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

October 7, 2021 updated by: Novartis Pharmaceuticals

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)

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

293

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria, A 1090
        • Novartis Investigative Site
  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • Canada
    • Ontario
      • Markham, Ontario, Canada, L3P 1A8
        • Novartis Investigative Site
      • New Market, Ontario, Canada, L3Y 5G8
        • Novartis Investigative Site
      • Toronto, Ontario, Canada, M4V 1R2
        • Novartis Investigative Site
      • Waterloo, Ontario, Canada, N2J 1C4
        • Novartis Investigative Site
    • Quebec
      • Sainte-Hyacinthe, Quebec, Canada, J2S 66
        • Novartis Investigative Site
  • Czechia
      • Praha 10, Czechia, 100 00
        • Novartis Investigative Site
    • Czech Republic
      • Karlovy Vary, Czech Republic, Czechia, 36001
        • Novartis Investigative Site
      • Novy Jicin, Czech Republic, Czechia, 74101
        • Novartis Investigative Site
    • Prague 1
      • Prague, Prague 1, Czechia, 11000
        • Novartis Investigative Site
  • Finland
      • Helsinki, Finland, 00250
        • Novartis Investigative Site
      • Tampere, Finland, 33520
        • Novartis Investigative Site
      • Turku, Finland, 20520
        • Novartis Investigative Site
  • Germany
      • Bielefeld, Germany, 33647
        • Novartis Investigative Site
      • Braunschweig, Germany, 38100
        • Novartis Investigative Site
      • Frankfurt, Germany, 60590
        • Novartis Investigative Site
      • Gera, Germany, 07548
        • Novartis Investigative Site
      • Halle (Saale), Germany, 06108
        • Novartis Investigative Site
      • Hamburg, Germany, 20537
        • Novartis Investigative Site
      • Hamburg, Germany, 22391
        • Novartis Investigative Site
      • Hannover, Germany, 30625
        • Novartis Investigative Site
      • Heidelberg, Germany, 69120
        • Novartis Investigative Site
      • Memmingen, Germany, 87700
        • Novartis Investigative Site
      • Muenchen, Germany, 80337
        • Novartis Investigative Site
      • Muenster, Germany, 48149
        • Novartis Investigative Site
      • Osnabrueck, Germany, 49074
        • Novartis Investigative Site
  • Hungary
      • Debrecen, Hungary, 4032
        • Novartis Investigative Site
  • Iceland
      • Kopavogur, Iceland, 201
        • Novartis Investigative Site
  • Japan
      • Fukuoka, Japan, 819 0167
        • Novartis Investigative Site
      • Fukuoka, Japan, 819-0373
        • Novartis Investigative Site
      • Kyoto, Japan, 606 8507
        • Novartis Investigative Site
      • Tokyo, Japan, 158 0097
        • Novartis Investigative Site
    • Aichi
      • Nagoya-city, Aichi, Japan, 467-8602
        • Novartis Investigative Site
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 060-0063
        • Novartis Investigative Site
    • Hyogo
      • Kobe, Hyogo, Japan, 654 0011
        • Novartis Investigative Site
    • Kanagawa
      • Yokohama, Kanagawa, Japan, 220-6208
        • Novartis Investigative Site
      • Yokohama, Kanagawa, Japan, 221-0825
        • Novartis Investigative Site
    • Osaka
      • Sakai, Osaka, Japan, 593-8324
        • Novartis Investigative Site
    • Tokyo
      • Shinagawa ku, Tokyo, Japan, 141 8625
        • Novartis Investigative Site
      • Shinjuku ku, Tokyo, Japan, 162 8655
        • Novartis Investigative Site
      • Shinjuku-ku, Tokyo, Japan, 160-0023
        • Novartis Investigative Site
  • Netherlands
      • Bergen op Zoom, Netherlands, 4624 VT
        • Novartis Investigative Site
      • Breda, Netherlands, 4818 CK
        • Novartis Investigative Site
      • Groningen, Netherlands, 9713 GZ
        • Novartis Investigative Site
      • Rotterdam, Netherlands, 3015 CE
        • Novartis Investigative Site
  • Poland
      • Katowice, Poland, 40-648
        • Novartis Investigative Site
      • Rzeszow, Poland, 35 055
        • Novartis Investigative Site
      • Warszawa, Poland, 04141
        • Novartis Investigative Site
    • Mazowian
      • Warszawa, Mazowian, Poland, 02 495
        • Novartis Investigative Site
  • Russian Federation
      • Chelyabinsk, Russian Federation, 454092
        • Novartis Investigative Site
      • Ekaterinburg, Russian Federation, 620023
        • Novartis Investigative Site
      • Kazan, Russian Federation, 420012
        • Novartis Investigative Site
      • Krasnodar, Russian Federation, 350020
        • Novartis Investigative Site
      • Moscow, Russian Federation, 123182
        • Novartis Investigative Site
      • Petrozavodsk, Russian Federation, 185019
        • Novartis Investigative Site
      • Saint Petersburg, Russian Federation, 191123
        • Novartis Investigative Site
      • Saint-Petersburg, Russian Federation, 196143
        • Novartis Investigative Site
      • Smolensk, Russian Federation, 214019
        • Novartis Investigative Site
      • St Petersburg, Russian Federation, 192007
        • Novartis Investigative Site
      • St Petersburg, Russian Federation, 197136
        • Novartis Investigative Site
      • St Petersburg, Russian Federation, 194325
        • Novartis Investigative Site
      • St Petersburg, Russian Federation, 194223
        • Novartis Investigative Site
      • St.Petersburg, Russian Federation, 196240
        • Novartis Investigative Site
      • Stavropol, Russian Federation, 355020
        • Novartis Investigative Site
      • Yekaterinburg, Russian Federation, 620109
        • Novartis Investigative Site
  • Slovakia
      • Bratislava, Slovakia, 85101
        • Novartis Investigative Site
      • Levice, Slovakia, 934 01
        • Novartis Investigative Site
      • Svidnik, Slovakia, 08901
        • Novartis Investigative Site
    • SVK
      • Bardejov, SVK, Slovakia, 085 01
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Novartis Investigative Site
    • Taiwan ROC
      • Taichung, Taiwan ROC, Taiwan, 40201
        • Novartis Investigative Site
  • United Kingdom
      • Liverpool, United Kingdom, L14 3PE
        • Novartis Investigative Site
      • London, United Kingdom, SE1 9RT
        • Novartis Investigative Site
      • Portsmouth, United Kingdom, PO3 6AD
        • Novartis Investigative Site
    • Devon
      • Plymouth, Devon, United Kingdom, PL6 8DH
        • Novartis Investigative Site
    • West Midlands
      • Dudley, West Midlands, United Kingdom, DY1 2HQ
        • Novartis Investigative Site
  • United States
    • Arizona
      • Litchfield Park, Arizona, United States, 85340
        • Novartis Investigative Site
    • California
      • Fountain Valley, California, United States, 92708
        • Novartis Investigative Site
      • San Diego, California, United States, 92123
        • Novartis Investigative Site
      • San Diego, California, United States, 92103
        • Novartis Investigative Site
    • Florida
      • Tampa, Florida, United States, 33612
        • Novartis Investigative Site
      • Tampa, Florida, United States, 33609
        • Novartis Investigative Site
    • Kentucky
      • Louisville, Kentucky, United States, 40217
        • Novartis Investigative Site
    • Ohio
      • Cincinnati, Ohio, United States, 45231
        • Novartis Investigative Site
      • Fairborn, Ohio, United States, 45324
        • Novartis Investigative Site
    • South Carolina
      • Greer, South Carolina, United States, 29651
        • Novartis Investigative Site
    • Texas
      • Houston, Texas, United States, 77004
        • Novartis Investigative Site
    • Utah
      • West Jordan, Utah, United States, 84088
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: placebo
Placebo
Drug: Placebo
once daily from baseline until week 16
EXPERIMENTAL: ZPL389 3mg
ZPL389 3 mg oral powder
Drug: ZPL389 3mg
ZPL389 3 mg oral powder; once daily from baseline to week 16
EXPERIMENTAL: ZPL389 10 mg
ZPL389 10 mg oral powder
Drug: ZPL389 10mg
ZPL389 10 mg oral powder; once daily from baseline to week 16
EXPERIMENTAL: ZPL389 30mg
ZPL389 30 mg oral powder
Drug: ZPL389 30mg
ZPL389 30 mg oral powder; once daily from baseline to week 16
EXPERIMENTAL: ZPL389 50mg
ZPL389 50 mg oral powder
Drug: ZPL389 50mg
ZPL389 50 mg oral powder; once daily from baseline to week 16

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of IGA Responders at Week 16
Time Frame: 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change From Baseline in EASI Score at Week 16
Time Frame: Baseline, 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
Percent Change From Baseline in EASI Score Over Time
Time Frame: Baseline, Week 2, Week 4, Week 6, Week 8, Week 12
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
Percentage of EASI50 Responders Over Time
Time Frame: Week 2, Week 4, Week 6, Week 8, Week 12, 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.

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
Percentage of EASI75 Responders Over Time
Time Frame: Week 2, Week 4, Week 6, Week 8, Week 12, 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.

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
Percentage of IGA Responders Over Time
Time Frame: Week 2, Week 4, Week 6, Week 8, Week 12

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
Number of Patients With Adverse Events
Time Frame: Up to week 20
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 14, 2018

Primary Completion (ACTUAL)

July 15, 2020

Study Completion (ACTUAL)

August 6, 2020

Study Registration Dates

First Submitted

March 27, 2018

First Submitted That Met QC Criteria

April 24, 2018

First Posted (ACTUAL)

May 7, 2018

Study Record Updates

Last Update Posted (ACTUAL)

October 8, 2021

Last Update Submitted That Met QC Criteria

October 7, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CZPL389A2203

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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