A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis

NCT02795832 | Completed Phase 1 Results

• 1 other identifier: Ziarcopharma
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 3

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

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (2)

• 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.

  Day 1 and Day 14

• 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.

  Days 1, 5, 8, 10, and 15

Secondary Outcomes (5)

• Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3

  Day 14

• Percentage of Responders on Investigators Global Assessment in Cohort 3

  Day 14

• Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3

  Day 1 to day 14

• Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3

  End of treatment (day 15)

• Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3

  Day 1 to day 14

Other Outcomes (3)

• ZPL-5212372 Cmax for Patients in Cohort 2

  Day 1, Day 7

• ZPL-5212372 AUCt for Patients in Cohort 2

  Day 1, Day 7

• ZPL-5212372 Trough Plasma Concentrations in Cohort 3

  Day 5, Day 8, Day 10, Day 15

Study Arms (6)

Cohort 1a

EXPERIMENTAL

ZPL-5212372 1% w/w Ointment BID

Drug: ZPL-5212372 1% w/w Ointment BID

Cohort 1b

PLACEBO COMPARATOR

Placebo Ointment BID

Drug: Placebo Ointment BID

Cohort 2a

EXPERIMENTAL

ZPL-5212372 1% w/w Ointment BID

Drug: ZPL-5212372 1% w/w Ointment BID

Cohort 2b

PLACEBO COMPARATOR

Placebo Ointment BID

Drug: Placebo Ointment BID

Cohort 3a

EXPERIMENTAL

ZPL-5212372 1% w/w OIntment BID

Drug: ZPL-5212372 1% w/w Ointment BID

Cohort 3b

PLACEBO COMPARATOR

Placebo Ointment BID

Drug: Placebo Ointment BID

Interventions

ZPL-5212372 1% w/w Ointment BID DRUG

Cohort 1a; Cohort 2a; Cohort 3a

Placebo Ointment BID DRUG

Cohort 1b; Cohort 2b; Cohort 3b

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ziarco Pharma Ltd: lead

Study Sites (3)

MAC

Blackpool, United Kingdom

Location

MAC

Leeds, United Kingdom

Location

MAC

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Dermatitis, Atopic

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Anne Parneix, MD

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2016
• First Posted: June 10, 2016
• Study Start: June 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 5, 2019
• Results First Posted: April 5, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)