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A Study to Assess the Safety and Efficacy of ZPL389 With TCS/TCI in Atopic Dermatitis Patients (ZESTExt)

Primary Purpose

Atopic Dermatitis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ZPL389 30mg
ZPL389 50mg
TCS and/or TCI
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atopic Dermatitis focused on measuring atopic dermatitis, AD, eczema, itch, pruritus, H4R, ZPL389

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must give a written, signed and dated informed consent
  • Subjects with atopic dermatitis who have participated in and completed 16 weeks of treatment in CZPL389A2203 study.
  • Willing and able to comply with scheduled visits, treatment plan, laboratory tests, diary completion and other study procedures.

Exclusion Criteria:

  • Inability to use TCS and/or TCI due to history of important side effects of topical medication (e.g., intolerance or hypersensitivity reactions).
  • Treatment discontinued subject from CZPL389A2203 study.
  • Any skin disease that would confound the diagnosis or evaluation of atopic dermatitis disease activity.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

ZPL389 30mg

ZPL389 50mg

Arm Description

30mg of ZPL389 + TCS and/or TCI for patients re-randomized from the core study (received placebo/ZPL389 3mg/ 10mg in the core study) and for patients continuing in the same arm from the core study

50mg of ZPL389 + TCS and/or TCI for patients re-randomized from the core study (received placebo/ZPL389 3mg/ 10mg in the core study) and for patients continuing in the same arm from the core study

Outcomes

Primary Outcome Measures

Number of Patients With Adverse Events in the First 16 Weeks of This Extension Study
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. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis.
Number of Patients With Adverse Events After 16 Weeks of Treatment in This Extension Study
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. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis.

Secondary Outcome Measures

Percentage of Investigator's Global Assessment (IGA) Responders Over Time
IGA score is used to determine the severity of atopic dermatitis symptoms and clinical response to treatment. The scale ranges from 0=clear to 4=severe. It is a static scale and doesn't refer to previous status of the subject. IGA response is an achievement of an IGA score of 0 or 1 with a 2-point reduction from baseline without use of confounding therapy up to the assessment time point. Treatment discontinuations for lack of efficacy or AE are considered non-responders.Presentation of the results is stratified by if patients were re-randomized from the core study or not. As all patients were rolling over from the core study, in addition to the timeframe referring to the start in this extension study, the timeframe corresponding to the start in the core study (+16 weeks) are provided in parenthesis. 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.
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. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Presentation of the results is stratified by if patients were re-randomized from the core study or not. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis. 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.
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 a reduction from baseline of ≥ 75% in EASI score. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Presentation of the results is stratified by if patients were re-randomized from the core study or not. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis. 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.

Full Information

First Posted
April 4, 2019
Last Updated
October 7, 2021
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03948334
Brief Title
A Study to Assess the Safety and Efficacy of ZPL389 With TCS/TCI in Atopic Dermatitis Patients
Acronym
ZESTExt
Official Title
A Randomized, Double Blind, Multicenter Extension to CZPL389A2203 Dose-ranging Study to Assess the Short-term and Long-term Safety and Efficacy of Oral ZPL389 With Concomitant Use of TCS and/or TCI in Adult Patients With Atopic Dermatitis.
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Core terminated due to lack of efficacy
Study Start Date
April 4, 2019 (Actual)
Primary Completion Date
July 23, 2020 (Actual)
Study Completion Date
August 25, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This extension study (CZPL389A2203E1) was designed as a 2-year (100 weeks) extension to the core study (CZPL389A2203/ NCT03517566) which is disclosed separately. It aimed to assess the short-term and long-term safety of (blinded) 30 mg o.d and 50 mg o.d ZPL389 with concomitant or intermittent use of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI).
Detailed Description
Subjects who had received ZPL389 30 mg or 50 mg doses in the core study (CZPL389A2203), continued to receive the same doses in double-blinded fashion. Subjects who had received ZPL389 3 mg, 10 mg or placebo in the core study were randomized to 30 mg or 50 mg ZPL389 in a 1:1 ratio. All subjects received concomitant or intermittent TCS and/or TCI along with ZPL389. Short-term safety was assessed up to week 16 of this extension study (week 16 to week 32 referring to the start of core study treatment) and long-term safety was assessed after week 16 of this extension study (after week 32 referring to the start of core study treatment). The entire planned time frame (100 weeks) was not assessed as originally planned due to early termination of the core and extension studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
Keywords
atopic dermatitis, AD, eczema, itch, pruritus, H4R, ZPL389

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
123 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ZPL389 30mg
Arm Type
Experimental
Arm Description
30mg of ZPL389 + TCS and/or TCI for patients re-randomized from the core study (received placebo/ZPL389 3mg/ 10mg in the core study) and for patients continuing in the same arm from the core study
Arm Title
ZPL389 50mg
Arm Type
Experimental
Arm Description
50mg of ZPL389 + TCS and/or TCI for patients re-randomized from the core study (received placebo/ZPL389 3mg/ 10mg in the core study) and for patients continuing in the same arm from the core study
Intervention Type
Drug
Intervention Name(s)
ZPL389 30mg
Intervention Description
30mg of ZPL389; once daily
Intervention Type
Drug
Intervention Name(s)
ZPL389 50mg
Intervention Description
50mg of ZPL389; once daily
Intervention Type
Drug
Intervention Name(s)
TCS and/or TCI
Intervention Description
Topical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity.
Primary Outcome Measure Information:
Title
Number of Patients With Adverse Events in the First 16 Weeks of This Extension Study
Description
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. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis.
Time Frame
16 weeks (week 16 to week 32 referring to core study)
Title
Number of Patients With Adverse Events After 16 Weeks of Treatment in This Extension Study
Description
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. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis.
Time Frame
From week 16 to week 67 of this extension study (week 32 to week 83 referring to core study)
Secondary Outcome Measure Information:
Title
Percentage of Investigator's Global Assessment (IGA) Responders Over Time
Description
IGA score is used to determine the severity of atopic dermatitis symptoms and clinical response to treatment. The scale ranges from 0=clear to 4=severe. It is a static scale and doesn't refer to previous status of the subject. IGA response is an achievement of an IGA score of 0 or 1 with a 2-point reduction from baseline without use of confounding therapy up to the assessment time point. Treatment discontinuations for lack of efficacy or AE are considered non-responders.Presentation of the results is stratified by if patients were re-randomized from the core study or not. As all patients were rolling over from the core study, in addition to the timeframe referring to the start in this extension study, the timeframe corresponding to the start in the core study (+16 weeks) are provided in parenthesis. 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.
Time Frame
Week 4, Week 8, Week 12, Week 16, Week 28, Week 40 (Week 20, Week 24, Week 28 ,Week 32, Week 44, Week 56 referring to core study)
Title
Percentage of EASI50 Responders Over Time
Description
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. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Presentation of the results is stratified by if patients were re-randomized from the core study or not. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis. 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.
Time Frame
Week 4, Week 8, Week 12, Week 16, Week 28, Week 40 (Week 20, Week 24, Week 28 ,Week 32, Week 44, Week 56 referring to core study)
Title
Percentage of EASI75 Responders Over Time
Description
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 a reduction from baseline of ≥ 75% in EASI score. Treatment discontinuations for lack of efficacy or adverse event are considered non-responders. Presentation of the results is stratified by if patients were re-randomized from the core study or not. As all patients were rolling over from the core study CZPL389A2203, in addition to the time frame referring to the start in this extension study, the time frame corresponding to the start in the core study (+16 weeks) are provided in parenthesis. 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.
Time Frame
Week 4, Week 8, Week 12, Week 16, Week 28, Week 40 (Week 20, Week 24, Week 28 ,Week 32, Week 44, Week 56 referring to core study)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must give a written, signed and dated informed consent Subjects with atopic dermatitis who have participated in and completed 16 weeks of treatment in CZPL389A2203 study. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, diary completion and other study procedures. Exclusion Criteria: Inability to use TCS and/or TCI due to history of important side effects of topical medication (e.g., intolerance or hypersensitivity reactions). Treatment discontinued subject from CZPL389A2203 study. Any skin disease that would confound the diagnosis or evaluation of atopic dermatitis disease activity.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Litchfield Park
State/Province
Arizona
ZIP/Postal Code
85340
Country
United States
Facility Name
Novartis Investigative Site
City
Fairborn
State/Province
Ohio
ZIP/Postal Code
45324
Country
United States
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4V 1R2
Country
Canada
Facility Name
Novartis Investigative Site
City
Helsinki
ZIP/Postal Code
00250
Country
Finland
Facility Name
Novartis Investigative Site
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Novartis Investigative Site
City
Bielefeld
ZIP/Postal Code
33647
Country
Germany
Facility Name
Novartis Investigative Site
City
Gera
ZIP/Postal Code
07548
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20537
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
22391
Country
Germany
Facility Name
Novartis Investigative Site
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Memmingen
ZIP/Postal Code
87700
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenchen
ZIP/Postal Code
80337
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Novartis Investigative Site
City
Osnabrueck
ZIP/Postal Code
49074
Country
Germany
Facility Name
Novartis Investigative Site
City
Kopavogur
ZIP/Postal Code
201
Country
Iceland
Facility Name
Novartis Investigative Site
City
Nagoya-city
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-0063
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
220-6208
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
221-0825
Country
Japan
Facility Name
Novartis Investigative Site
City
Sakai
State/Province
Osaka
ZIP/Postal Code
593-8324
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku ku
State/Province
Tokyo
ZIP/Postal Code
162 8655
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka
ZIP/Postal Code
819 0167
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka
ZIP/Postal Code
819-0373
Country
Japan
Facility Name
Novartis Investigative Site
City
Kyoto
ZIP/Postal Code
606 8507
Country
Japan
Facility Name
Novartis Investigative Site
City
Tokyo
ZIP/Postal Code
158 0097
Country
Japan
Facility Name
Novartis Investigative Site
City
Breda
State/Province
CK
ZIP/Postal Code
4818
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Bergen op Zoom
ZIP/Postal Code
4624 VT
Country
Netherlands
Facility Name
Novartis Investigative Site
City
Warszawa
State/Province
Mazowian
ZIP/Postal Code
02 495
Country
Poland
Facility Name
Novartis Investigative Site
City
Rzeszow
ZIP/Postal Code
35 055
Country
Poland
Facility Name
Novartis Investigative Site
City
Warszawa
ZIP/Postal Code
04141
Country
Poland
Facility Name
Novartis Investigative Site
City
Chelyabinsk
ZIP/Postal Code
454092
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Kazan
ZIP/Postal Code
420012
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Moscow
ZIP/Postal Code
123182
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
191123
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint Petersburg
ZIP/Postal Code
194354
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Saint-Petersburg
ZIP/Postal Code
196143
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Smolensk
ZIP/Postal Code
214019
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Bardejov
State/Province
SVK
ZIP/Postal Code
085 01
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Bratislava
ZIP/Postal Code
85101
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Levice
ZIP/Postal Code
934 01
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Svidnik
ZIP/Postal Code
08901
Country
Slovakia
Facility Name
Novartis Investigative Site
City
Taichung
State/Province
Taiwan ROC
ZIP/Postal Code
40201
Country
Taiwan
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Portsmouth
ZIP/Postal Code
PO6 6AD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect 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
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=725
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

A Study to Assess the Safety and Efficacy of ZPL389 With TCS/TCI in Atopic Dermatitis Patients

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