic Dermatitis (ZEST Trial)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03517566
• Other study ID #: CZPL389A2203
• Status: Terminated
• Phase: Phase 2
• Start date: November 14, 2018
• Est. completion date: August 6, 2020

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a randomized, double-blind, placebo-controlled, parallel-group study to assess safety and efficacy of ZPL389 in subjects with moderate to severe atopic dermatitis with a total study duration up to 24 weeks

Description:

A screening period of up to 4 weeks was followed by a 16-week double blinded treatment period. After the end of treatment visit, subjects were offered the possibility of ongoing treatment in the extension study (CZPL389A2203E1/ NCT03948334), or of entering the 4 week treatment-free follow-up period.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 293
• Est. completion date: August 6, 2020
• Est. primary completion date: July 15, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must give a written, signed and dated informed consent
• Chronic atopic dermatitis present for at least 1 year before Baseline
• Moderate to severe atopic dermatitis defined as per EASI, IGA and BSA.
• 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
• Candidate for systemic treatment

Exclusion Criteria:

• Any skin disease that would confound the diagnosis or evaluation of atopic dermatitis disease activity
• Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.
• History of hypersensitivity to any of the study drug constituents or to drugs of similar chemical classes.
• Participation in prior ZPL389 studies

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• Placebo
once daily from baseline until week 16
• ZPL389 3mg
ZPL389 3 mg oral powder; once daily from baseline to week 16
• ZPL389 10mg
ZPL389 10 mg oral powder; once daily from baseline to week 16
• ZPL389 30mg
ZPL389 30 mg oral powder; once daily from baseline to week 16
• ZPL389 50mg
ZPL389 50 mg oral powder; once daily from baseline to week 16

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Markham	Ontario
Canada	Novartis Investigative Site	New Market	Ontario
Canada	Novartis Investigative Site	Sainte-Hyacinthe	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Waterloo	Ontario
Czechia	Novartis Investigative Site	Karlovy Vary	Czech Republic
Czechia	Novartis Investigative Site	Novy Jicin	Czech Republic
Czechia	Novartis Investigative Site	Prague	Prague 1
Czechia	Novartis Investigative Site	Praha 10
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Turku
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Braunschweig
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Halle (Saale)
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Memmingen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Osnabrueck
Hungary	Novartis Investigative Site	Debrecen
Iceland	Novartis Investigative Site	Kopavogur
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Kobe	Hyogo
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Sakai	Osaka
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Shinagawa ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Tokyo
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Netherlands	Novartis Investigative Site	Bergen op Zoom
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Groningen
Netherlands	Novartis Investigative Site	Rotterdam
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa	Mazowian
Russian Federation	Novartis Investigative Site	Chelyabinsk
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Krasnodar
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Petrozavodsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St.Petersburg
Russian Federation	Novartis Investigative Site	Stavropol
Russian Federation	Novartis Investigative Site	Yekaterinburg
Slovakia	Novartis Investigative Site	Bardejov	SVK
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Levice
Slovakia	Novartis Investigative Site	Svidnik
Taiwan	Novartis Investigative Site	Taichung	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Dudley	West Midlands
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Plymouth	Devon
United Kingdom	Novartis Investigative Site	Portsmouth
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Fairborn	Ohio
United States	Novartis Investigative Site	Fountain Valley	California
United States	Novartis Investigative Site	Greer	South Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Litchfield Park	Arizona
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Czechia,  Finland,  Germany,  Hungary,  Iceland,  Japan,  Netherlands,  Poland,  Russian Federation,  Slovakia,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of IGA Responders at Week 16	Investigator's Global Assessment (IGA) score is used to determine the severity of atopic dermatitis symptoms and clinical response to treatment. It reflects a subject's overall disease severity for the whole body. The scale includes 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. It is a static scale and does not refer to previous status of the subject.; IGA response is defined as achievement of an IGA score of 0 or 1 with a 2-point reduction from baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point.; Treatment discontinuations for lack of efficacy or adverse event are considered non-responders.; Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline IGA as covariates.	Week 16
Secondary	Percent Change From Baseline in EASI Score at Week 16	Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema.	Baseline, Week 16
Secondary	Percent Change From Baseline in EASI Score Over Time	Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema.	Baseline, Week 2, Week 4, Week 6, Week 8, Week 12
Secondary	Percentage of EASI50 Responders Over Time	Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema.; EASI50 response is defined as achieving = 50% improvement (reduction) in EASI score compared to baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point.; Treatment discontinuations for lack of efficacy or adverse event are considered non-responders.; Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline EASI as covariates	Week 2, Week 4, Week 6, Week 8, Week 12, Week 16
Secondary	Percentage of EASI75 Responders Over Time	Eczema Area and Severity Index (EASI) is used to assess the extend and severity of atopic dermatitis on a scale from 0 to 72 where 72 is worst eczema.; EASI75 response is defined as achieving = 75% improvement (reduction) in EASI score compared to baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point.; Treatment discontinuations for lack of efficacy or adverse event are considered non-responders.; Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline EASI as covariates	Week 2, Week 4, Week 6, Week 8, Week 12, Week 16
Secondary	Percentage of IGA Responders Over Time	Investigator's Global Assessment (IGA) score is used to determine the severity of atopic dermatitis symptoms and clinical response to treatment. It reflects a subject's overall disease severity for the whole body. The scale includes 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe. It is a static scale and does not refer to previous status of the subject.; IGA response is defined as achievement of an IGA score of 0 or 1 with a 2-point reduction from baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point.; Treatment discontinuations for lack of efficacy or adverse event are considered non-responders.; Percentage of responders was calculated based on a logistic regression model with response as outcome variable and treatment (dose as categorical variable) and baseline IGA as covariates.	Week 2, Week 4, Week 6, Week 8, Week 12
Secondary	Number of Patients With Adverse Events	An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study until the end of study visit. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.	Up to week 20

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com