Clinical trial NCT03703895
Conditions: Hand Dermatitis
Sponsor: The Center for Clinical and Cosmetic Research
Start date: 2018-09-18; Completion date: 2019-04-04
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a double-blind, pilot study with 20 subjects to determine the tolerability and efficacy of topical AFX 5931 in the treatment of mild to moderate hand dermatitis. Subjects are screened up to 30 days before the baseline visit. Subjects who meet the eligibility criteria may qualify for the study. Subjects will be randomized in a 3:1 ratio to receive either the active or vehicle medication. 15 subjects will receive the active, therapeutic product and 5 subjects will receive the inactive, vehicle product.

Detailed description:
This is a double-blind, pilot study with 20 subjects to determine the tolerability and efficacy of topical AFX 5931 in the treatment of mild to moderate hand dermatitis. Subjects are screened up to 30 days before the baseline visit. Subjects who meet the eligibility criteria may qualify for the study. Subjects will be randomized in a 3:1 ratio to receive either the active or vehicle medication. 15 subjects will receive the active, therapeutic product and 5 subjects will receive the inactive, vehicle product. Subjects will complete 4 study visits according to the following 4-week timeline: Day \[-30\] - \[-1\] (Screening), Day 0 (Baseline), Day 14 (Follow-Up), Day 28 (Follow-up \| ET \| EOS). At Visit 2, IP will be dispensed and baseline readings of efficacy as well as safety/tolerability assessments will be obtained prior to application of the IP. Subjects will apply IP twice daily and compliance will be monitored by periodically reviewing the subject diary. The evaluations that will be used to measure efficacy of the product will be the Investigator's Global Assessment and Hand Eczema Severity Index. The Subject's Local Dermal Tolerability Assessment and Local Skin Reaction Assessment will be used throughout the course of the study to evaluate tolerability. Additionally, the actions that will be taken to evaluate safety will be the monitoring of adverse events, vital signs, and changes in concomitant medications. Digital photographs will be taken at each visit (excluding Visit 3).

Arms: arm 1: Active Comparator, Topical AFX5931, a medication combining a small, potent anti-inflammatory molecule. Subjects will complete up to 4 study visits where Topical AFX5931 will be applied twice daily for 28 days. arm 2: Placebo Comparator, Topical Placebo. Subjects will complete up to 4 study visits where Topical Placebo will be applied twice daily for 28 days.
Interventions: intervention 1: Topical AFX5931 intervention 2: Topical Placebo
Intervention descriptions: intervention 1: Active Comparator, Topical AFX5931, a medication combining a small, potent anti-inflammatory molecule. intervention 2: Placebo Comparator, Topical Placebo.

Protocol documents:
Prot_SAP_001.pdf: 
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CLINICAL STUDY PROTOCOL
Protocol Title: “A Double-Blind, Pilot Study to Evaluate the Efficacy and Safety of Topical
AFX 5931 in the Treatment of Mild to Moderate Hand Dermatitis”
Protocol Identifier: CCCR 08-2018
Version Date: 09 May 2018
Version: 1.0
Sponsor:
Afecta Pharmaceuticals
STATEMENT OF CONFIDENTIALITY
The information in this document is privileged and confidential. Any distribution, copying, or disclosure
is strictly prohibited unless required by federal regulations or state law. Persons receiving this
information must be notified that it is confidential and may not be further disclosed.


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CLINICAL STUDY PROTOCOL
Protocol Number:
CCCR 08-2018
Protocol Title:
A Double-Blind, Pilot Study to Evaluate the Efficacy and
Safety of Topical AFX 5931 in the Treatment of Mild to
Moderate Hand Dermatitis
Phase:
Pilot – Investigator Initiated Trial (IIT)
Investigational Product:
1.
Topical AFX 5931
Study Sponsor:
Afecta Pharmaceuticals
Principal Investigator:
Mark Steven Nestor, M.D., Ph.D.
Center for Clinical and Cosmetic Research
2925 Aventura Boulevard, Suite 205
Aventura, Florida 33180
Current Version and Date:
Original Protocol – 09 May 2018
The study will be conducted according to the protocol and in compliance with Good Clinical Practice,
USFDA ICH E6, ICH Harmonised Tripartite and all other applicable regulatory requirements.


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SPONSOR SIGNATURE PAGE
This trial is a double-blind, pilot study to evaluate the efficacy and safety of topical AFX 5931 in the
treatment of mild to moderate hand dermatitis.
I agree to conduct this trial in accordance with the requirements of the Clinical Study Protocol and also in
accordance with current versions of the following:
·
Declaration of Helsinki (revised version of Edinburgh, Scotland, 2000, Note of Clarification on
Paragraph 29 added by the World Medical Association General Assembly, Washington 2002)
·
The International Conference on Harmonisation (ICH) harmonized tripartite guideline regarding
Good Clinical Practice (GCP) (E6 Consolidated Guidance, April 1996)
·
Code of Federal Regulation
·
Local Laws and Regulations
Sponsor Representative:
Bruce W Kovacs, MD
Afecta Pharmaceuticals
2102 Business Center Drive
Irvine, CA
92612
_____________________________ 
___________________
Sponsor Representative
Date


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INVESTIGATOR ACKNOWLEDGEMENT
INVESTIGATIONAL PRODUCT:
1.
Topical AFX 5931
STUDY TITLE:   “A Double-Blind, Pilot Study to Evaluate the Efficacy and Safety of Topical AFX 5931
in the Treatment of Mild to Moderate Hand Dermatitis”
PROTOCOL IDENTIFIER: CCCR 08-2018
I have read and understand this protocol, and will comply with the requirements for obtaining informed
consent from all study subjects prior to initiating any protocol-specific procedures, understand and abide
by the requirements for maintenance of source documentation, and provide assurance that this study will
be conducted according to all requirements as defined in this protocol, clinical study agreement, Code of
Federal Regulation, and all applicable regulatory requirements.
I also agree that persons debarred from conducting or working on clinical studies by any court or
regulatory agency will not be allowed to conduct or work on this study. I will immediately disclose it in
writing to the Sponsor if any person who is involved in the study is debarred, or if any proceeding for
debarment is pending, or, to the best of my knowledge, threatened.
This document contains confidential information of the Sponsor, which must not be disclosed to anyone
other than the recipient study staff and members of the IRB/EC. I agree to ensure that this information will
not be used for any purpose other than the evaluation or conduct of the clinical investigation without the
prior written consent of the Sponsor.
_________________________________________
__________________________
Principal Investigator
Date
Mark S. Nestor, M.D., Ph.D.
Director
Center for Clinical and Cosmetic Research
2925 Aventura Boulevard, Suite 205
Aventura, Florida 33180
nestormd@admcorp.com
Ph. (305) 933-6716


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PROTOCOL SYNOPSIS
Protocol Title:
A Double-Blind, Pilot Study to Evaluate the Efficacy and Safety of Topical AFX
5931 in the Treatment of Mild to Moderate Hand Dermatitis
Protocol Number:
CCCR 08-2018
Phase/Type:
Pilot - Investigator Initiated Trial (IIT)
Principal
Investigator:
Mark Steven Nestor, M.D., Ph.D.
Center for Clinical and Cosmetic Research
2925 Aventura Boulevard, Suite 205
Aventura, Florida 33180
Study Center(s):
One (1) study center in the United States:
Center for Clinical and Cosmetic Research
2925 Aventura Boulevard, Suite 205
Aventura, Florida 33180
Objectives:
Primary Objective:
1.
To measure the efficacy of topical AFX 5931 in the treatment of mild to
moderate hand dermatitis in subjects 12 years of age and older
Secondary Objective:
2.
To measure the tolerability and safety of topical AFX 5931 in the treatment of
mild to moderate hand dermatitis  in subjects 12 years of age and older
Study Design:
This is a double-blind, pilot study with 20 subjects to determine the tolerability and
efficacy of topical AFX 5931 in the treatment of mild to moderate hand dermatitis.
Subjects are screened up to 30 days before the baseline visit. Subjects who meet
the eligibility criteria may qualify for the study. Subjects will be randomized in a
3:1 ratio to receive either the active or vehicle medication. 15 subjects will receive
the active, therapeutic product and 5 subjects will receive the inactive, vehicle
product. Subjects will complete 4 study visits according to the following 4-week
timeline: Day [-30] – [-1] (Screening), Day 0 (Baseline), Day 14 (Follow-Up), Day
28 (Follow-up | ET | EOS). At Visit 2, IP will be dispensed and baseline readings
of efficacy as well as safety/tolerability assessments will be obtained prior to
application of the IP. Subjects will apply IP twice daily and compliance will be
monitored by periodically reviewing the subject diary. The evaluations that will be
used to measure efficacy of the product will be the Investigator’s Global
Assessment and Hand Eczema Severity Index. The Subject’s Local Dermal
Tolerability Assessment and Local Skin Reaction Assessment will be used
throughout the course of the study to evaluate tolerability. Additionally, the actions
that will be taken to evaluate safety will be the monitoring of adverse events, vital
signs, and changes in concomitant medications. Digital photographs will be taken
at each visit (excluding Visit 3).


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Inclusion Criteria:
1.
Subject is a male or non-pregnant female, 12 years of age and older.
2.
Subject is willing and able to provide written informed consent for the study.
3.
Subject is willing and able to apply the investigational product as directed,
comply with study instructions and commit to all follow-up visits for the
duration of the study.
4.
Subject has clinical diagnosis of mild to moderate hand dermatitis for at least 3
months.
5.
Subject has a baseline Investigator’s Global Assessment (IGA) score of 2 or 3
(disease severity of mild or moderate).
6.
Subject is in good general health and free of any disease state or physical
condition that might impair evaluation of hand dermatitis or which, in the
investigator’s opinion, exposes the subject to an unacceptable risk by study
participation.
7.
Women of childbearing potential (WOCBP) must use an effective method of
birth control or must be post-menopausal or surgically sterile.  Women of
childbearing potential (WOCBP) must have a negative urine pregnancy test
(UPT) at Baseline.
Exclusion
Criteria:
1.
Subject is pregnant, lactating, or is planning to become pregnant during the
study.
2.
Subject is currently enrolled in an investigational drug or device study.
3.
Subject has used an investigational drug or investigational device treatment
within 30 days prior to Visit 2/Baseline.
4.
Subject has active cutaneous bacterial or viral infection in any treatment area
(clinically infected hand dermatitis) at Visit 2/Baseline.
5.
Subject has used any of the following therapies within 30 days prior to Visit
2/Baseline:
•
Systemic corticosteroids (oral and injectable [intravenous and
intramuscular]) (Intranasal and Inhalational steroids are allowed if use
is kept constant during the study)
•
UVA/UVB therapy
•
PUVA (psoralen plus ultraviolet A) therapy
•
Immunomodulators or immunosuppressive therapies
•
Interferon
•
Cytotoxic drugs (e.g., methotrexate, cyclophosphamide, azathioprine)
•
Oral retinoids
6.
Subject has used any of the following therapies within 14 days prior to Visit
2/Baseline:
•
Systemic antibiotics
•
Topical calcipotriene or other topical vitamin D preparations
7.
Subject has used any of the following therapies within 7 days prior to Visit
2/Baseline:
•
Topical and oral antihistamines
•
Topical antibiotics
•
Topical corticosteroids
•
Topical antifungals
8.
Subject has a history of sensitivity to any of the ingredients in the
investigational product.


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9.
Subject is known to be noncompliant or is unlikely to comply with the
requirements of the study protocol (e.g., due to alcoholism, drug dependency,
mental incapacity) in the opinion of the investigator.
Investigational
Products:
Medication Name:
1.
Active Treatment: Topical AFX 5931
-
A medication combining a series of small, potent anti-inflammatory
molecules that down-regulate the CCL5/CCL2 pro-inflammatory
pathway
2.
Vehicle
Patient
Population:
-
20 healthy, adult male or non-pregnant female subjects
-
12 years of age and older
Safety Endpoints:
Safety/tolerability endpoints are monitored by members of the study staff. They
include the following:
-
Changes in local skin reaction
-
Changes in AEs and serious adverse events (SAEs)
-
Changes in vital signs and physical examinations
-
Changes in concomitant procedures/medications
-
Presence of signs/symptoms of irritation of the skin.
Statistical
Methods:
-
All analyses of the pooled individual patient data will be performed with the
use of SPSS software using a two-way Chi-square test analysis, t-tests, odds
ratios, and analysis of variance (ANOVA).
Assessments:
-
Hand Eczema Severity Index
o
Investigator-rated: clinical evaluation of both the extent and  intensity of
hand dermatitis
§
Clinical signs: erythema, infiltration/papulation, vesicles,
figures, scaling, and edema
§
Locations: fingertips, fingers (excluding tips), palms of hands,
backs of hands, wrists
§
Extent is graded on a visual 5-point scale
§
Intensity is graded on a visual 4-point scale
-
Local Skin Reaction Assessment
o
Investigator-rated: clinical grading score of erythema,
induration/papulation, and lichenification
§
Each parameter is graded on a visual 4-point scale
-
Subject’s Local Dermal Tolerability Assessment:
o
Subject-Rated: clinical grading score of pruritus
§
Each parameter is graded on a visual 4-point scale
-
See assessments reference at end
Randomization:
-
The subjects will be randomized to receive either the active or control
medication based on a 3:1 randomization scheme
-
Out of 20 total subjects, 15 will receive the active treatment while 5 will receive
the vehicle
Photography:
-
Digital photographs will be taken at proximal and distal views of the dorsal as
well as palmar surfaces of the hand


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3
OBJECTIVES
3.1 Primary and Secondary Objectives
Primary Objective:
1.
To measure the efficacy of topical AFX 5931 in the treatment of mild to moderate hand
dermatitis in subjects 12 years of age or older
a.
Assessed via Hand Eczema Severity Index
b.
Assessed via Investigator’s Global Assessment
Secondary Objective:
2.
To measure the tolerability and safety of topical AFXC 5931 in the treatment of mild to moderate
hand dermatitis in subjects 12 years of age or older
a.
Assessed via Subject’s Local Dermal Tolerability Assessment
b.
Assessed via Local Skin Reaction Assessment
c.
Assessed via changes in adverse events or concomitant medications
3.2
Overview
This is a double-blind, pilot study with 20 subjects to determine the tolerability and efficacy of topical
AFX 5931 in the treatment of mild to moderate hand dermatitis. Subjects are screened up to 30 days
before the baseline visit. Subjects who meet the eligibility criteria may qualify for the study. Subjects will
be randomized in a 3:1 ratio to receive either the active or control medication, in which 15 subjects will
receive the active, therapeutic product and 5 subjects will receive the inactive, vehicle product. Subjects
will complete 4 study visits according to the following 4-week timeline: Day [-30] – [-1] (Screening),
Day 0 (Baseline), Day 14 (Telephone Call), Day 28 (Follow-up | ET | EOS). At Visit 2, IP will be
dispensed and baseline readings of efficacy and safety/tolerability assessments will be obtained prior to
application of the IP. Subjects will apply IP twice daily and compliance will be monitored by reviewing
the subject diary periodically throughout the study. The assessments that will be used to evaluate efficacy
of the product will be the Hand Eczema Severity Index and Investigator’s Global Assessment. The
Subject’s Local Dermal Tolerability Assessment and Local Skin Reaction Assessment will be used
throughout the course of the study to evaluate tolerability. Additionally, the actions that will be taken to
evaluate safety will be the monitoring of any adverse events or concomitant medications. Digital
photographs will be taken at each visit (excluding Visit 3).


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4
STUDY POPULATION
4.1 Inclusion Criteria
Subjects who meet all of the following criteria are eligible for this study:
1.
Subject is a male or non-pregnant female, 12 years of age and older.
2.
Subject is willing and able to provide written informed consent for the study.
3.
Subject is willing and able to apply the investigational product as directed, comply with study
instructions and commit to all follow-up visits for the duration of the study.
4.
Subject has clinical diagnosis of mild to moderate hand dermatitis for at least 3 months.
5.
Subject has a baseline Investigator’s Global Assessment (IGA) score of 2 or 3 (disease severity of
mild or moderate).
6.
Subject is in good general health and free of any disease state or physical condition that might impair
evaluation of hand dermatitis or which, in the investigator’s opinion, exposes the subject to an
unacceptable risk by study participation.
7.
Women of childbearing potential (WOCBP) must use an effective method of birth control or must be
post-menopausal or surgically sterile.  Women of childbearing potential (WOCBP) must have a
negative urine pregnancy test (UPT) at Baseline.
4.2
Exclusion Criteria
Subjects who meet any of the following criteria are not eligible for this study:
1.
Subject is pregnant, lactating, or is planning to become pregnant during the study.
2.
Subject is currently enrolled in an investigational drug or device study.
3.
Subject has used an investigational drug or investigational device treatment within 30 days prior to
Visit 2/Baseline.
4.
Subject has active cutaneous bacterial or viral infection in any treatment area (clinically infected hand
dermatitis) at Visit 2/Baseline.
5.
Subject has used any of the following therapies within 30 days prior to Visit 2/Baseline:
•
Systemic corticosteroids (oral and injectable [intravenous and intramuscular]) (Intranasal and
Inhalational steroids are allowed if use is kept constant during the study)
•
Immunomodulators or immunosuppressive therapies
•
Interferon
•
Cytotoxic drugs (e.g., methotrexate, cyclophosphamide, azathioprine)
•
Oral retinoids
6.
Subject has used any of the following therapies within 14 days prior to Visit 2/Baseline:
•
Systemic antibiotics
•
Topical calcipotriene or other topical vitamin D preparations
•
Topical retinoids
7.
Subject has used any of the following therapies within 7 days prior to Visit 2/Baseline:
•
Topical and oral antihistamines
•
Topical antibiotics
•
Topical corticosteroids
•
Topical antifungals
•
Other topical drug products
8.
Subject has a history of sensitivity to any of the ingredients in the investigational product.


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9.
Subject is known to be noncompliant or is unlikely to comply with the requirements of the study
protocol (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the
investigator.
4.3
Withdrawal and Replacement of Patients
Patients who withdraw consent must be withdrawn from the study. No justification for such a decision is
required. Patients must be withdrawn from the study if the investigator considers it in the best interest of
the patient that he/she be withdrawn. Patient must notify the principal investigator in writing at the time
of their decision. The reasons for withdrawal must be recorded, if available, on the case report form
(CRF) and in the patient’s medical records. If possible, a complete, final examination should be
performed on all patients who withdraw from the study. Patients who are withdrawn will not be replaced.
4.4
Patient Identification
All patients enrolled must be identifiable throughout the study. The investigator will maintain a personal
list of patient numbers and patient names to enable records to be found at a later date.
Subjects will receive a patient number as detailed in a separate document located in the investigator’s file.
Patients who terminate their study participation for any reason after signing the consent form, regardless
of whether study medication was taken or not, will retain their patient identification number. In that case,
the next patient identification number and bottle in the sequence are to be used. The following patient is
given the next patient identification number. Screen failures will not be assigned a patient identification
number. Screen failures are not to interrupt the patient identification schema for the enrolled subjects.


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5
STUDY MEDICATION
5.1
Identity
Trade Name:
AFX 5931
Manufacturer:
Afecta Pharmaceuticals
5.2
Maintaining the Blind
The subjects will be randomized to receive one of two treatments (active vs. control) in a 3:1 ratio. Thus,
out of the total 20 subjects, 15 subjects will receive the active “AFX 5931” medication while 5 subjects
will receive the vehicle product. Separate study staff members are assigned to administer the study
medication versus conduct study evaluations.
5.3
Administration
The subject will be instructed on how to apply the IP independently for use throughout the rest of the
study at the baseline visit (Visit 2).
5.4
Compliance
Subject compliance is based on attending every required study visit and completing applications of the
medication twice daily starting from the baseline visit. Subjects will be required to qualify for the study
honestly and return for all study visits. Subject will be required to fill out a record of IP applications on a
subject diary, which must be filled out throughout the study. Any missing of visits or doses may qualify
for withdrawal from the study under the Principal Investigator’s discretion.
5.5
Concomitant Medications and Treatments
All medications or treatments ongoing at the screening visit or taken within the previous 30 days must be
recorded on the prior and concomitant medications CRF.
Any medication the patient takes during his or her study participation is considered a concomitant
medication. This applies to prescription and over-the-counter (OTC) drugs and to herbal supplements,
whether taken systemically or applied topically. In addition, any treatment the patient receives other than
the study medication is considered a concomitant treatment. All concomitant medications and
concomitant treatments must be recorded in the CRFs.  Prohibited medication classes and treatments are
described in the Exclusion Criteria. In the event that a prohibited treatment is received, it must be
documented on the CRFs.
Subjects will not be allowed to use any of the prohibited medications listed in the exclusion criteria
during the course of this study and up to 30 days prior to the start of the study. Subjects will be allowed
the use of birth control, vitamins, or supplements.


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6
VARIABLES AND METHODS
6.1
Safety
6.1.1
Adverse Events
Illnesses present at study entry are considered pre-existing conditions and will be documented as medical
history on the CRF provided. All adverse events, including intercurrent illnesses and worsening of pre-
existing conditions, must be reported and documented as described below.
6.1.1.1
Definitions
An adverse event is any untoward medical event that occurs in a patient or subject administered a
pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An
AE can therefore be any unfavorable and unintended sign (including abnormal laboratory findings),
symptom, or disease temporally associated with the investigational product, whether or not related to the
investigational product.
6.1.1.2
Assessment of Adverse Events
Volunteered, observed, and elicited reports of adverse events will be recorded. This includes adverse
events the patient reports spontaneously, those the investigator observes, and those the investigator elicits
in response to open-ended questions at the times indicated on the Schedule of Observations. At each visit,
the patient should be asked a non-leading question such as: “Do you feel different in any way since your
last treatment visit?” Subjects will also be questioned concerning possible skin reactions according to a
specific checklist of possible adverse events.
Each adverse event will be assessed by the investigator with regard to the following categories.
Serious/Not Serious
International Conference on Harmonization (ICH) Guidelines and US Federal Regulations define a
serious adverse event (SAE) as any untoward medical occurrence that at any dose:
§
Results in death.
§
Is life-threatening. This means that the patient is at risk of death at the time of the event; it does
not mean that the event hypothetically might have caused death if it were more severe.
§
Requires or prolongs hospitalization (hospitalization defined as ³24 hours).
§
Results in persistent or significant disability or incapacity.
§
Is a congenital anomaly or birth defect.
§
Important medical events that may not be immediately life-threatening or result in death or
hospitalization, but that may jeopardize the patient or require intervention to prevent one of the
above outcomes, usually should also be considered serious. Events are considered serious if they
result in life threatening events, death, genetic abnormality, persistent disability, or prolonged
hospitalization. Examples include pregnancy, allergic bronchospasm requiring treatment at home
or in the emergency room, and blood dyscrasias or convulsions not resulting in hospitalization.
Medical and scientific judgment should be used to determine whether such events should be
considered serious.


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§
Pregnancy should always be considered as a serious adverse event. As such, pregnancy should be
recorded on the adverse event page of the CRF and a serious adverse event form completed and
submitted as described.
Serious adverse events will be reported to the IRB/sponsor no more than 7 business days from the
beginning of the event.
Severity
The severity of each adverse event must be assessed and recorded on the Adverse Event CRF as mild,
moderate, or severe.
Mild:
An adverse event that is usually transient, requires no special treatment, and does not
interfere with usual activities.
Moderate:
An adverse event that interferes with usual activities but may be ameliorated by
therapeutic measures.
Severe:
An adverse event that is intense or debilitating and that interferes with usual
activities. Recovery is usually aided by therapeutic measures and may require the
discontinuation of study medication.
Relationship to Study Treatment
The investigator will assess the relationship between the study medication and the adverse event as
probable, possible, unlikely, or unrelated as follows.
Probable:
Reports including good reasons and sufficient information to assume a causal
relationship in the sense that it is plausible, conceivable, or likely.
Possible:
Reports containing sufficient information to indicate the possibility of a causal
relationship in the sense of it not being impossible and not unlikely, although the
connection may be uncertain or doubtful (e.g., due to missing data, insufficient
evidence, etc.).
Unlikely:
Reports of a clinical event, including laboratory test abnormality, with a temporal
relationship to drug administration which makes a causal relationship improbable,
and in which other drugs, chemicals, or underlying disease provide plausible
explanations.
Not Related:
Reports excluding the possibility of a relationship between the event and the drug
treatment, i.e., no reasonable suspected causal relationship to study medication
administration.
6.1.1.3
Recording Adverse Events
All adverse events, regardless of relationship to study treatment, must be recorded on the Adverse Event
CRF. All adverse events reports should contain the date the adverse events occurred, a brief description of
the event, time of onset, end date or duration of event (if less than 24 hours), intensity, treatment required,
relationship to study treatment, action taken, outcome, and whether the event is classified as serious.


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6.1.1.4
Follow-Up of Adverse Events
Reporting of adverse events will terminate on the last day of study follow-up. The investigator must
follow non-serious events possibly related to the study treatment and all serious adverse events until they
resolve or until the investigator assesses them as chronic or stable.
6.1.1.5
Protocol Deviations Due to an Emergency or Adverse Event
Deviations from the protocol will be determined as allowable on a case-by-case basis. All protocol
deviations and the reasons for such deviations must be noted on the CRF.
6.1.1.6  
Study Medication and Treatment
The medication that a subject will be randomized to apply throughout the study will either be the active
investigational product (AFX 5931) or the inactive vehicle product. After applying the IP for the first time
at the clinic/study site under supervision of the health staff, subjects will, subsequently, be responsible for
applying the treatment independently (twice daily) and recording each application on a subject diary.
6.1.1.7
Photography
Digital photographs will be taken at proximal and distal views of both the dorsal as well as palmar
surfaces of the subject’s hand (treatment area).
6.2
Laboratory Variables
Laboratory variables are not applicable to this study.


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6.3
Schedule of Visits:
CCCR 08-2018
Visit 1
Visit 2
Visit 3
Visit 4
n=20
Day [-30] – [-1]
Day 0
Day 14
Day 28
Study Assessments
±1 Day
± 2 Days
± 3 Days
Informed Consent
X
Demographics
X
Inclusion/Exclusion
Criteria
X
Medical/Dermatological
History
X
Fitzpatrick Skin Phototype
X
Brief Physical
Examination
X
X
Vital Signs
X
X
UPT for WOCBP
X
Hand Eczema Severity
Index
X
X
X
X
Investigator’s Global
Assessment
X
X
X
X
Local Skin Reaction
Assessment
X
X
X
Subject’s Local Dermal
Tolerability Assessment
X
X
X
Apply Investigational
Product (IP)
X
X
X
IP Accountability
(Dispensing/Collecting)
X
X
X
Subject Diary
(Dispense/Review/Collect)
D
R
R/C
Digital Photographs
X
X
X
X
Concomitant
Medications/Therapies
X
X
X
X
Adverse Events
X
X
X
X
Exit Case Report Form
X


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6.4
Observations by Visit
6.4.1       Visit 1 (Day -30 to -1): Screening
Subjects can be screened up to 30 days prior to Visit 2/Baseline. If applicable, qualified subjects can
washout from prohibited medications and/or therapies prior to Baseline (after obtaining consent). Subjects
who require screening period or washout for longer than 30 days will be re-consented but may still be
enrolled in the study if they otherwise meet enrollment criteria.
The study requirements and procedures will be reviewed and written informed consent must be obtained
prior to the initiation of any study-related procedures. Demographics, inclusion/exclusion criteria,
medical/dermatological history, and concomitant medications and therapies will be reviewed to determine
eligibility. A brief physical exam will be performed, vital signs will be taken, and Fitzpatrick Skin
Phototype will be determined. The Hand Eczema Severity Index and Investigator’s Global Assessment
will be completed. Digital photographs will be taken at proximal and distal views of both the dorsal as
well as palmar surfaces of the subject’s hand (treatment area). The subject will be scheduled for Visit 2
(Baseline).
6.4.2
Visit 2 (Day 0): Baseline
The subject will return to the clinic and will be queried for any changes in health status since the previous
visit, including concomitant medications and therapies. A urine pregnancy test with negative result
confirmed will be performed for all WOCBP. The Hand Eczema Severity Index and Investigator’s Global
Assessment will be completed. Baseline reading of local skin reactions will be assessed prior to IP
application. The Subject’s Local Dermal Tolerability Assessment will be performed. IP will be dispensed
to the subject. IP will then be dispensed and subject will apply the first dose in clinic. The subject diary
will be dispensed. Digital photographs will be taken at proximal and distal views of both the dorsal as
well as palmar surfaces of the subject’s hand (treatment area). The subject will be scheduled to return to
clinic for Visit 3 in accordance with the treatment window.
6.4.3
Visit 3 (Day 14): Follow-Up
The subject will return to the clinic and will be queried for any changes in health status since the previous
visit, including concomitant medications and therapies. The Hand Eczema Severity Index and
Investigator’s Global Assessment will be completed. Local skin reactions will be assessed. The Subject’s
Local Dermal Tolerability Assessment will be performed. IP will be dispensed at the beginning of the
study and collected at the end of the study. IP will be applied by the subject at home in the evening,
consistent with their usual twice daily dosing. The subject diary will be reviewed. Digital photographs
will be taken at proximal and distal views of both the dorsal as well as palmar surfaces of the subject’s
hand (treatment area). The subject will be scheduled to return to clinic for Visit 4 in accordance with the
treatment window.
6.4.4
Visit 4 (Day 28): Ending Follow-Up | ET | EOS
The subject will return to the clinic and will be queried for any changes in health status since the previous
visit, including concomitant medications and therapies. A brief physical exam will be performed and vital
signs will be taken. The Hand Eczema Severity Index and Investigator’s Global Assessment will be
completed. Local skin reactions will be assessed. The Subject’s Local Dermal Tolerability Assessment
will be performed. IP will be dispensed at the beginning of the study and collected at the end of the study.
IP is to be applied at least once before the subject comes in for the scheduled visit. The subject diary will


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be reviewed and collected. Digital photographs will be taken at proximal and distal views of both the
dorsal as well as palmar surfaces of the subject’s hand (treatment area).
6.5
Study Termination
If the study sponsor or investigator discovers conditions arising during the study that indicate the study
should be halted, the study must be terminated after appropriate consultation between the study sponsor,
project manager, and investigator. Conditions that may warrant termination include, but are not limited to,
the following – the discovery of an unexpected, significant, or unacceptable risk to the subjects enrolled
in the study, insufficient adherence to protocol requirements.
7
DATA HANDLING AND RECORD KEEPING
7.1
Archiving Study Records
Essential documents should be retained on site for a minimum of 2 years after the last approval of a
marketing application in an ICH region and until there are no pending or contemplated marketing
applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product.  Once the 2 years have elapsed, essential documents will be
transferred off site to a secure location and retained for up to 7 years.  The documents will be retained for
a longer period if required by the applicable legal and regulatory requirements.
7.2
Statistical Methods
7.2.1
General Statistical Methods
All data collected during the study will be presented in data listings. Summary tables and analyses will be
based on the following analysis populations:
Safety population:
All enrolled subjects who received study treatment.
Intention-to-treat (ITT)
population:
All enrolled subjects, regardless of whether they received
study treatment.
Per protocol (PP) population:
All subjects in the ITT population for whom no major protocol
violations occurred.
The primary population for analyses of efficacy data will be ITT population. A supportive analysis will be
presented for the PP population if this is significantly different from the ITT population. The assessment
of safety will be based on the safety population.
Continuous data will be summarized by treatment group using descriptive statistics (number, mean,
median, standard deviation, minimum, and maximum). Categorical data will be summarized by treatment
group using frequency tables (frequencies and percentages). Ninety-five percent confidence intervals will
be constructed for proportions of successes.
Statistical tests will be used for analysis. The analysis will be 2-sided and conducted at the 0.05
significance level. An analysis of means using an independent samples t-test and ANOVA will be used.
Primary analysis will be completed with the help of a chi-square analysis and assessment of relative risk
and odds ratios.


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7.2.2
Sample Size
The total sample size needed is 20 subjects that are 12 years of age and older. Each subject will be
randomized in a 3:1 ratio to receive either the active (15 subjects) or vehicle (5 subjects) product
throughout the study. Endpoints will be evaluated using a 2-sided Chi-square test and t-test at the 0.05
significance level.
7.2.3
Interim Analyses
An Interim Analyses is not applicable.
7.2.4
Missing Data
Missing data will be left blank.
7.2.5
Patient Disposition
The numbers and percentages of enrolled subjects who completed the study and discontinued from the
study will be provided, as well as reasons for earlier discontinuation.
7.2.6
Treatment Compliance
Subjects will complete a subject diary recording daily applications of the medications to the treatment
area on the face. Each medication is to be applied twice daily.
7.2.7
Concomitant Medications and Treatments
A log of medications taken and procedures performed during the study will be recorded for each subject.
7.2.8
Efficacy Analyses
Efficacy variables will be analyzed at the time points shown in the visit schedule.
7.2.8.1
Primary Efficacy Analyses
This study is concerned with the efficacy of topical AFX 5931 in the treatment of mild to moderate hand
dermatitis. Changes in clinical scores recorded via the Hand Eczema Severity Index and Investigator’s
Global Assessment will be the primary modes of efficacy evaluation.
7.2.8.2
Safety Analyses
Safety analyses will be performed on the safety population. The Local Skin Reaction Assessment and the
Subject’s Local Dermal Tolerability Assessment will be the primary modes of tolerability evaluation.
Monitoring the record of AEs and changes in concomitant medication throughout the course of the study
will be the primary mode of safety evaluation. In addition, the frequency and percentage of subjects with
adverse events will be summarized by coded body system and preferred term for each treatment group
using the Medical Dictionary for Regulatory Activities (MedDRA). At each level of summarization
(global, body system, and preferred term), a patient will be counted once if he/she has reported one or
more AEs at that level. Tabular summaries will be presented for all adverse events, by severity, by


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relationship to treatment, and for serious adverse events. No statistical testing will be performed. Changes
in concomitant medications/procedures will also be monitored.
7.3
Source Documents
The full dataset will be collected for all subjects enrolled. All required data for this study will be collected
on paper source document worksheets. The collected data will be entered into a validated database.
Database lock will occur once quality assurance procedures have been completed.
Source data is all information, original records of clinical findings, observations, or other activities in a
clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in
source documents. Examples of source documents include hospital records, office charts, memoranda,
evaluation checklists, photographs, and subject files.
All procedures for the handling and analysis of data will be conducted using good computing practices
meeting USFDA guidelines for the handling and analysis of data for clinical trials.
7.4
Data Capture
Data will be captured on CRFs. CRFs are the primary data collection instrument for the study. All data on
the CRF will be recorded, and all missing data must be explained. All data collected for the study and
entered into the CRF must be traceable to a source document.
The Investigator will review, approve, and sign off on the CRFs. The Investigator’s signature will serve
as a testament of the Investigator’s responsibility for ensuring that all clinical data entered on the CRF are
complete, accurate, and authentic. The CRF data is entered into a validated database.
8
ETHICAL, LEGAL AND QUALITY ADMINISTRATIVE ASPECTS
8.1
Good Clinical Practice
The procedures set out in this study protocol are designed to ensure that the individual treatments as well
as the investigator abide by the principles of the Good Clinical Practice (GCP) guidelines of the ICH. The
study will be carried out to abide with local legal and regulatory requirements.
Both Sponsor and Principal Investigator confirm this by signing this study protocol (see Page 2-3).
8.2
Changes in Statistical Methods
All changes in statistical methods that are described in the statistical analysis plan (SAP) will be
documented in the clinical study report.
8.3
Informed Consent
Before being admitted to the study, informed consent will be obtained from each patient (or his/her
legally authorized representative) according to the regulatory and legal requirements of the United States.
This consent form must be dated and retained by the investigator as part of the study records.


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Should a protocol addendum be made, the patient consent form may be revised to reflect the changes of
the protocol.
If the consent form is revised, it is the responsibility of the investigator to ensure that an amended consent
is reviewed and approved by the IRB. The approved amended consent form should be signed by all
subjects subsequently entered in the study and those currently in the study.
The investigator will not undertake any investigation specifically required only for the clinical study until
valid consent has been obtained. The terms of the consent and when it was obtained must also be
documented in the CRF.
8.4
Approval of Study Protocol
Upon finalization of the original study Protocol, the Investigator Signature Page and Sponsor Signature
Page are to be executed by each party representative as an acceptance and agreement of the Protocol.
Before the start of the study, the study protocol and/or other appropriate documents will be submitted to
the IRB in accordance with local legal requirements.
The sponsor and the investigator must inform each other in writing that all ethical and legal requirements
have been met before the first patient is enrolled in the study.
8.5
Confidentiality
All study findings and documents will be regarded as confidential.
The anonymity of participating subjects must be maintained. Subjects will be identified on CRFs and
other documents by their initials, birth date, and patient number.
8.6
Ethics Committee and Regulatory Authorities
Before enrollment of subjects into this study, the protocol, ICF and any promotional material or
advertisements will be reviewed and approved by the appropriate IRB and regulatory authorities, where
applicable.  The study will commence only when the committee has approved the protocol or a modification
thereof and a copy of the approval letter is received.
It is the investigator’s responsibility to obtain IRB approval for the protocol and all subsequent major
changes, in compliance with local law.
8.7
Monitoring
The study monitor and/or other authorized representatives of the Sponsor is/are responsible for monitoring
that each study site conducts the study according to the protocol, SOPs, other written instructions, Code of
Federal Regulation (Title 21, CFR Part 812) and applicable regulatory guidelines. The investigator will
permit the study monitor or other authorized representatives to visit the study site at appropriate intervals to
observe the progress of the study, review study records/documentation, and ensure that informed consent has
been obtained for each subject prior to performing any study procedure.


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8.8
Auditing
The Sponsor and/or Sponsor’s representatives may conduct audits (quality assurance) to evaluate study
conduct and compliance with the protocol, SOPs, other written instructions/agreements, Code of Federal
Regulation (Title 21, CFR Part 812) and applicable regulatory guidelines/requirements. The investigator will
permit auditors to visit the study site. The quality assurance auditor will have access to all medical records,
the investigator’s trial-related files and correspondence, and information in the informed consent
documentation of this clinical trial.


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9.0
Research Study Assessments
Primary Endpoint Evaluations
Hand Eczema Severity Index:
Reference: Held et al – British Journal of Dermatology – Volume 152 Issue 2 (2005) pages 302-307
Each hand is divided into five areas [fingertips, fingers (except the tips), palms, back of hands and wrists].
The clinical signs of erythema, induration/papulation, vesicles, fissuring, scaling and oedema are graded
on the following scale:
0 = no skin changes
1 = mild disease
2 = moderate
3 = severe
Per each location (combining both hands), the affected region was given a score for extent of surface area
involvement on the following scale:
 0 = 0%;
1 = 1–25%
2 = 26–50%
3 = 51–75%
4 = 76–100%
Finally, the score given for the extent at each location was multiplied by the sum of the intensity of
clinical features. The total sum (HECSI score, highlighted above) was calculated, ranging from 0 to a
maximum severity score of 360.
Clinical Signs
Fingertips
Fingers
(except tips)
Palms of
Hands
Backs of
Hands
Wrists
Erythema (E)
Infiltration (I)
Vesicles (V)
Fissures (F)
Scaling (S)
Oedema (O)
SUM
Extent
Total HECSI
Score = ______
SUM *
Extent
SUM *
Extent
SUM *
Extent
SUM *
Extent
SUM *
Extent


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Investigator’s Global Assessment:
The investigator will rate the subject’s hand dermatitis on a visual 5-point scale as follows:
0: Clear:
No signs of HE
1: Almost clear:
Just perceptible scaling and/or erythema;
2: Mild disease:
Mild scaling and/or mild erythema, and/or mild cracking
3: Moderate disease:
Moderate scaling and/or erythema, and/or moderate cracking/fissuring
4: Severe disease:
Severe scaling and/or severe erythema, and/or severe cracking/fissuring
Dorsal and palmar surfaces of the hand are evaluated together.
Reference: Diamant et al. - Dermatology Basel - Volume 207, Issue 1 (2003) pages 37-42
Secondary Endpoint Evaluations
Subject’s Local Dermal Tolerability Assessment:
The subjects will be asked to grade their feeling of itching at the application site using a 4-point
tolerability scale, where 0=None, 1= Mild, 2= Moderate, and 3=Severe.
Pruritus:
Definition: itching
0 = None:
No itching
1 = Mild:
Occasional, slight itching/scratching
2 = Moderate:
Constant or intermittent itching/scratching/discomfort that is not disturbing sleep
3 = Severe:
Bothersome itching/scratching/discomfort that is disturbing sleep
Local Skin Reaction Assessment:
The investigator or designee will describe his/her assessment of the subject’s hands at the moment using a
4-point tolerability scale, where 0=None, 1=Mild, 2=Moderate, and 3=Severe.
Erythema:
Definition: abnormal redness of the skin
0 = None:
No erythema
1 = Mild:
Slight pinkness present
2 = Moderate:
Definite, dull redness that is clearly distinguishable
3 = Severe:
Intense, deep redness
Induration/Papulation:  Definition: inflammation, swelling
0 = None:
No elevation
1 = Mild:
Slightly perceptible elevation
2 = Moderate:
Clearly perceptible elevation but not extensive
3 = Severe:
Marked and extensive elevation
Lichenification:
Definition: thickening upper layers of skin
0 = None:
No thickening


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1 = Mild:
Slight thickening of the skin discernible only by touch and with skin markings
minimally exaggerated
2 = Moderate:
Definite thickening of the skin with skin markings exaggerated so that they form
a visible crisscross pattern
3 = Severe:
Thickened, indurated skin with skin markings visibly portraying an exaggerated
crisscross pattern

ICF_002.pdf: