A Real-world Prospective Cohort Study of Patients With Moderate to Severe Acne Vulgaris Treated With Sarecycline (Seysara®) In Community Practice Settings in the U.S
Conditions: Acne Vulgaris
Sponsor: Almirall, S.A.

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Patient-reported Outcomes for Sarecycline 
Effectiveness and Safety (PROSES) 
 
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TABLE OF CONTENTS 
 
 
PAGE 
TABLE OF CONTENTS ............................................................................................................... I 
LIST OF ABBREVIATIONS ........................................................................................................ III 
PROTOCOL SUMMARY ............................................................................................................ V 
1 
KEY PERSONNELL AND CONTACT INFORMATION ....................................................... 1 
2 
INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ........ 2 
2.1 
Background Information .......................................................................................... 2 
2.2 
Rationale ................................................................................................................ 4 
3 
OBJECTIVES ..................................................................................................................... 4 
3.1 
Study Objectives ..................................................................................................... 4 
3.2 
Study End Points .................................................................................................... 5 
4 
STUDY DESIGN ................................................................................................................ 5 
5 
STUDY MEDICATION ........................................................................................................ 6 
6 
STUDY ENROLLMENT AND WITHDRAWAL .................................................................... 7 
6.1 
Subject Inclusion Criteria ........................................................................................ 7 
6.2 
Subject Exclusion Criteria ....................................................................................... 8 
6.3 
Strategies for Screening, Recruitment and Retention.............................................. 9 
6.3.1 
Site Investigators ......................................................................................... 9 
6.3.2 
Study Subjects ............................................................................................ 9 
6.4 
Subject Withdrawal ............................................................................................... 11 
6.4.1 
Reasons for Withdrawal ............................................................................ 11 
6.4.2 
Handling of Subject Withdrawals ............................................................... 11 
7 
STUDY SCHEDULE & PROCEDURES ........................................................................... 12 
7.1 
Enrollment/Baseline (Encounter # 1) ..................................................................... 12 
7.2 
Shipment of Study medication .............................................................................. 14 
7.3 
First Follow-up Encounter (Encounter # 2) ............................................................ 14 
7.4 
Second Follow-up Encounter (Encounter # 3) ....................................................... 15 
7.5 
Third Follow-up & Study Close-out Encounter (Encounter # 4) ............................. 16 
7.6 
Early Termination Encounter (Encounter # x) ....................................................... 18 
8 
STUDY ASSESSMENTS ................................................................................................. 18 
8.1 
PRO Assessments ................................................................................................ 18 
8.2 
Treatment Satisfaction Assessments .................................................................... 20 
8.3 
Treatment Effectiveness Assessments ................................................................. 20 
8.3.1 
Investigator Assessments.......................................................................... 20 
8.3.2 
Study Subject Assessments - Quantitative ................................................ 20 
8.3.3 
Study Subject Assessments - Qualitative .................................................. 21 
8.3.4 
Study Subject Photographic Assessments ................................................ 21 
8.4 
Additional Subject Assessments ........................................................................... 22 
8.5 
Compliance to Treatment ...................................................................................... 22 
8.6 
Safety Assessments ............................................................................................. 23 
8.6.1 
Definition of Adverse Events & Adverse Drug Reactions ........................... 23 
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8.6.2 
Documentation and Reporting of ADRs, Events with Fatal Outcome and 
Other Reportable Events ........................................................................... 24 
9 
STUDY OVERSIGHT ....................................................................................................... 26 
10 
SITE MONITORING, QUALITY CONTROL AND ASSURANCE ...................................... 26 
11 
DATA MANAGEMENT ..................................................................................................... 27 
12 
STATISTICAL CONSIDERATIONS .................................................................................. 28 
12.1 
Sample Size Considerations ................................................................................. 28 
12.2 
Analysis Populations and Datasets ....................................................................... 28 
12.3 
General Statistical Procedures .............................................................................. 29 
12.3.1 Overview ................................................................................................... 29 
12.3.1 Summary Statistics .................................................................................... 29 
12.3.2 Subgroup Analysis .................................................................................... 30 
12.3.3 Multivariate Analyses ................................................................................ 30 
12.4 
Primary Endpoint Analysis .................................................................................... 30 
12.5 
Secondary Endpoint Analysis ............................................................................... 31 
12.6 
Additional Analysis ................................................................................................ 32 
12.6.1 Treatment Satisfaction Analyses ............................................................... 32 
12.6.2 Treatment Compliance .............................................................................. 32 
12.6.3 Comparison of Investigator and Subject Assessment of AV Severity ........ 32 
12.6.4 CFB in PROs ............................................................................................. 33 
12.6.5 Comparison of Parent/Caregiver and Patient Perceptions of AV Severity 
and Impact ................................................................................................ 33 
12.6.6 Safety Assessments .................................................................................. 34 
12.7 
Missing Data Handling .......................................................................................... 34 
12.8 
Sensitivity Analyses .............................................................................................. 35 
13 
SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS .................. 35 
14 
ETHICS/PROTECTION OF HUMAN SUBJECTS ............................................................. 36 
14.1 
Ethical Standard ................................................................................................... 36 
14.2 
Institutional Review Board .................................................................................... 36 
14.3 
Informed Consent Process ................................................................................... 37 
14.4 
Participant Confidentiality ..................................................................................... 37 
15 
OTHER INFORMATION ................................................................................................... 38 
15.1 
Publication and Disclosure Policy ......................................................................... 38 
15.2 
Termination of the Study ....................................................................................... 38 
16 
LITERATURE REFERENCES .......................................................................................... 39 
17 
APPENDICES .................................................................................................................. 41 
17.1 
APPENDIX A: Study Schedule of Events .............................................................. 42 
17.2 
Appendix B: Select Study Questionnaires ............................................................. 43 
17.3 
APPENDIX-C: Signature Page ............................................................................. 47 
 
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LIST OF ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event/Adverse Experience 
App 
Application / Mobile Application 
Approx. 
Approximately 
ASIS 
Acne Symptom and Impact Scale 
AV 
Acne Vulgaris 
CASRO 
Council of American Survey Research Organizations 
CFB 
Change From Baseline 
CIRQ 
The CASRO Institute for Research Quality 
ClinRO 
Clinician Reported Outcome 
CRO 
Clinical Research Organization 
DCF 
Data Collection Form 
EC 
Ethics Committee 
EDC 
Electronic Data Collection 
EU 
European Union 
eDCF 
Electronic Data Collection Form 
FAS 
Full Analysis Set 
FDA 
The U.S Food and Drug Administration 
GEP 
Good Epidemiology Practices 
HCP 
Healthcare Provider 
HRQoL 
Health Related Quality of Life 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IGA 
Investigator’s Global Assessment 
IRB 
Institutional/Independent Review Board 
Med 
Medication 
N 
Number (typically refers to participants) 
PI 
Principal Investigator 
PRO 
Patient Reported Outcome 
PROMS 
Patient Reported Outcome Measures 
PtGA 
Patient Global Assessment 
QoL 
Quality of Life 
Qr 
Questionnaire 
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RCT 
Randomized Controlled Trial 
RWE 
Real World Evidence 
SAE 
Serious Adverse Event  
SAP 
Statistical analysis plan 
SD 
Standard Deviation 
SEM 
Standard Error of Mean 
SOP 
Standard Operating Procedure 
TBD 
To Be Decided 
US 
United States 
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PROTOCOL SUMMARY 
Title: 
Patient-reported Outcomes for Sarecycline Effectiveness and 
Safety (PROSES). 
Précis: 
A prospective cohort study of patients with acne vulgaris (AV) 
treated with sarecycline and followed for 12 weeks post 
treatment-initiation. Patient Reported Outcomes (PROs) and 
clinical profile of patients will be gathered for descriptive 
analyses of patient outcomes over the 12 week study 
observation period. 
Objectives: 
Evaluate PROs and clinician reported outcomes among 
patients with moderate to severe non-nodular AV who are 
prescribed sarecycline in clinical practice settings in the U.S. 
 
Primary:  Evaluate PROs related to Acne symptoms and 
impact. 
 
Secondary: Evaluate sarecycline treatment effectiveness, in 
terms of IGA of AV severity on the face. 
Additional: Evaluate clinician satisfaction with sarecycline 
treatment, sarecycline safety/tolerability, and concordance in 
perception of facial AV severity among clinicians and patients. 
Population: 
Three hundred (300) patients of age >9 years at the time of 
initiation of treatment with sarecycline from clinical practices 
across the U.S. For pediatric patients, their parents/primary 
caregivers will also be recruited. 
Number of Sites: 
Maximum of fifty sites will be recruited. 
Duration of 
Treatment 
12 weeks. 
Study Drug & 
Mode of 
Administration 
Seysara® tablets; 60 mg, 100 mg, 150 mg, providing a dose of 
approx. 1.5mg/kg/day; oral. Commercial supply of medication 
may be supplied to clinical sites/Subjects for the duration of the 
study. 
Study Duration: 
Approximately eighteen months of study duration, including 
study set-up, 12 weeks of subject observation period and study 
close out followed by study data analyses. 
 
 
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Schematic of Study Design 
 
Subject 
Screening 
 
 
 
 
Encounter 
# 1 
 
 
 
Encounter 
# 2 
 
 
 
 
Encounter 
# 3 
 
 
 
 
Encounter 
# 4 
 
 
 
 
 
 
 
*Subject screening could be done via phone, prior to Subject’s visit to the clinic; or it could be combined 
with Encounter # 1 (baseline data collection). 
Clinicians shall prescribe sarecycline (Seysara®) to eligible Subjects per own clinical judgement and 
manage them as they normally would, in clinical practice.
Final descriptive 
study data analyses 
8-week follow-up assessment with Subjects and Site Investigators 
(encompasses select PROs, AV severity, & adverse events) 
Screen* potential study participants. 
Confirm Subject eligibility, Obtain Informed Consent/Assent. 
Baseline data collection from Subjects & Site Investigators  
(encompasses demographics, clinical characteristics, concomitant meds, PROs, 
perceptions, satisfaction, AV severity & adverse events) 
4-week follow-up assessment with Subjects and Site Investigators 
(encompasses select PROs, AV severity, & adverse events) 
 
12-week follow-up assessment with Subjects and Site Investigators 
(encompasses PROs, perceptions, AV severity, concomitant meds & adverse 
events) 
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1 KEY PERSONNELL AND CONTACT INFORMATION 
 
Principal 
Investigators:   
 MD 
Ph 
 
 
 
 MD, MBA  
Ph 
 
    
 
Other Key 
Personnel 
 MS, MHS, MPhil (PhD) 
Ph 
 
 
 
 MD, MHA 
Ph 
 
 
 
 PhD 
Ph 
 
 
 
MD 
Ph 
 
 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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2 INTRODUCTION:  BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
2.1 
Background Information 
Acne Vulgaris (AV), hereinafter referred to as acne, affects up to 50 million Americans and is 
the most common skin condition in the United States (US) (Bickers et al, 2006). Acne affects 
both adolescents and young adults. Approximately 85 percent of people between the ages of 12 
and 24 experience at least minor acne (Bhate & Williams, 2013). Since patients may have acne 
over a long duration of time, and may also experience recurrence and relapse, and manifestations 
such as acute outbreaks or slow onset, acne may be classified as a chronic disease (Cherynshov 
et al, 2018).  
Core outcomes in acne studies often focus on clinical assessment of acne severity, in terms of 
investigator global assessment (IGA) or lesion counts. Patient reported outcome measures 
(PROMs) have been sporadically used, but the increased recognition of their importance to 
patients has resulted in a proliferation of studies depicting the impact of acne on patient’s health-
related QoL (HRQoL) (Thiboutot et al, 2019). Acne has been shown to negatively affect QoL 
resulting in low self-esteem, increased social and emotional anxiety (Timms, 2013; Revol et al, 
2015). Patients with acne report more effects of their skin condition on their functioning, 
emotions, and symptoms than do patients with isolated benign skin lesions or those in the 
normative sample (Lasek & Chren, 1998). Acne has been associated with considerable 
psychosocial impact, causing significant negative effects on self‐image leading to feelings of 
isolation and loneliness, and a significantly lower self‐attitude, uselessness feeling, sense of pride 
and self‐worth, and body satisfaction (Gieler, 2015). 
Several QoL instruments have been used in acne studies, with varying level of focus on patient 
attributes impacted by acne (Alexis et al, 2014; Cherynshov et al, 2018). An expert panel of 
dermatologists was recently convened (in December 2020) to review the existing QoL 
instruments and identify key patient-centric elements that reflects the day-to-day concerns of 
their adult and pediatric acne patients. An existing 17-item validated instrument, namely, Acne 
Symptom and Impact Scale (ASIS) that asks patients about the acne signs and impact of acne on 
emotional and social wellbeing, was used as the anchor for further panel deliberations on 
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complimentary PROMs. Using a qualitative modified delphi method, the expert panel agreed on 
10 specific items that relate to how acne impacts the patient’s mood (anger/sadness), social 
interactions, general thoughts/worries about acne and one’s future goals, and impact on daily 
activities, including sleep. These recommendations are aligned with research on factors 
impacting young acne patients (Seite et al, 2012; Timms, 2013; Lafrance & Carey, 2018). The 
panel also suggested comparing the perceptions of acne severity of patients with those of their 
treating clinicians, and the perceptions of pediatric patients with those of their parents; and 
suggested the utility of comparing the parent/caregiver perceptions of acne severity and impact 
to that of their children. The 10 main patient-centric questions constituting the Expert Panel 
Questionnaire along with ASIS questionnaire was identified as an optimal tool to use in 
community-based real world research involving acne patients. 
Besides QoL, fear/concerns of side effects to existing treatments are in the minds of acne patients 
(Tuchayi, 2016). Newer treatments, such as sarecycline (Seysara®), an oral tetracycline class 
narrow-spectrum antibiotic indicated as first line therapy for the treatment of moderate to severe 
AV, may be viable options to acne patients, owing to the proven safety profile, in addition to the 
efficacy (Moore et al, 2018; Deeks, 2019). As antibiotic resistance remains a concern for 
clinicians and patients alike (Kircik, 2010; Farrah & Tan, 2016; Del Rosso et al, 2019), the 
narrow-spectrum antibiotic attribute of sarecycline with a lower propensity for antibiotic 
resistance may be appealing to these stakeholders (Zhanel et al, 2019). 
In two pivotal RCTs, after 12 weeks of treatment, statistically significantly more recipients of 
once-daily sarecycline 1.5 mg/kg (as tablets) than of placebo achieved treatment success on the 
face; for those affected, acne on the chest and back also improved statistically significantly with 
sarecycline (Moore et al, 2018; Deeks, 2019). Sarecycline was generally well tolerated; other 
broad-spectrum tetracycline-class antibiotics are often associated with certain gastrointestinal, 
vestibular and phototoxic adverse effects and, in females, vaginal yeast infections, although these 
treatment-emergent adverse events were generally uncommon with sarecycline. As importantly, 
sarecycline was associated with HRQoL benefits, depicted by more favorable outcomes 
measured using Skindex-16 questionnaire (Moore et al, 2018; Deeks, 2019).  
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The clinical trial results of sarecycline highlight the clinical and QoL benefits derived by the 
acne patients. The demonstration of sarecycline-related benefits, including its impact on patient 
HRQoL in real world community practice settings is warranted to highlight sarecycline value 
proposition to patients, clinicians and payers alike. The ASIS questionnaire, along with the 
complimentary novel Expert Panel Questionnaire on patient HRQoL could be beneficial to use 
for research in community practice settings. 
 
2.2 
Rationale 
General understanding of acne impact on different aspects of patient HRQoL is still evolving. A 
real-world study leveraging validated HRQoL instruments such as ASIS questionnaire and the 
complimentary novel Expert Panel Questionnaire (developed using modified delphi method) 
could help portray a broader picture of impact of acne on pediatric and adult patient HRQoL. 
Further, assessing the impact of sarecycline treatment on acne patient outcomes, including 
patient HRQoL, in real-world community practice settings could highlight the humanistic and 
clinical benefits associated this narrow-spectrum antibiotic treatment option. 
 
3 OBJECTIVES 
3.1 
Study Objectives 
The primary objective of the study is to evaluate PROs in terms of health related quality of life 
(HRQoL) among patients with moderate to severe non-nodular AV who are administered 
sarecycline in real-world community practice settings in the U.S. The secondary objective is to 
evaluate effectiveness of sarecycline treatment, measured by Investigator Global Assessment 
(IGA) of AV severity on the face.  
 
The additional study objectives include the following evaluations among study Subjects and Site 
Investigators*: 
• Investigator satisfaction with their sarecycline treatment outcomes. 
• Safety and tolerability of sarecycline. 
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• Comparison of Investigator and Subject perceptions of AV severity. 
 
Note: Dermatologists are expected to predominantly constitute the Site Investigator category, while a few physician 
assistants and nurse practitioners may be included in the study, reflecting the routine care management of acne in 
community practice settings. 
 
3.2 
Study End Points 
The primary endpoint of the study will be the PROs, in terms of self-perceived acne symptoms 
and impact of acne on emotional functioning, social functioning and activities of daily living, at 
Week 12. 
The secondary endpoint will be the proportion of Subjects with Facial IGA success at Week 12, 
defined as a 2-point decrease in IGA score from baseline and a score of 0 (clear) or 1 (almost 
clear). 
 
Additional endpoints of the study will include: 
• Proportion of Subjects for whom Site Investigator reported ‘very satisfied’ or ‘satisfied’ 
in the question on global satisfaction with sarecycline treatment, at Week 12. 
• Description of changes in PROs from baseline, at Week 12. 
• Frequency of documented adverse events (AEs) and severe adverse events (SAEs) during 
the 12-week study observation period. 
• Comparison of Subject perception and Site Investigator perception of AV severity, at 
Week 12. 
 
