A Phase 2 interventional study of ZPL389 30mg and ZPL389 50mg in Atopic Dermatitis, sponsored by Novartis Pharmaceuticals. Terminated at 48 sites in 13 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-08.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
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).
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.
1,419 studies on the registry are indexed under Dermatitis, Atopic; 258 are open to participants now.
This study's enrollment of 123 is above the median of 83 across 1,125 interventional studies indexed under Dermatitis, Atopic.
Browse Dermatitis, Atopic studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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 · Drug: TCS and/or TCI
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 · Drug: TCS and/or TCI
30mg of ZPL389; once daily
50mg of ZPL389; once daily
Topical corticosteroids (TCS) and /or topical calcineurin inhibitors (TCI) were used concomitantly or intermittently based on disease severity.
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.
Time frame: 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.
Time frame: From week 16 to week 67 of this extension study (week 32 to week 83 referring to core study)
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.
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
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)
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.
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)
| Milestone | ZPL389 30mg | ZPL389 50mg |
|---|---|---|
| Started | 60 | 63 |
| Completed | 0 | 0 |
| Not completed | 60 | 63 |
| Withdrew: Adverse event | 1 | 4 |
| Withdrew: Lack of efficacy | 2 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 |
| Withdrew: Pregnancy | 0 | 1 |
| Withdrew: Protocol deviation | 1 | 0 |
| Withdrew: Study terminated by sponsor | 50 | 51 |
| Withdrew: Subject decision /guardian decision | 4 | 7 |
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.
| Participants | ZPL389 30mg | ZPL389 50mg |
|---|---|---|
| Adverse events | 29 | 33 |
| SAEs | 2 | 5 |
| AEs leading to discontinuation | 2 | 3 |
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.
| Participants | ZPL389 30mg | ZPL389 50mg |
|---|---|---|
| Adverse events | 18 | 20 |
| SAEs | 0 | 2 |
| AEs leading to discontinuation | 0 | 1 |
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 participants | ZPL389 30mg Re-randomized After Core Study | ZPL389 50mg Re-randomized After Core Study | ZPL389 30mg Continuing After Core Study | ZPL389 50mg Continuing After Core Study |
|---|---|---|---|---|
| week 4 (week 20 referring to core study) | 2.9 (-2.7 to 8.6) | 5.2 (-3.4 to 13.8) | 0.0 (-0.0 to 0.0) | 3.0 (-2.8 to 8.9) |
| Week 8 (week 24 referring to core study) | 2.9 (-2.7 to 8.6) | 4.8 (-3.9 to 13.5) | 0.0 (-0.0 to 0.0) | 3.1 (-2.8 to 9.0) |
| Week 12 (week 28 referring to core study) | 3.5 (-3.1 to 10.1) | 4.0 (-4.4 to 12.4) | 0.0 (-1.0 to 1.1) | 3.0 (-2.8 to 8.9) |
| Week 16 (week 32 referring to core study) | 3.9 (-3.3 to 11.0) | 5.9 (-3.7 to 15.5) | 0.0 (-1.7 to 1.9) | 0.0 (-2.0 to 2.4) |
| Week 28 (week 44 referring to core study) | 0.0 (-3.7 to 6.4) | 7.5 (-3.7 to 18.7) | 0.0 (-1.4 to 1.6) | 1.5 (-3.8 to 6.9) |
| Week 40 (week 56 referring to core study) | 3.4 (-4.4 to 11.2) | 9.1 (-2.7 to 20.8) | 0.0 (-4.3 to 7.0) | 0.0 (-4.2 to 7.0) |
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 participants | ZPL389 30mg Re-randomized After Core Study | ZPL389 50mg Re-randomized After Core Study | ZPL389 30mg Continuing After Core Study | ZPL389 50mg Continuing After Core Study |
|---|---|---|---|---|
| week 4 (week 20 referring to core study) | 14.7 (2.8 to 26.6) | 13.0 (0.8 to 25.2) | 7.7 (-2.6 to 17.9) | 12.1 (1.0 to 23.3) |
| Week 8 (week 24 referring to core study) | 17.6 (4.8 to 30.5) | 15.6 (2.2 to 29.0) | 11.5 (-0.7 to 23.8) | 12.1 (1.0 to 23.3) |
| Week 12 (week 28 referring to core study) | 22.3 (8.0 to 36.6) | 15.9 (2.5 to 29.3) | 10.7 (-1.5 to 23.0) | 12.1 (1.0 to 23.3) |
| Week 16 (week 32 referring to core study) | 19.6 (5.7 to 33.4) | 18.2 (3.8 to 32.6) | 10.1 (-2.0 to 22.2) | 11.9 (0.5 to 23.3) |
| Week 28 (week 44 referring to core study) | 10.8 (-1.0 to 22.6) | 14.8 (0.8 to 28.8) | 14.0 (0.1 to 27.8) | 14.2 (1.6 to 26.8) |
| Week 40 (week 56 referring to core study) | 14.8 (1.4 to 28.2) | 20.3 (4.6 to 36.1) | 12.3 (-0.9 to 25.5) | 13.8 (0.9 to 26.6) |
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.
| Percentage of participants | ZPL389 30mg Re-randomized After Core Study | ZPL389 50mg Re-randomized After Core Study | ZPL389 30mg Continuing After Core Study | ZPL389 50mg Continuing After Core Study |
|---|---|---|---|---|
| week 4 (week 20 referring to core study) | 5.9 (-2.0 to 13.8) | 8.8 (-1.8 to 19.4) | 0.0 (-0.0 to 0.0) | 12.1 (1.0 to 23.3) |
| Week 8 (week 24 referring to core study) | 5.9 (-2.0 to 13.8) | 14.2 (1.0 to 27.4) | 0.0 (-0.0 to 0.0) | 9.1 (-0.7 to 18.9) |
| Week 12 (week 28 referring to core study) | 12.0 (1.0 to 23.1) | 11.4 (-0.6 to 23.4) | 4.6 (-4.0 to 13.2) | 12.1 (1.0 to 23.3) |
| Week 16 (week 32 referring to core study) | 8.4 (-1.8 to 18.7) | 10.3 (-1.3 to 22.0) | 0.0 (-4.2 to 6.6) | 4.9 (-3.0 to 12.8) |
| Week 28 (week 44 referring to core study) | 8.2 (-2.0 to 18.5) | 8.9 (-2.9 to 20.8) | 0.0 (-4.0 to 5.9) | 2.6 (-4.6 to 9.9) |
| Week 40 (week 56 referring to core study) | 10.0 (-2.4 to 22.3) | 13.5 (-0.2 to 27.3) | 6.1 (-4.0 to 16.2) | 3.2 (-4.4 to 10.8) |
Collected over Adverse events were collected from first dose of study treatment in this extension study until end of study treatment plus 4 weeks post treatment, up to maximum duration of 67 weeks (week 16 to week 83 referring to core study).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| ZPL389 30mg in the First 16 Weeks of This Extension Study | 0/60 (0%) | 2/60 (3.3%) | 6/60 (10%) |
| ZPL389 50mg in the First 16 Weeks of This Extension Study | 0/63 (0%) | 5/63 (7.9%) | 8/63 (12.7%) |
| ZPL389 30 mg After 16 Weeks of Treatment in This Extension Study | 0/60 (0%) | 0/60 (0%) | 9/60 (15%) |
| ZPL389 50 mg After 16 Weeks of Treatment in This Extension Study | 0/63 (0%) | 2/63 (3.2%) | 6/63 (9.5%) |
| Event | ZPL389 30mg in the First 16 Weeks of This Extension Study | ZPL389 50mg in the First 16 Weeks of This Extension Study | ZPL389 30 mg After 16 Weeks of Treatment in This Extension Study | ZPL389 50 mg After 16 Weeks of Treatment in This Extension Study |
|---|---|---|---|---|
| ProstatitisReproductive system and breast disorders | 1/60 | 0/63 | 0/60 | 0/63 |
| AsthmaRespiratory, thoracic and mediastinal disorders | 1/60 | 0/63 | 0/60 | 0/63 |
| Abdominal painGastrointestinal disorders | 0/60 | 1/63 | 0/60 | 0/63 |
| SteatohepatitisHepatobiliary disorders | 0/60 | 0/63 | 0/60 | 1/63 |
| BronchiolitisInfections and infestations | 0/60 | 1/63 | 0/60 | 0/63 |
| BronchitisInfections and infestations | 0/60 | 1/63 | 0/60 | 0/63 |
| Ankle fractureInjury, poisoning and procedural complications | 0/60 | 0/63 | 0/60 | 1/63 |
| Ovarian cystReproductive system and breast disorders | 0/60 | 1/63 | 0/60 | 0/63 |
| Pneumothorax spontaneousRespiratory, thoracic and mediastinal disorders | 0/60 | 1/63 | 0/60 | 0/63 |
| Dermatitis atopicSkin and subcutaneous tissue disorders | 0/60 | 1/63 | 0/60 | 0/63 |
| Event | ZPL389 30mg in the First 16 Weeks of This Extension Study | ZPL389 50mg in the First 16 Weeks of This Extension Study | ZPL389 30 mg After 16 Weeks of Treatment in This Extension Study | ZPL389 50 mg After 16 Weeks of Treatment in This Extension Study |
|---|---|---|---|---|
| NasopharyngitisInfections and infestations | 6/60 | 4/63 | 8/60 | 3/63 |
| Dermatitis atopicSkin and subcutaneous tissue disorders | 1/60 | 4/63 | 1/60 | 3/63 |
| Age, Continuous(years) | ZPL389 30mg | ZPL389 50mg | Total |
|---|---|---|---|
| Mean | 34.8 ± 12.18 | 34.4 ± 11.24 | 34.6 ± 11.66 |
| Sex: Female, Male(Participants) | ZPL389 30mg | ZPL389 50mg | Total |
|---|---|---|---|
| Female | 24 | 20 | 44 |
| Male | 36 | 43 | 79 |
| Race/Ethnicity, Customized(Participants) | ZPL389 30mg | ZPL389 50mg | Total |
|---|---|---|---|
| White | 36 | 42 | 78 |
| Black or African American | 1 | 1 | 2 |
| Asian | 23 | 20 | 43 |
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Plan to share: 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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