Back to resultsA Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis
Primary Purpose
Atopic Dermatitis
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
ZPL-5212372 1% w/w Ointment BID
Placebo Ointment BID
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis
Eligibility Criteria
Inclusion Criteria:
- Healthy males or females, aged between 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).
or
Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 6 months prior to screening. AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka.
For Atopic Dermatitis Patients:
Eczema Area and Severity Index (EASI) of ≥9 and <48 at Screening and an EASI of ≥12 and <48 at Day 1.
An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 1.
Atopic dermatitis affecting between ≥10 to <40% BSA at Screening and ≥10% to <50% BSA on Day 1.
All Subjects:
Evidence of a personally signed and dated informed consent form, indicating that the subject has been informed of all pertinent aspects of the study.
Exclusion Criteria:
For Healthy Subjects
- Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
- Have tattoos covering areas of skin to be dosed with study ointment.
- Subjects who are hirsute in areas of skin to be dosed with study ointment.
- Subjects who have received treatment with an investigational drug within 3 months prior to screening.
For Atopic Dermatitis Patients:
- AD of such severity (EASI >48) that the subject could not comply with the demands of the study and/or the subject is not a suitable candidate for a placebo-controlled study.
- Have concomitant skin disease or infection (e.g. acne, impetigo) or presence of skin comorbidities in the study area to be dosed that may interfere with study assessments.
- Have received phototherapy (e.g. UVA, UVB or PUVA therapy), or systemic therapy (e.g. immunosuppressants [such as cyclosporine, azathioprine, methotrexate], cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the study. All other biologics should not have been used within 3 months of the start of study.
- Have received systemic corticosteroids (e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the study. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate.
- Patients treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting study; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.
Sites / Locations
- MAC
- MAC
- MAC
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Cohort 1a
Cohort 1b
Cohort 2a
Cohort 2b
Cohort 3a
Cohort 3b
Arm Description
ZPL-5212372 1% w/w Ointment BID
Placebo Ointment BID
ZPL-5212372 1% w/w Ointment BID
Placebo Ointment BID
ZPL-5212372 1% w/w OIntment BID
Placebo Ointment BID
Outcomes
Primary Outcome Measures
Percent Change From Baseline in EASI Score in Cohort 3
The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease.
Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case
The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease.
Secondary Outcome Measures
Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3
The proportion of subjects who achieved EASI-50 and EASI-75 responses at Week 2 were compared between treatment groups.
EASI-50 was defined as a ≥50% reduction from baseline in EASI score at Week 2. EASI-75 was defined as a ≥75% reduction from baseline in EASI score at Week 2.
Percentage of Responders on Investigators Global Assessment in Cohort 3
The following secondary endpoints were assessed for IGA:
A subject was considered as having IGA success if they achieved a score of 'Clear' or 'Almost clear'; note, as subjects required a score of ≥3 to enter the study they must have had a reduction of ≥2 from baseline to achieve success A subject was considered as having an IGA response if they achieved a score of 'Clear' or 'Almost clear', or a reduction of ≥2 from baseline IGA was summarized for the FAS with counts and percentages by treatment at each visit.
Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3
Numerical Rating Scale (NRS) for Pruritus (worst itch). The Pruritus NRS is an assessment tool that will be used to assess the subject's worst itch as a result of AD in the previous 24 hours.
They will be asked the following question:
On a scale of 0 (No Itching) to 10 (Itching as bad as you can imagine), please rate the WORST itching that you felt over the last 24 hours.
Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3
Patient Global Impression of Change (PGIC) The PGIC scores were summarised for the FAS with counts and percentages in each treatment group. All data collected were included.
The PGIC was dichotomized into responders, defined as responses of 'Very Much Improved', 'Much Improved' or 'Minimally improved' and non-responders (all other responses plus missing data).
Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3
Body Surface Area (BSA). The percentage BSA affected was summarised at each visit, including change from baseline, by treatment group, using the Full Analysis Set.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02795832
Brief Title
A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis
Official Title
A Randomised, Double-blind, Placebo Controlled Study to Determine the Safety, Pharmacokinetics and Efficacy of Topical ZPL-5212372 Ointment Administered BID for up to 2 Weeks in Healthy Subjects and Subjects With Atopic Dermatitis.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
June 2016 (undefined)
Primary Completion Date
March 1, 2017 (Actual)
Study Completion Date
March 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ziarco Pharma Ltd
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
A Randomised, Adaptive Design, Double-Blind (3rd Party Open), Placebo Controlled, Sequential Group Study to Determine the Safety,Tolerability, Pharmacokinetics and Efficacy of Twice Daily Application of a Topical ZPL-5212372 (1.0% w/w) Ointment Administered for up to 2 Weeks in Adult Healthy Volunteers and Patients with Moderate to Severe Atopic Dermatitis
Detailed Description
This study was a randomised, adaptive design, double blind (3rd party open), placebo controlled, sequential group study in both healthy volunteers and patients with moderate to severe AD. This study was divided into 3 separate, sequential cohorts:
Cohort 1 were to assess safety, toleration and pharmacokinetics (PK) with intensive monitoring as in-patients over 7 days of dosing in healthy volunteers.
Cohort 2 were to assess safety, toleration and PK with intensive monitoring as in-patients over 7 days of dosing in moderate to severe AD patients.
Cohort 3 were to assess efficacy, safety, toleration and PK as out-patients over 14 days of dosing in moderate to severe AD patients.
Subjects received 1.0% (w/w) ZPL-5212372 or matched placebo ointment topically, twice daily.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1a
Arm Type
Experimental
Arm Description
ZPL-5212372 1% w/w Ointment BID
Arm Title
Cohort 1b
Arm Type
Placebo Comparator
Arm Description
Placebo Ointment BID
Arm Title
Cohort 2a
Arm Type
Experimental
Arm Description
ZPL-5212372 1% w/w Ointment BID
Arm Title
Cohort 2b
Arm Type
Placebo Comparator
Arm Description
Placebo Ointment BID
Arm Title
Cohort 3a
Arm Type
Experimental
Arm Description
ZPL-5212372 1% w/w OIntment BID
Arm Title
Cohort 3b
Arm Type
Placebo Comparator
Arm Description
Placebo Ointment BID
Intervention Type
Drug
Intervention Name(s)
ZPL-5212372 1% w/w Ointment BID
Intervention Type
Drug
Intervention Name(s)
Placebo Ointment BID
Primary Outcome Measure Information:
Title
Percent Change From Baseline in EASI Score in Cohort 3
Description
The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease.
Time Frame
Day 1 and Day 14
Title
Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case
Description
The EASI is a validated tool used to measure the severity and extent of atopic eczema (Eczema Area and Severity Index). The body is divided into 4 sections of total skin area: head including neck (10%); arms including extremities (20%); trunk (30%) and legs including extremities (40%). Each area is scored and the 4 scores are combined into the final EASI. The severity parameters are measured on a scale of 0 to 3 (from none to severe). For each section, the percentage area of skin involved with eczema is estimated and transformed into an extent grade from 0 to 6, from 0% of involved skin area with eczema to 90-100% of involved skin area with eczema. The sum of all four severity parameters is calculated for each section of skin and then multiplied by the weight of the respective section. This value is then multiplied by the extent score for that body area. The EASI value can range from 0-72, a higher score indicates more severe disease.
Time Frame
Days 1, 5, 8, 10, and 15
Secondary Outcome Measure Information:
Title
Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3
Description
The proportion of subjects who achieved EASI-50 and EASI-75 responses at Week 2 were compared between treatment groups.
EASI-50 was defined as a ≥50% reduction from baseline in EASI score at Week 2. EASI-75 was defined as a ≥75% reduction from baseline in EASI score at Week 2.
Time Frame
Day 14
Title
Percentage of Responders on Investigators Global Assessment in Cohort 3
Description
The following secondary endpoints were assessed for IGA:
A subject was considered as having IGA success if they achieved a score of 'Clear' or 'Almost clear'; note, as subjects required a score of ≥3 to enter the study they must have had a reduction of ≥2 from baseline to achieve success A subject was considered as having an IGA response if they achieved a score of 'Clear' or 'Almost clear', or a reduction of ≥2 from baseline IGA was summarized for the FAS with counts and percentages by treatment at each visit.
Time Frame
Day 14
Title
Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3
Description
Numerical Rating Scale (NRS) for Pruritus (worst itch). The Pruritus NRS is an assessment tool that will be used to assess the subject's worst itch as a result of AD in the previous 24 hours.
They will be asked the following question:
On a scale of 0 (No Itching) to 10 (Itching as bad as you can imagine), please rate the WORST itching that you felt over the last 24 hours.
Time Frame
Day 1 to day 14
Title
Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3
Description
Patient Global Impression of Change (PGIC) The PGIC scores were summarised for the FAS with counts and percentages in each treatment group. All data collected were included.
The PGIC was dichotomized into responders, defined as responses of 'Very Much Improved', 'Much Improved' or 'Minimally improved' and non-responders (all other responses plus missing data).
Time Frame
End of treatment (day 15)
Title
Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3
Description
Body Surface Area (BSA). The percentage BSA affected was summarised at each visit, including change from baseline, by treatment group, using the Full Analysis Set.
Time Frame
Day 1 to day 14
Other Pre-specified Outcome Measures:
Title
ZPL-5212372 Cmax for Patients in Cohort 2
Description
PK parameters for patients who had ointment applied over 40% BSA.
Time Frame
Day 1, Day 7
Title
ZPL-5212372 AUCt for Patients in Cohort 2
Description
PK parameters for patients who had ointment applied over 40% BSA.
Time Frame
Day 1, Day 7
Title
ZPL-5212372 Trough Plasma Concentrations in Cohort 3
Description
PK parameters for patients who had ointment applied over 40% BSA.
Time Frame
Day 5, Day 8, Day 10, Day 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Healthy males or females, aged between 18 and 55 years, inclusive (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests).
or
Males and females aged 18-65 years inclusive with physician documented history or diagnosis of atopic dermatitis for at least 6 months prior to screening. AD should be diagnosed by the Eichenfield revised criteria of Hanifin and Rajka.
For Atopic Dermatitis Patients:
Eczema Area and Severity Index (EASI) of ≥9 and <48 at Screening and an EASI of ≥12 and <48 at Day 1.
An Investigator's Global Assessment (IGA) score ≥ 3 at both Screening and Day 1.
Atopic dermatitis affecting between ≥10 to <40% BSA at Screening and ≥10% to <50% BSA on Day 1.
All Subjects:
Evidence of a personally signed and dated informed consent form, indicating that the subject has been informed of all pertinent aspects of the study.
Exclusion Criteria:
For Healthy Subjects
Evidence or history of clinically significant haematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
Have tattoos covering areas of skin to be dosed with study ointment.
Subjects who are hirsute in areas of skin to be dosed with study ointment.
Subjects who have received treatment with an investigational drug within 3 months prior to screening.
For Atopic Dermatitis Patients:
AD of such severity (EASI >48) that the subject could not comply with the demands of the study and/or the subject is not a suitable candidate for a placebo-controlled study.
Have concomitant skin disease or infection (e.g. acne, impetigo) or presence of skin comorbidities in the study area to be dosed that may interfere with study assessments.
Have received phototherapy (e.g. UVA, UVB or PUVA therapy), or systemic therapy (e.g. immunosuppressants [such as cyclosporine, azathioprine, methotrexate], cytostatics) known or suspected to have an effect on AD, within 4 weeks of the start of the study. All other biologics should not have been used within 3 months of the start of study.
Have received systemic corticosteroids (e.g. oral, intravenous, intraarticular, rectal) within 4 weeks of the start of the study. Subjects on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal CS may participate.
Patients treated with oral antihistamines or topical calcineurin inhibitors or topical steroids within 7 days of starting study; intranasal antihistamines for the treatment of allergic rhinitis are acceptable.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Parneix, MD
Organizational Affiliation
Novartis
Official's Role
Study Director
Facility Information:
Facility Name
MAC
City
Blackpool
Country
United Kingdom
Facility Name
MAC
City
Leeds
Country
United Kingdom
Facility Name
MAC
City
Manchester
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis
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