4 STUDY DESIGN 
 
This is a single-arm, prospective cohort study which will enroll patients with moderate to severe 
acne vulgaris (AV) who are prescribed sarecycline in real-world community practices in the U.S. 
Caregivers will also enroll in the study, in case of pediatric patients. Study Subjects will be 
followed for up to 12 weeks post-index date (with the ‘index-date’ defined as the date of initiation 
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of sarecycline). Study Site Investigators and Subjects will complete online surveys at baseline (at 
time of study enrollment) and at weeks 4, 8 and 12, post-index date. 
 
This study will entail provision of sarecycline treatment to study participants. Site Investigators 
will decide on who to prescribe sarecycline as part of usual care, based on their best clinical 
judgment, prior to subject recruitment. The study is sponsored by Almirall, hereinafter referred to 
as the Sponsor. The study will be managed by Avant Health, hereinafter referred to as the Contract 
Research Organization (CRO).  
 
5 STUDY MEDICATION 
 
The study protocol will require identification and selection of patients considered as candidates 
for a specific medication, namely, sarecycline (Seysara®), as part of usual care. In this context, 
the study medication will be sarecycline (Seysara®). Site Investigators shall provide the 
commercial supply of sarecycline (Seysara®) to eligible study Subjects. 
 
Sarecycline has a restricted market access in the U.S, with payers reimbursing for the commercial 
prescriptions on a restricted basis. Selection of only the patients who are able to fill the prescription 
for reimbursed sarecycline may not be representative of individuals who might be candidates for 
sarecycline in the U.S; this may impact the generalization of the study results. To avoid this 
potential selection bias and improve the prospect of generalization of study results, the commercial 
supply of sarecycline (Seysara®) will be supplied to Site Investigators for the study duration of 12 
weeks. 
 
Per FDA prescribing information, the recommended dosage of sarecycline is once daily with or 
without food: 
• 
60 mg for patients who weigh 33-54 kg,  
• 
100 mg for patients who weigh 55-84 kg, 
• 
150 mg for patients who weigh 85-136 kg. approximately 1.5 mg/kg once daily 
 
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The Site Investigators will prescribe relevant sarecycline dose to patients per their clinical 
judgement. Correspondingly, sarecycline prescribed dose at the start of the study and any 
subsequent modifications to dose during the study observation period will be captured as part of 
study data collection. 
6 STUDY ENROLLMENT AND WITHDRAWAL 
 
A total of three hundred (300) Subjects will be enrolled in the study, from a maximum of fifty (50) 
community practices (sites) from across the U.S. During the study enrollment window, study-
eligible clinical sites will be sequentially screened, consented for study participation and 
completion of all study procedures, including enrollment of study eligible Subjects. 
 
The study Subjects will be patients with moderate to severe non-nodular AV who are candidates 
for sarecycline, and caregivers of pediatric patients (age <18 yrs) within this cohort. The study 
cohort will be drawn from dermatology clinics from across the U.S. 
 
6.1 
Subject Inclusion Criteria 
Patient Inclusion Criteria: In order to be eligible to participate in this study, an individual must 
meet all of the following criteria: 
• Male or female, aged 9 years and above at the time of study recruitment. 
• Has facial non-nodular AV with IGA score of moderate (3) or severe (4). 
• Considered as a potential candidate for sarecycline treatment to manage their AV, per 
clinician’s judgment. 
• Able to read and write English. 
• Provide consent (in case of adult patients) or assent (in case of pediatric patients) to 
participate in the study. 
• Willing to comply with all study procedures and be available for the duration of the study. 
 
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Caregiver Inclusion Criteria: In order to be eligible to participate in this study, an individual must 
meet all of the following criteria: 
• Male or female, aged 18 years and above. 
• Able to read and write English. 
• Primary caregiver of the study-eligible patient. 
• Provide consent to participate in the study. 
• Willing to comply with all study procedures and be available for the duration of the 
study. 
 
6.2 
Subject Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation in this 
study: 
• Patients with any dermatological or physical condition of the face that could interfere with 
the AV clinical evaluations. 
• Patients with any history of allergy to tetracycline-class antibiotics, pseudomembranous 
colitis or antibiotic-associated colitis. 
• Patients with any known resistance to other tetracyclines. 
• Patients currently treated with any of the following: penicillin, oral retinoids (incl. 
Isotretinoin and acitretin). 
• Among female Subjects: Currently pregnant, lactating, or is planning a pregnancy during the 
study period. 
• Patients or their caregivers are unable to comply with the requirements of the study or 
patients who in the opinion of the Site Investigator should not participate in the study. 
• Patients for whom medical chart is inaccessible to Site Investigators to complete baseline 
data collection. 
 
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6.3 
Strategies for Screening, Recruitment and Retention 
6.3.1 
Site Investigators 
Screening of potential study sites/investigators will take place by reaching out directly to sites and 
sharing study synopsis and soliciting their interest. If a site expresses interest in the study, they 
will be asked to consent for study participation. Subsequently, additional information will be 
shared for contracting and site initiation for subject screening. 
 
All Site Investigators will be nominally compensated (per fair market value) for the study activities 
they undertake, encompassing subject screening/recruitment, data collection using online 
electronic data collection forms (eDCFs) at baseline (at time of enrollment), and at weeks 4, 8 and 
12 post-index date. Periodic follow-up with the study sites will take place throughout the study 
observation period to ensure engagement and retention. 
6.3.2 
Study Subjects 
Upon successful recruitment of the study sites, the respective Site Investigators may identify a 
study coordinator at their clinics. Site Investigators and/or the study coordinator will approach, 
screen and consent up to ten (10) study-eligible Subjects sequentially within the study enrollment 
window. The approach may take place during the routine patient visit or via email or phone; upon 
establishing contact with study Subjects, they will be provided with a description of study 
objectives and procedures.  
 
In the case of in-person recruitment of study Subjects, Subjects will be screened for study 
eligibility using the study screener. The Subjects deemed eligible for the study will then be 
provided with a study informed consent form. The study coordinator or Site Investigator will 
ensure that Subjects can read the consent form and ask questions, and be given adequate time to 
consider the benefits/risks associated with participation in the study. An informed consent (with 
an accompanying assent, if applicable, for pediatric patients) will be obtained from each subject 
(and parent(s) or legal guardian(s), if applicable) in accordance with applicable regulations prior 
to participating in any study procedures. Subjects under the age of 18 will assent.  
 
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In the case of recruitment of study Subjects via email or phone, study coordinator or Site 
Investigator will pre-screen the Subjects for study eligibility, and will then contact the subject to 
describe the study to each subject (and parent(s) or legal guardian(s), if applicable) and give them 
adequate time to consider the risks associated with participation in the study. The eligible Subjects 
will be then provided with a weblink to an online screener and electronic consent (e-consent) form. 
If a Mobile App is used for the purpose of the study data collection from the Subjects, recruited 
study Subjects will be asked to download the Mobile App; as they log-in an e-consent form may 
be presented via the App. Subjects will be able to quickly read and provide informed consent (and 
assent if applicable, for pediatric patients) prior to participating in any study procedures by 
checking a box next to the statement, “I have read the above statement and I consent to participate 
in this study” and signing their name(s) along with dating the online form (using their web browser 
or the study Mobile App). 
 
Site Investigator or the study coordinator will assign subject IDs to Subjects sequentially, as they 
are recruited. Site coordinator will maintain a recruitment log that will identify the subject ID 
number to their name/contact info. For study follow-up reminders, the study subject will be 
consented to share their contact details with study research staff; such information will be kept 
strictly confidential and not shared with the study sponsor, and this administrative information will 
not be part of the research study data thereby preserving the anonymity of study Subjects. 
 
Only positively-screened and consenting patients will be allowed to participate in the study and 
proceed with the study steps. Study subjects will be compensated nominally (per fair market value) 
for survey completion at baseline (at recruitment) and at weeks 4, 8 and 12 post-index date. Study 
coordinators and/or their Site Investigators will serve as the main point of contact for 
participants/Subjects at their site for questions and ensure subject retention during the study 
observation period. Reminders for eDCF completion may be sent to study Subjects via email, 
phone or via the Mobile App. 
 
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6.4 
Subject Withdrawal 
This is a real-world study and the study participation is completely voluntary. Subjects may 
withdraw voluntarily from the study at any juncture during the study observation period 
following the enrollment, for any reason.  
Site Investigator may terminate a subject’s participation in the study at any juncture, in specific 
scenarios, as outlined below. 
6.4.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request.  
A Site Investigator may terminate a study subject’s participation in the study if: 
• Any medical condition, event or situation occurs such that continued participation in the 
study would not be in the best interest of the subject. This may include pregnancy among 
female subjects. 
• In the event Subjects are unable to swallow the sarecycline tablets after enrollment, they will 
be discontinued from the study and the reason for study discontinuation will be recorded as 
the inability to swallow tablet. 
• The subject meets a study exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation. 
   
6.4.2 
Handling of Subject Withdrawals 
If a subject requests withdrawal from the study voluntarily for any reason, the Site Investigators 
or site coordinator will follow-up with the patient to solicit and document the reason for 
withdrawal. If the Site Investigator determines that the withdrawal is related to a severe adverse 
event (SAE) associated with sarecycline, he/she will gather necessary information concerning the 
SAE. The Site Investigator may follow-up with the subject subsequently to ensure resolution of 
SAE episode and close out the study documentation for the concerned Subject. 
There will be no replacement of Subjects who withdraw or discontinue early from the study. 
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7 STUDY SCHEDULE & PROCEDURES 
Study eligible patients who are considered as candidates for sarecycline treatment as part of 
usual care Acne management will be screened, consented and recruited into the study, followed 
for up to 12 weeks post-index date, encompassing four distinct data collection encounters. With 
‘T’ being the index date of sarecycline treatment initiation, the baseline data collection may 
transpire anytime between T= -2 weeks post-index date and T= +4 days post-index date; the 4-
week follow-up data collection will happen at T=4 weeks post-index date + 4 days; the 8-week 
follow-up data collection will happen at T=8 weeks post-index date + 4 days, and 12-week 
follow-up data collection will happen at T=12 weeks post-index date + 4 days. Index date is the 
date of initiation of sarecycline treatment, when the subject took the first sarecycline dose. 
Different data elements will be collected from Site Investigators and from study Subjects at these 
data collection encounters, as outlined below. For patients of age 12yrs and older, acne patients 
themselves will complete relevant PRO elements pertinent to study endpoints, at all encounters; 
for patients of age 9-11yrs, parents/caregivers of pediatric patients will complete the PRO 
elements at all encounters, serving as a proxy, upon consulting with their child on question 
responses. 
The schedule of events is summarized in Appendix A. 
 
7.1 
Enrollment/Baseline (Encounter # 1) 
Baseline data collection will take place at the time of subject enrollment into the study or within 
a few days of recruitment. The subject encounters are expected to take place during in-person 
subject visits to the clinic, but remote/virtual visits will be allowed where Covid-related 
protocols prevent in-person visits. The recruited Site Investigators and study Subjects will be 
sent a weblink to the eDCFs and survey respectively for their completion. Subjects will be able 
to access the surveys on their mobile phone, using a study-specific Mobile App. 
The following data elements will be collected at baseline, from patient medical charts and/or per 
Site Investigator’s best clinical judgement based on their recent encounter with the study subject 
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while prescribing sarecycline as part of usual care and based on subject’s recent past medical 
history: 
• Demographics (e.g., age, gender). 
• General clinical characteristics, as documented in medical charts (incl. blood pressure, 
waist circumference, height/weight measurements, comorbidities). 
• AV disease characteristics (AV history; current IGA of AV severity in face). 
• Past AV treatment history (used ever, and those used within the past 6 months). 
• Sarecycline treatment characteristics (dose, frequency, date of recommendation). 
• Concomitant medications (for AV and comorbidities). 
• Perceptions about antibiotics/antibiotic resistance.  
The following data elements will be collected at baseline, from study Subjects, via online survey 
portal or a mobile app: 
• Demographics (e.g., gender, race/ethnicity, education, employment/school status, living 
status). 
• Perceptions of AV-related symptoms and impact of AV on emotional functioning, social 
functioning and activities of daily living. 
• Perceptions about antibiotics/antibiotic resistance (asked in only Adult Subjects). 
In case of pediatric patients, Caregivers will also complete a battery of questions related to their 
own perceptions of antibiotics/antibiotic resistance, their child’s current acne severity, and 
impact of acne on their child. 
In a small subset of sites, Site Investigators may utilize Canfield® photography equipment to 
take photographs of patient’s face to document the baseline AV severity of acne patients in the 
study, during in-person patient visits. 
 
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7.2 
Shipment of Study medication 
Following the Site Investigator’s decision to prescribe sarecycline (Seysara®) to study eligible 
patients, a commercial supply of the appropriate dose and quantity of study medication will be 
shipped to the attention of Site Investigator at their clinic/site. The study Subjects will be asked 
to record the first day of administration of sarecycline via the mobile app, and this date will 
constitute the study ‘index date’, upon which the follow-up encounter timepoints (at weeks 4, 8 
& 12) will be determined. 
7.3 
First Follow-up Encounter (Encounter # 2) 
At the completion of 4 weeks (+ 4 days) post-index date, the Site Investigator and Subjects will 
be asked to complete the first follow-up data collection, conducted via in-person or 
virtual/remote visits. 
The patients will be advised to visit their site/clinician’s offices to do the following: 
• Drop off the first tablet/pill bottle of Seysara® (bottle # 1) supplied to them at study start, 
be it empty or with left-over pills. 
o This may be done as curb-side interaction, without entering clinician’s offices. 
• Pick-up the second bottle of Seysara® supply (bottle # 2) for the next four weeks of use. 
o This may be done as curb-side interaction, without entering clinician’s offices. 
• Undergo AV clinical evaluation inside clinician’s office, if feasible. 
 
The Site Investigators will complete the following, based on the information documented in 
patient medical charts and per clinical judgment guided by observing study subject via in-person 
or virtual/remote visit: 
• IGA of current AV severity on the face. 
• Patient treatment compliance, per sarecycline pill/tablets left over in the subject-returned 
bottle. 
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• Modifications to sarecycline treatment characteristics (e.g,, change in dose, 
discontinuation), in the past 4 weeks, if any. 
• AEs (incl. SAEs) related to or possibly related to sarecycline, observed in the past 4 
weeks, as documented in the medical charts. 
• Information on withdrawal from study (if occurred within the past 4 weeks). 
 
The study Subjects will provide the following information via online survey portal or a mobile 
app: perceptions of current AV-related signs/severity. In case of pediatric patients, this 
information will be obtained from parents/caregivers as well. 
 
7.4 
Second Follow-up Encounter (Encounter # 3) 
At the completion of 8 weeks (+ 4 days) post-index date, the Site Investigators and Subjects will 
be asked to complete the second follow-up data collection, conducted via in-person or 
virtual/remote visits. 
The patients will be advised to visit their site/clinician’s offices to do the following: 
• Drop off the second tablet/pill bottle of Seysara® (bottle # 2) supplied to them at the Wk-
4 visit, be it empty or with left-over pills. 
o This may be done as curb-side interaction, without entering clinician’s offices. 
• Pick-up the third bottle of Seysara® supply (bottle # 3) for the next four weeks of use. 
o This may be done as curb-side interaction, without entering clinician’s offices. 
• Undergo AV clinical evaluation inside clinician’s office, if feasible. 
 
The Site Investigator will complete the following, based on the information documented in 
patient medical charts and per clinical judgment guided by observing study subject via in-person 
or virtual/remote visit: 
• IGA of current AV severity on the face. 
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• Patient treatment compliance, per sarecycline pill/tablets left over in the subject-returned 
bottle. 
• Modifications to sarecycline treatment characteristics (e.g,, change in dose, 
discontinuation), in the past 4 weeks, if any. 
• AEs (incl. SAEs) related to or possibly related to sarecycline, observed in the past 4 
weeks, as documented in the medical charts. 
• Information on withdrawal from study (if occurred within the past 4 weeks). 
 
The study Subjects will provide the following information via online survey portal or a mobile 
app: perceptions of current AV-related signs/severity. In case of pediatric patients, this 
information will be obtained from parents/caregivers as well. 
 
7.5 
Third Follow-up & Study Close-out Encounter (Encounter # 4) 
At the completion of 12 weeks (+ 4 days) post-index date, the Site Investigators and Subjects 
will be asked to complete the third and final follow-up data collection to close out the study. The 
subject encounters are expected to take place during in-person subject visits to the clinic, but 
remote/virtual visits will be allowed where Covid-related protocols prevent in-person visits. 
Subjects will be asked to drop off the third tablet/pill bottle of Seysara® (bottle # 3) supplied to 
them at the Wk-8 visit, be it empty or with left-over pills. 
 
The Site Investigators will complete the following, based on the information documented in the 
corresponding patient medical charts and per clinical judgment guided by observing study 
subject via in-person or remote/virtual visit: 
• Current IGA of current AV severity on the face. 
• Patient treatment compliance, per sarecycline pill/tablets left over in the subject-returned 
bottle. 
• Modifications to sarecycline treatment characteristics (e.g,, change in dose, discontinuation), 
in the past 4 weeks, if any. 
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• Perceptions of sarecycline overall treatment satisfaction. 
• AEs (incl. SAEs) related to or possibly related to sarecycline, observed in the past 4 weeks, 
as documented in the medical charts. 
• Information on withdrawal from study (if occurred within the past 4 weeks). 
• