Atopic DermatitisPhase 2ZESTExtNCT03948334
A Study to Assess the Safety and Efficacy of ZPL389 With TCS/TCI in Atopic Dermatitis Patients
A Phase 2 study testing ZPL389 30mg, ZPL389 50mg and TCS and/or TCI in people with Atopic Dermatitis, run by Novartis Pharmaceuticals at 48 sites in 13 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atopic Dermatitis
- What is being tested?
- ZPL389 30mg, ZPL389 50mg and TCS and/or TCI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 48 sitesin 13 countries
- Study dates
- 4 Apr 2019to 25 Aug 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
48 sites in 13 countries.
48 sites in 13 countries
Japan11 sites
Novartis Investigative Site
Fukuoka, 819 0167
Novartis Investigative Site
Fukuoka, 819-0373
Novartis Investigative Site
Kyoto, 606 8507
Novartis Investigative Site
Nagoya, Aichi-ken, 467-8602
Novartis Investigative Site
Sakai, Osaka, 593-8324
Novartis Investigative Site
Sapporo, Hokkaido, 060-0063
Novartis Investigative Site
Shinjuku Ku, Tokyo, 162 8655
Novartis Investigative Site
Shinjuku-ku, Tokyo, 160-0023
Novartis Investigative Site
Tokyo, 158 0097
Novartis Investigative Site
Yokohama, Kanagawa, 220-6208
Novartis Investigative Site
Yokohama, Kanagawa, 221-0825
Germany10 sites
Novartis Investigative Site
Bielefeld, 33647
Novartis Investigative Site
Gera, 07548
Novartis Investigative Site
Hamburg, 20537
Novartis Investigative Site
Hamburg, 22391
Novartis Investigative Site
Hanover, 30625
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Memmingen, 87700
Novartis Investigative Site
München, 80337
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Osnabrück, 49074
Russia7 sites
Novartis Investigative Site
Chelyabinsk, 454092
Novartis Investigative Site
Kazan', 420012
Novartis Investigative Site
Moscow, 123182
Novartis Investigative Site
Saint Petersburg, 191123
Novartis Investigative Site
Saint Petersburg, 194354
Novartis Investigative Site
Saint Petersburg, 196143
Novartis Investigative Site
Smolensk, 214019
Slovakia4 sites
Novartis Investigative Site
Bardejov, SVK, 085 01
Novartis Investigative Site
Bratislava, 85101
Novartis Investigative Site
Levice, 934 01
Novartis Investigative Site
Svidník, 08901
Poland3 sites
Novartis Investigative Site
Rzeszów, 35 055
Novartis Investigative Site
Warsaw, Mazowian, 02 495
Novartis Investigative Site
Warsaw, 04141
United States2 sites
Novartis Investigative Site
Fairborn, Ohio, 45324
Novartis Investigative Site
Litchfield Park, Arizona, 85340
Finland2 sites
Novartis Investigative Site
Helsinki, 00250
Novartis Investigative Site
Turku, 20520
Netherlands2 sites
Novartis Investigative Site
Bergen op Zoom, 4624 VT
Novartis Investigative Site
Breda, CK, 4818
Taiwan2 sites
Novartis Investigative Site
Taichung, Taiwan ROC, 40201
Novartis Investigative Site
Taipei, 10002
United Kingdom2 sites
Novartis Investigative Site
London, SE1 9RT
Novartis Investigative Site
Portsmouth, PO6 6AD
About this study
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.
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).
Read the 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.
- Conditions
- Atopic Dermatitis
- Being tested
- ZPL389 30mg, ZPL389 50mg, TCS and/or TCI
- Keywords
- atopic dermatitis, AD, eczema, itch, pruritus, H4R, ZPL389
- Medical subject headings
- Dermatitis, Atopic, Eczema, Pruritus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZPL389 30mgDrug
30mg of ZPL389; once daily
ZPL389 50mgDrug
50mg of ZPL389; once daily
TCS and/or TCIDrug
Topical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity.
| Study group | Role | What they receive |
|---|---|---|
| ZPL389 30mg | Experimental | 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 Receives: Drug: ZPL389 30mg; Drug: TCS and/or TCI |
| ZPL389 50mg | Experimental | 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 Receives: Drug: ZPL389 50mg; Drug: TCS and/or TCI |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks (week 16 to week 32 referring to core study)
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.
Measured: From week 16 to week 67 of this extension study (week 32 to week 83 referring to core study)
Secondary outcomes (3)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start4 Apr 2019
- Primary completion23 Jul 2020
- Study completion25 Aug 2020
Why it stopped: Core terminated due to lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Atopic DermatitisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03948334
- Sponsor's protocol ID
- CZPL389A2203E1
- Other IDs
- 2018-000595-15, 2018
- Acronym
- ZESTExt
- Status last verified
- Oct 2021
- First submitted
- 4 Apr 2019
- Last updated
- 8 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03948334
- Acronym / sponsor ID
- ZESTExt / CZPL389A2203E1
- Conditions
- Atopic Dermatitis
- Keywords
- atopic dermatitis, AD, eczema, itch, pruritus, H4R, ZPL389
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Core terminated due to lack of efficacy
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 4 Apr 2019 (actual)
- Primary completion
- 23 Jul 2020 (actual)
- Study completion
- 25 Aug 2020 (actual)
- First posted
- 13 May 2019 (actual)
- Results
- Posted 20 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ZPL389 30mg | Experimental | Drug: ZPL389 30mg, Drug: TCS and/or TCI30mg 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 |
| ZPL389 50mg | Experimental | Drug: ZPL389 50mg, Drug: TCS and/or TCI50mg 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZPL389 30mg30mg of ZPL389; once daily | Drug | ZPL389 30mg |
| ZPL389 50mg50mg of ZPL389; once daily | Drug | ZPL389 50mg |
| TCS and/or TCITopical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity. | Drug | ZPL389 30mg, ZPL389 50mg |
Primary outcome
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.
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.
3 secondary outcomes
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)
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
48 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZPL389 30mg, ZPL389 50mg and TCS and/or TCI in people with Atopic Dermatitis, run by Novartis Pharmaceuticals at 48 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 sites in Japan, Germany, Russia, Slovakia, Poland and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.