We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03948334
Recruitment Status : Terminated (Core terminated due to lack of efficacy)
First Posted : May 13, 2019
Results First Posted : July 20, 2021
Last Update Posted : October 8, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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).

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Drug: ZPL389 30mg Drug: ZPL389 50mg Drug: TCS and/or TCI Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 123 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : April 4, 2019
Actual Primary Completion Date : July 23, 2020
Actual Study Completion Date : August 25, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: ZPL389 30mg
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
Drug: ZPL389 30mg
30mg of ZPL389; once daily

Drug: TCS and/or TCI
Topical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity.

Experimental: ZPL389 50mg
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
Drug: ZPL389 50mg
50mg of ZPL389; once daily

Drug: TCS and/or TCI
Topical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity.




Primary Outcome Measures :
  1. Number of Patients With Adverse Events in the First 16 Weeks of This Extension Study [ Time Frame: 16 weeks (week 16 to week 32 referring to core 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.


  2. Number of Patients With Adverse Events After 16 Weeks of Treatment in This Extension Study [ Time Frame: From week 16 to week 67 of this extension study (week 32 to week 83 referring to core 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 :
  1. Percentage of Investigator's Global Assessment (IGA) Responders Over Time [ 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) ]
    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.

  2. Percentage of EASI50 Responders Over Time [ 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) ]

    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.


  3. Percentage of EASI75 Responders Over Time [ 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) ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03948334


Locations
Layout table for location information
United States, Arizona
Novartis Investigative Site
Litchfield Park, Arizona, United States, 85340
United States, Ohio
Novartis Investigative Site
Fairborn, Ohio, United States, 45324
Belgium
Novartis Investigative Site
Leuven, Belgium, 3000
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M4V 1R2
Finland
Novartis Investigative Site
Helsinki, Finland, 00250
Novartis Investigative Site
Turku, Finland, 20520
Germany
Novartis Investigative Site
Bielefeld, Germany, 33647
Novartis Investigative Site
Gera, Germany, 07548
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
Iceland
Novartis Investigative Site
Kopavogur, Iceland, 201
Japan
Novartis Investigative Site
Nagoya-city, Aichi, Japan, 467-8602
Novartis Investigative Site
Sapporo, Hokkaido, Japan, 060-0063
Novartis Investigative Site
Yokohama, Kanagawa, Japan, 220-6208
Novartis Investigative Site
Yokohama, Kanagawa, Japan, 221-0825
Novartis Investigative Site
Sakai, Osaka, Japan, 593-8324
Novartis Investigative Site
Shinjuku ku, Tokyo, Japan, 162 8655
Novartis Investigative Site
Shinjuku-ku, Tokyo, Japan, 160-0023
Novartis Investigative Site
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
Netherlands
Novartis Investigative Site
Breda, CK, Netherlands, 4818
Novartis Investigative Site
Bergen op Zoom, Netherlands, 4624 VT
Poland
Novartis Investigative Site
Warszawa, Mazowian, Poland, 02 495
Novartis Investigative Site
Rzeszow, Poland, 35 055
Novartis Investigative Site
Warszawa, Poland, 04141
Russian Federation
Novartis Investigative Site
Chelyabinsk, Russian Federation, 454092
Novartis Investigative Site
Kazan, Russian Federation, 420012
Novartis Investigative Site
Moscow, Russian Federation, 123182
Novartis Investigative Site
Saint Petersburg, Russian Federation, 191123
Novartis Investigative Site
Saint Petersburg, Russian Federation, 194354
Novartis Investigative Site
Saint-Petersburg, Russian Federation, 196143
Novartis Investigative Site
Smolensk, Russian Federation, 214019
Slovakia
Novartis Investigative Site
Bardejov, SVK, Slovakia, 085 01
Novartis Investigative Site
Bratislava, Slovakia, 85101
Novartis Investigative Site
Levice, Slovakia, 934 01
Novartis Investigative Site
Svidnik, Slovakia, 08901
Taiwan
Novartis Investigative Site
Taichung, Taiwan ROC, Taiwan, 40201
Novartis Investigative Site
Taipei, Taiwan, 10002
United Kingdom
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Novartis Investigative Site
Portsmouth, United Kingdom, PO6 6AD
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Layout table for investigator information
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] November 27, 2018
Statistical Analysis Plan  [PDF] September 29, 2020

Additional Information:
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03948334    
Other Study ID Numbers: CZPL389A2203E1
2018-000595-15 ( EudraCT Number )
First Posted: May 13, 2019    Key Record Dates
Results First Posted: July 20, 2021
Last Update Posted: October 8, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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


Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
atopic dermatitis
AD
eczema
itch
pruritus
H4R
ZPL389
Additional relevant MeSH terms:
Layout table for MeSH terms
Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases