Clinical trial NCT02795832: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Ziarco Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2016-06-10
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Percent Change From Baseline in EASI Score in Cohort 3
timeFrame: Day 1 and Day 14
measure: Percent Change From Baseline in EASI Score Over Time in Cohort 3 - Observed Case
timeFrame: Days 1, 5, 8, 10, and 15
Secondary outcomes:
measure: Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3
timeFrame: Day 14
measure: Percentage of Responders on Investigators Global Assessment in Cohort 3
timeFrame: Day 14
measure: Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3
timeFrame: Day 1 to day 14
measure: Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3
timeFrame: End of treatment (day 15)
measure: Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3
timeFrame: Day 1 to day 14
Other outcomes:
measure: ZPL-5212372 Cmax for Patients in Cohort 2
timeFrame: Day 1, Day 7
measure: ZPL-5212372 AUCt for Patients in Cohort 2
timeFrame: Day 1, Day 7
measure: ZPL-5212372 Trough Plasma Concentrations in Cohort 3
timeFrame: Day 5, Day 8, Day 10, Day 15
Locations:
city: Blackpool
country: United Kingdom
facility: MAC
city: Leeds
country: United Kingdom
facility: MAC
city: Manchester
country: United Kingdom
facility: MAC
Study officials:
affiliation: Novartis
name: Anne Parneix, MD
role: STUDY_DIRECTOR
References: