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

Atopic Dermatitis Clinical Trial

— 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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03948334
• Other study ID #: CZPL389A2203E1
• Secondary ID: 2018-000595-15
• Status: Terminated
• Phase: Phase 2
• Start date: April 4, 2019
• Est. completion date: August 25, 2020

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 123
• Est. completion date: August 25, 2020
• Est. primary completion date: July 23, 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
• 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.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema

Intervention

Drug:
• ZPL389 30mg
30mg of ZPL389; once daily
• ZPL389 50mg
50mg of ZPL389; once daily
• TCS and/or TCI
Topical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity.

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Leuven
Canada	Novartis Investigative Site	Toronto	Ontario
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Turku
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Gera
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
Iceland	Novartis Investigative Site	Kopavogur
Japan	Novartis Investigative Site	Fukuoka
Japan	Novartis Investigative Site	Fukuoka
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	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	CK
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	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigative Site	Smolensk
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	London
United Kingdom	Novartis Investigative Site	Portsmouth
United States	Novartis Investigative Site	Fairborn	Ohio
United States	Novartis Investigative Site	Litchfield Park	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	16 weeks (week 16 to week 32 referring to core study)
Primary	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.	From week 16 to week 67 of this extension study (week 32 to week 83 referring to core study)
Secondary	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.	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)
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.; 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.	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)
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 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.	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)

External Links

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