Atopic DermatitisPhase 1/2NCT02795832
A Study to Determine the Safety & Efficacy of ZPL-5212372 in Healthy Subjects and in Subjects With Atopic Dermatitis
A Phase 1/2 study testing ZPL-5212372 1% w/w Ointment BID in people with Atopic Dermatitis, run by Ziarco Pharma Ltd at 3 sites in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Atopic Dermatitis
- What is being tested?
- ZPL-5212372 1% w/w Ointment BID
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Jun 2016to 1 Mar 2017
- Phase
- Phase 1/2
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
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- 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.
Trial locations and contacts
3 sites in 1 country.
About this study
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.
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
Read the 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.
- Conditions
- Atopic Dermatitis
- Being tested
- ZPL-5212372 1% w/w Ointment BID, Placebo Ointment BID
- Medical subject headings
- Dermatitis, Atopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZPL-5212372 1% w/w Ointment BIDDrug
Placebo Ointment BIDDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1a | Experimental | ZPL-5212372 1% w/w Ointment BID Receives: Drug: ZPL-5212372 1% w/w Ointment BID |
| Cohort 1b | Placebo comparator | Placebo Ointment BID Receives: Drug: Placebo Ointment BID |
| Cohort 2a | Experimental | ZPL-5212372 1% w/w Ointment BID Receives: Drug: ZPL-5212372 1% w/w Ointment BID |
| Cohort 2b | Placebo comparator | Placebo Ointment BID Receives: Drug: Placebo Ointment BID |
| Cohort 3a | Experimental | ZPL-5212372 1% w/w OIntment BID Receives: Drug: ZPL-5212372 1% w/w Ointment BID |
| Cohort 3b | Placebo comparator | Placebo Ointment BID Receives: Drug: Placebo Ointment BID |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Days 1, 5, 8, 10, and 15
Secondary outcomes (5)
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.
Measured: Day 14
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.
Measured: Day 14
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.
Measured: Day 1 to day 14
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).
Measured: End of treatment (day 15)
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.
Measured: Day 1 to day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2016 (estimated)
- Study startJun 2016
- Primary completion1 Mar 2017
- Study completion1 Mar 2017
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ziarco Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anne Parneix, MD, Study director, Novartis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02795832
- Sponsor's protocol ID
- Ziarcopharma
- Status last verified
- Apr 2019
- First submitted
- 6 Jun 2016
- Last updated
- 5 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02795832
- Acronym / sponsor ID
- Ziarcopharma
- Conditions
- Atopic Dermatitis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Ziarco Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- Jun 2016
- Primary completion
- 1 Mar 2017 (actual)
- Study completion
- 1 Mar 2017 (actual)
- First posted
- 10 Jun 2016 (estimated)
- Results
- Posted 5 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort 1a | Experimental | Drug: ZPL-5212372 1% w/w Ointment BIDZPL-5212372 1% w/w Ointment BID |
| Cohort 1b | Placebo comparator | Drug: Placebo Ointment BIDPlacebo Ointment BID |
| Cohort 2a | Experimental | Drug: ZPL-5212372 1% w/w Ointment BIDZPL-5212372 1% w/w Ointment BID |
| Cohort 2b | Placebo comparator | Drug: Placebo Ointment BIDPlacebo Ointment BID |
| Cohort 3a | Experimental | Drug: ZPL-5212372 1% w/w Ointment BIDZPL-5212372 1% w/w OIntment BID |
| Cohort 3b | Placebo comparator | Drug: Placebo Ointment BIDPlacebo Ointment BID |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- 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.
Key exclusion criteria (11 listed)
- 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.
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 |
|---|---|---|
| ZPL-5212372 1% w/w Ointment BID | Drug | Cohort 1a, Cohort 2a, Cohort 3a |
| Placebo Ointment BID | Drug | Cohort 1b, Cohort 2b, Cohort 3b |
Primary outcome
Percent Change From Baseline in EASI Score in Cohort 3
Time frame: Day 1 and Day 14
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
Time frame: Days 1, 5, 8, 10, and 15
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.
5 secondary outcomes
Summary of EASI-50 and EASI-75 Responders at Week 2 - Cohort 3
Time frame: Day 14
Percentage of Responders on Investigators Global Assessment in Cohort 3
Time frame: Day 14
Change From Baseline in NRS for Pruritus at Week 2 - Observed Case in Cohort 3
Time frame: Day 1 to day 14
Summary of Patient Global Impression of Change and Logistic Regression of Patient Global Impression of Change in Cohort 3
Time frame: End of treatment (day 15)
Change From Baseline in Body Surface Area at Week 2 - Observed Case in Cohort 3
Time frame: Day 1 to day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Anne Parneix, MD study director
Novartis
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ZPL-5212372 1% w/w Ointment BID in people with Atopic Dermatitis, run by Ziarco Pharma Ltd at 3 sites in United Kingdom.
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 9 inclusion and 11 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: finished, as of the sponsor's last update on 5 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 5 Apr 2019). 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?
Percent Change From Baseline in EASI Score in Cohort 3 (time frame: Day 1 and Day 14). 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 5 Apr 2019.