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

Phase 2

Terminated

• Conditions: Atopic Dermatitis
• Interventions: Drug: ZPL389 50mg; Drug: ZPL389 10mg; Drug: Placebo; Drug: ZPL389 3mg; Drug: ZPL389 30mg

• Registration Number: NCT03517566
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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

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 Timeline

• Study First Submitted: 2018-03-27
• Study First Submitted QC: 2018-04-24
• Study First Posted: 2018-05-07
• Study Start: 2018-11-14
• Primary Completion: 2020-07-15
• Study Completion: 2020-08-06
• Results First Submitted: 2021-04-07
• Results First Submitted QC: 2021-06-29
• Results First Posted: 2021-07-20
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-07
• Last Update Posted: 2021-10-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 293

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ZPL389 50mg	ZPL389 50mg	ZPL389 50 mg oral powder
ZPL389 10 mg	ZPL389 10mg	ZPL389 10 mg oral powder
placebo	Placebo	Placebo
ZPL389 3mg	ZPL389 3mg	ZPL389 3 mg oral powder
ZPL389 30mg	ZPL389 30mg	ZPL389 30 mg oral powder

Primary Outcome Measures

Name	Time	Method
Percentage of IGA Responders at Week 16	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.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in EASI Score at Week 16	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.
Percent Change From Baseline in EASI Score Over Time	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.
Percentage of EASI50 Responders Over Time	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
Percentage of EASI75 Responders Over Time	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
Percentage of IGA Responders Over Time	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.
Number of Patients With Adverse Events	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.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 Portsmouth, United Kingdom