Open Label Evaluation of the Adrenal Suppression Potential and Pharmacokinetic Properties of Twice Daily Halobetasol Propionate Foam, 0.05% in Subjects 12 to Less Than 18 Years of Age With Plaque Psoriasis Receiving Two Weeks of Treatment
Phase: PHASE4
Conditions: Plaque Psoriasis
Sponsor: Mayne Pharma International Pty Ltd

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
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PROTOCOL SYNOPSIS
Title
An Open Label Evaluation of the Adrenal Suppression Potential and 
Pharmacokinetic Properties of Twice Daily Halobetasol Propionate Foam, 
0.05% in Subjects 12 to Less Than 18 Years of Age with Plaque Psoriasis 
Receiving Two Weeks of Treatment
Study Type
Phase 4 in the United States (US) sites, Phase 2 in the non-US sites, as 
necessary.
Test Article
Halobetasol Propionate (HBP) Foam, 0.05%
Study Objective
The objective of this study is to determine the adrenal suppression potential 
and the pharmacokinetic (PK) properties of HBP Foam, 0.05% applied twice 
daily in subjects who are 12 to less than 18 years of age with stable plaque
psoriasis.  
Study Design
An open label, multicenter study.
Treatment Groups
All subjects will receive HBP Foam, 0.05%.
Duration of Treatment
Up to two weeks.
Duration of Study
Participation in the study is a minimum of five weeks (at least 20 days 
between Screening and Baseline Visits, up to two weeks of treatment, and 
potential follow-up for any subjects who have evidence of hypothalamic-
pituitary-adrenal [HPA] axis suppression).
Study Population
Male and female subjects 12 to less than 18 years of age with stable plaque 
psoriasis.
Total Number of 
Subjects
Subject enrollment will continue until at least 20 subjects with both 
Screening and End of Study (EOS) serum cortisol data (pre- and post-
cosyntropin stimulation) have completed the study without any significant 
protocol violations (evaluable subjects). This may require the enrollment of 
approximately 25 subjects.
Number of Sites
Approximately 12 sites in the US and Europe will participate in the study.
Inclusion Criteria
To enter the study, a subject must meet the following criteria: 
1.
Subject is male or non-pregnant female and is 12 to less than 18 years 
of age (i.e., at least 12 years old, but not yet reached their 18th birthday 
at the time of enrollment). 
2.
Subject has provided written informed assent and was accompanied by 
the parent or legal guardian at the time of assent/consent signing. The 
parent or legal guardian has provided informed consent for the subject. 
If a subject becomes 18 years of age during the study, the subject must 
provide written informed consent at the next study visit to continue study 
participation.

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
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3.
Subject has a clinical diagnosis of stable plaque psoriasis involving a 
minimum of 10% body surface area (BSA)1 (excluding the face, scalp, 
groin, axillae, and other intertriginous areas).
4.
Subject has an Investigator’s Global Assessment (IGA) score of at least 
three (3 = moderate) at the Baseline Visit.
5.
Subject is willing and able to apply the test article as directed, comply 
with study instructions, and commit to all follow-up visits for the 
duration of the study.
6.
Females must have a negative urine pregnancy test (UPT)2 at the 
Screening (Part B) and Baseline Visits and agree to use an effective form 
of birth control34 for the duration of the study.
Exclusion Criteria
A subject is ineligible to enter the study if he/she meets one or more of the 
following criteria: 
1.
Subject has spontaneously improving or rapidly deteriorating plaque 
psoriasis.
2.
Subject has guttate, pustular, erythrodermic, or other non-plaque forms 
of psoriasis.
3.
Subject has a physical condition which, in the investigator’s opinion, 
might impair evaluation of plaque psoriasis, adrenal axis function (e.g., 
Addison’s Disease, Cushing’s Syndrome) or which exposes the subject 
to an unacceptable risk by study participation.
4.
Subject has used any phototherapy (including laser), photo-
chemotherapy, or systemic psoriasis therapy including methotrexate, 
retinoids, cyclosporine, or biologics within 30 days prior to the initiation 
of treatment with the test article.
5.
Subject has used systemic corticosteroids (including oral or 
intramuscular) or topical, inhaled, or intranasal corticosteroids within 30 
days or 14 days, respectively, prior to Part B of the Screening Visit 
and/or the subject has used systemic or topical corticosteroids between 
Part B of the Screening Visit and the initiation of treatment.
6.
Subject has had prolonged exposure to natural or artificial sources of 
ultraviolet radiation within 30 days prior to the initiation of treatment or 
is intending to have such exposure during the study that is thought by 
the investigator to likely modify the subject's disease.
1 For this evaluation 1% BSA is approximately equivalent to the area of the subject’s closed hand (palm and 
fingers held together).  
2 UPT must have a minimum sensitivity of 25 mIU ß-HCG/mL.
3 Effective forms of birth control include a) hormonal contraceptives [e.g., oral, transdermal, injectable, 
implantable, or vaginal ring] (see next footnote), b) intrauterine device (IUD) for at least one week prior to 
test article application, c) barrier methods [condom and spermicidal or diaphragm/cervical cap and 
spermicidal], d) monogamous relationship with a partner who is sterile [e.g., vasectomy performed at least 
six months prior to study entry], or e) total abstinence for subjects who are not sexually active. Subjects who 
become sexually active or begin to have relations with a partner who is not sterile during the study must agree 
to use an effective form of birth control for the duration of the study.
4 Females taking hormonal therapy must be on treatment prior to study entry, continued per label, and must 
not change their dosing regimen during the study; treatment must be for (1) oral: at least one complete cycle 
(e.g., four to eight weeks); (2) transdermal, injectable (e.g., Depo-Provera), implantable or vaginal ring (e.g., 
NuvaRing): at least one week.

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
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7.
Subject has used topical psoriatic therapy including tar, anthralin, 
retinoids, vitamin D analogs (e.g., Dovonex®) within 14 days prior to 
the initiation of treatment with the test article.
8.
Subject has used emollients/moisturizers on areas to be treated within 
one day prior to the initiation of treatment with the test article.
9.
Subject is currently using lithium or Plaquenil (hydroxychloroquine).
10. Subject is currently using a beta-blocking medication (e.g., propranolol) 
or angiotensin converting enzyme inhibitors (e.g., lisinopril) at a dose 
that has not been stabilized, in the opinion of the investigator.
11. Subject has a history of sensitivity to any of the ingredients in the test 
article (see Section 6.1).
12. Subject is pregnant, lactating, or is planning to become pregnant during 
the study.
13. Subject is currently enrolled in an investigational drug or device study.
14. Subject has used an investigational drug or investigational device 
treatment within 30 days prior to Visit 1 (Screening).
15. Subject has been previously enrolled in this study and treated with the 
test article.
16. Subject has an irregular sleep schedule or works night shifts (cortisol 
levels exhibit physiological diurnal variation).
17. Subject has a screening Cosyntropin Stimulation Test (CST) with a post 
30-PLQXWHVWLPXODWLRQFRUWLVROOHYHORIJG/
18. 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. 
Study Procedures
The following procedures will take place according to the visit schedule:
Visit 1 (Screening Visit) (Day -20 or longer): At Visit 1 (Screening Visit), 
study procedures will be explained by the study coordinator and the subject 
must provide written informed assent and be accompanied by the parent or 
legal guardian at the time of assent/consent signing. The parent or legal 
guardian must provide informed consent for the subject. Consent/assent must 
be signed prior to the initiation of any study-related procedures. At this visit, 
consenting/assenting subjects will have their demographics and medical 
history, 
including 
concomitant 
medications, 
recorded 
and 
Inclusion/Exclusion (I/E) criteria, including percent BSA affected with 
disease, reviewed to determine subject eligibility. Subjects requiring a wash-
out period will be asked to return to complete the following procedures of 
Screening Visit (Part B) once the wash-out is completed. All female subjects 
must have a negative UPT to be eligible for this study. Vital signs, height 
and weight, as well as IGA score, will be recorded. Blood and urine samples 
will be taken for clinical laboratory tests (chemistry, hematology, and 
urinalysis). Subjects will have a Screening CST that will be initiated between 
7 to 9AM to determine their adrenal system response. A Screening PK 
sample for drug concentration in plasma will be collected in all subjects in 
conjunction with the Screening CST. Any adverse events (AEs) will be 
recorded. Enrollment into the treatment phase of the study (Baseline Visit) 
should be timed such that the Screening CST will be performed a minimum 
of 28 days before the projected end of the study phase. To accommodate this 
requirement, the Baseline Visit should ideally be scheduled at least 20 days 

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
Page 7 of 94 
TI SOP 305-A Protocol Template, Version 06
after the Screening Visit. The subject will be scheduled for the Day 
1/Baseline Visit.
Visit 2 (Day 1/Baseline Visit): At Visit 2 (Day 1/Baseline Visit), subjects 
with a normal response to CST (post-stimulation serum cortisol > 18 μg/dL) 
and who continue to meet all the other I/E criteria will be enrolled in the 
study while subjects with significant abnormal screening results (particularly 
CST results; post-VWLPXODWLRQ VHUXP FRUWLVRO   JG/ ZLOO EH
discontinued as screen failures. Review clinical laboratory tests (chemistry, 
hematology, and urinalysis); repeat any lab findings that are abnormal and 
deemed clinically significant by the investigator per protocol to confirm the 
findings. Study staff will reconfirm medical history and will record any 
changes in concomitant medications. All female subjects must have a 
negative UPT to continue in the study. A limited physical examination 
including vital signs and weight will be performed and photographs 
(optional) will be taken. IGA score will be recorded. Study staff will 
document percent BSA affected with disease in the Treatment Area and the 
percent BSA to be treated with the test article during the study. Baseline local 
skin reactions (LSRs) will be recorded prior to test article application. The 
weight of the canisters will be measured prior to dispensing and test article 
accountability will be documented. All eligible subjects will apply the first 
dose in the clinic and be instructed to apply the assigned test article twice 
daily (approximately every 12 hours) to the psoriatic plaques designated by 
the investigator until Day 15. Each subject will be given a Subject Instruction 
Sheet and the study personnel will demonstrate how and where to dispense 
and apply test article to all the psoriatic plaques within the Treatment Area. 
The total dose of test article applied per week should be a maximum of 
approximately 50 grams/week. Any AEs or LSRs (i.e., burning/stinging 
only) post-application will be recorded. A Subject Diary will also be given 
to each subject with completion instructions. The subject will be scheduled 
for the Day 8 visit. Prior to the Day 8 visit, subjects will be requested to i) 
apply the test article at bedtime on Day 7 and record the time, then ii) 
withhold application of the test article on the morning of the visit (Day 8).  
Visit 3 (Day 8 ± 1): If the subject’s psoriatic lesions within the Treatment 
Area are not completely clear, then the subject will complete these Visit 3 
(Day 8 ± 1) procedures. However, if the subject’s psoriatic lesions within the 
Treatment Area are completely clear per the Investigator’s assessment (i.e., 
IGA=0), then the subject will complete the Visit 4/EOS procedures; if the 
CST cannot be performed on Day 8, then the subject will complete Visit 3 
procedures, continue dosing of test article, and return on Day 9 (see Optional 
Visit) to complete the EOS procedures. Subjects who are clear at Day 8, 
complete CST on Day 8 (or Day 9), and have all EOS procedures completed 
on Day 8 (or Day 9) will exit the study at Day 8 (or Day 9) following a 
normal CST result.
Subjects will return to the clinic on Day 8 for the study staff to record IGA 
score, percent BSA affected with disease in the Treatment Area, percent 
BSA to be treated, review test article compliance (i.e., Subject Diary will be 
collected, reviewed, and dispensed, as necessary), and collect information on 
concomitant medications, AEs, and LSRs. Test article accountability will be 
documented.

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
Page 8 of 94 
TI SOP 305-A Protocol Template, Version 06
Subjects will have blood drawn on the morning of Day 8 to assess drug 
concentrations in plasma (trough values - ~12 hours after previous dose). 
Subjects will apply their morning dose at the clinic after the Day 8 trough 
blood sample is drawn and continue twice daily (approximately every 12 
hours) application of the test article until the next clinic visit. Any AEs or 
LSRs (i.e., burning/stinging only) post-application will be recorded. The 
subject will be scheduled for the next visit.
Day 9 (Optional Visit - for Subjects that are clear at Visit 3, Day 8): On the 
following day (Day 9), subjects cleared by Day 8 who could not have a CST 
performed on Day 8 will have a UPT (females only) and have a CST 
performed within ± 1 hour of Screening CST and should, to the extent 
possible, be initiated between 7 and 9AM. Photographs (optional) will be 
taken. Any AEs and LSRs will be recorded, any concomitant medications 
will be documented, all test article and subject diaries will be collected, and 
the subject will exit the study following a normal CST result.
Visit 4 (Day 15 ± 2 or EOS): Subjects will return to the clinic for the study 
staff to collect information on AEs, LSRs, concomitant medications, take 
blood and urine samples for clinical laboratory tests (chemistry, hematology, 
and urinalysis), draw a final trough PK blood sample prior (~12 hours 
following previous dose) to EOS CST, and perform the EOS CST. The EOS 
visit should be scheduled for the morning so that the EOS CST will occur at 
the same time (± one hour) as the CST performed at Visit 1 (Screening) and 
should, to the extent possible, be initiated between 7 and 9AM. If any of 
these subjects have adrenal suppression (defined as post-CST cortisol level 
< 18 μg/dL), they will be scheduled for one or more post-treatment follow-
up visits. Study staff will document IGA score, and percent BSA affected 
with disease in the Treatment Area and photographs (optional) will be taken. 
All female subjects will have a UPT. All test article and subject diaries will 
be collected. The subject will exit the study following a normal CST result.
Post-Treatment Follow-up Visits (Suppressed Subjects Only): Any subject 
who has evidence of adrenal suppression at EOS will return approximately 
every four weeks BUT no sooner than four weeks (28 days) after the EOS 
visit, and subsequently approximately every four weeks BUT no earlier than 
every four weeks (>28 days) thereafter for CST until the adrenal response 
returns to normal. Follow-up CST will be performed within ± 1 hour of 
Screening CST and should, to the extent possible, be initiated between 7 to 
9AM. It is important subjects remain off of all forms of steroid therapy 
(systemic, topical, injectable, etc.) during this post-treatment assessment 
period. See Section 9.3 for procedures to be performed at these post-
treatment follow-up visits.
Study Measurements
The following assessments will be performed per the schedule of events.
Investigator’s Global Assessment:
At Screening, Baseline Visit/Day 1, Day 8, and Day 15/EOS, the overall 
severity of the subject’s psoriasis in the Treatment Area will be evaluated
using the IGA score (5-point scale where 0 = clear, 1 = almost clear, 2 = 
mild, 3 = moderate, and 4 = severe). The IGA score is a static evaluation of 

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
Page 9 of 94 
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the overall or “average” degree of severity taking into account all of the 
subject’s psoriatic lesions in the Treatment Area (excluding those on the 
face, scalp, groin, axillae and other intertriginous areas) by the investigator 
or designee. This evaluation takes into consideration the three individual 
characteristics of psoriasis (plaque elevation, scaling, and erythema) with the 
IGA score at each visit representing the average of plaque elevation, scaling, 
or erythema that is present amongst all of the lesions eligible for treatment.
Percent Body Surface Area Affected with Disease:
The percent BSA affected with psoriasis in the Treatment Area (excluding 
the face, scalp, groin, axillae, and other intertriginous areas) will be 
estimated at the Screening Visit, Baseline Visit/Day 1, Day 8, and Day 15.
Percent Body Surface Area Treated with Test Article: 
The percent BSA treated with the test article will be estimated at Baseline 
Visit/Day 1 and Day 8 (for subjects who have not cleared). 
Test Article Compliance:
Subjects will apply the first dose of test article to all plaques within the 
Treatment Area under staff supervision. At each visit, subject diaries will be 
reviewed to determine test article doses taken since the last visit and subjects 
will be counseled regarding compliance if necessary. Subjects will be 
instructed to record the date that the last dose was applied. All dispensed 
canisters of test article will be weighed at each visit.  
Local Skin Reactions:
At each visit, subjects will be evaluated for the presence of any LSRs 
associated with the topical application of corticosteroids including 
telangiectasia, 
skin 
atrophy, 
burning/stinging, 
and 
folliculitis. 
Burning/stinging will be evaluated post-application at Baseline Visit/Day 1 
and Day 8 (for subject who have not cleared).
Adverse Events: 
All AEs will be recorded. At each visit after the Baseline Visit/Day 1, 
subjects will also be questioned specifically about the status of any ongoing 
AEs.
Clinical Laboratory Tests
Urine and blood samples will be collected from each subject for safety 
laboratory analysis at Visit 1/Screening, Visit 2/Baseline (if applicable), and 
Visit 4/EOS. Any new or worsening clinically significant abnormalities at 
Visit 4/EOS will be recorded as AEs.  
Cosyntropin Stimulation Test:
The EOS visit (i.e., the end of the assigned treatment period) should be 
scheduled in the morning so that the CST will occur at the same time (± one 
hour) as the CST performed at Visit 1 (Screening). The Screening CST will 
be initiated between 7 and 9AM; all follow-up CSTs should, to the extent 
possible, be initiated between 7 and 9AM.

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
Page 10 of 94 
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Pharmacokinetic Assessment:
Eligible subjects will have blood drawn at Screening for baseline drug 
concentration in plasma. On Day 8, all subjects, regardless of lesion 
clearance, will have blood drawn for assessment of trough drug 
concentration in plasma. At the Day 15 visit, subjects who have continued 
to treat lesions will have a final assessment of trough drug concentration in 
plasma approximately 12 hours (± 30 minutes) after their Day 14 evening 
application and just prior to the initiation of the CST.
Study Endpoints
HPA Axis Response to Cosyntropin - Measurement of serum cortisol 
concentrations after stimulation of the adrenal cortex with cosyntropin 
(Cortrosyn® tests). HPA axis suppression is defined as a post-stimulation 
serum cortisol level < 18 μg/dL assessed at the end of study. 
Plasma Levels of HBP - Trough HBP concentrations in plasma will be 
assessed at Screening, Day 8, and Day 15 approximately 12 hours (± 30 
minutes) post-treatment. 
Other Safety Endpoints - AEs, LSRs, clinical laboratory tests, UPTs, dosing 
compliance, and extent of exposure.
Sample Size 
Calculations
No formal power calculations were performed to establish the sample size.  
The number of subjects enrolled who complete the study is historically 
consistent with other HPA/PK studies.
Statistical Methods
All statistical analyses and summaries will be prepared using SAS® unless 
otherwise stated. All subjects enrolled in the study who were dispensed and 
applied test article at least once will be included in the analysis of safety and 
will be considered the Safety population. All enrolled subjects who applied 
at least one dose of test article and returned for at least one post-baseline visit
will be considered the modified intent-to-treat (mITT) population. Subjects 
discontinued from the study at Visit 2 due to ineligibility criteria (screen 
failures) will be excluded from the HPA axis suppression summaries. 
Subjects included in the PK analysis (PK population) must not have any 
significant protocol deviations and must have an 80% - 120% dose 
compliance based on number of applications. Clinical study sites should 
make every effort so that subjects do not miss consecutive doses.
Safety Analyses:
Dosing Compliance
Descriptive statistics will be used to summarize test article compliance. 
Measures of test article compliance will include the duration of treatment 
(number of days dosed), the total number of applications (determined from 
the actual number of applications reported by the subject), and the percent 
of expected doses applied. A subject will be considered compliant with the 
dosing regimen if the subject applies at least 80% but no more than 120% of 
the expected number of applications.
Extent of Exposure
The total amount of test article used (grams of test article applied) will be 
calculated from the weights of the returned test articles. Descriptive statistics 
(mean, median, standard deviation [SD], minimum and maximum) will be 

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
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determined for the total amount of test article used and average amount of 
test article used per application by each subject.
An approximation of the amount of test article applied per cm2 will be 
determined based on the average amount of test article used per application 
and an estimate of the percent BSA treated with the test article at 
Visit 2/Baseline. The BSA treated with test article (in square centimeters) 
will be determined from the Mosteller calculation [1]. 
Urine Pregnancy Tests
A listing of UPT results will be prepared.
Local Skin Reactions
The frequency distributions of the severities of LSRs associated with topical 
application of corticosteroids including telangiectasia, skin atrophy, 
burning/stinging, and folliculitis will be summarized at Baseline and all 
follow-up visits.  
Adverse Events
All subjects enrolled in the study who were dispensed and applied test article 
at least once will be included in the safety analyses (Safety population). All 
AEs reported during the study will be listed, documenting onset, whether 
therapy was required, any change in test article dosing, severity, possible 
relationship to test article, and outcome. Verbatim terms on the electronic 
case report forms (eCRFs) will be linked to preferred terms (PTs) and system 
organ class (SOC) using the Medical Dictionary for Regulatory Activities 
(MedDRA) mapping system. All reported AEs will be summarized by the 
number of subjects reporting AEs, SOC, PT, severity, and relationship to test 
article.
Clinical Laboratory Tests
Clinical laboratory tests will be evaluated for any clinically significant changes 
during the study period. All laboratory data (hematology, chemistry, and 
urinalysis) will be listed and reported in the units received by the laboratory. 
Shift tables by analyte and by out of range flag will be presented to facilitate 
the evaluation of change from Visit 1/Screening to Visit 4/EOS.
HPA Axis Suppression Analysis
HPA axis responses to CST will be dichotomized to normal and abnormal. 
An abnormal HPA axis response (HPA suppression) is defined as a 30-
minute post-stimulation serum cortisol level of <18 μg/dL at the end of 
study. The proportion of subjects manifesting laboratory evidence of adrenal 
suppression at the end of study will be summarized. The mean increases in 
serum cortisol levels after stimulation will also be summarized at the end of 
study. In addition, descriptive statistics for the daily dose of test article will 
be tabulated separately for suppressed and non-suppressed subjects. Post-
treatment follow up data will be summarized for subjects determined to have 
laboratory based evidence of adrenal suppression at the end of study or early 
termination visit.

Product Name: Halobetasol Propionate Foam, 0.05% 
Protocol: 122-0551-209 
Sponsor Name: Mayne Pharma LLC 
 
Protocol Date: April 12, 2019, v3.0 
CONFIDENTIAL
Page 12 of 94 
TI SOP 305-A Protocol Template, Version 06
Pharmacokinetic Analysis
Trough HBP concentrations in plasma on Day 8 and Day 15 will be 
calculated and summarized.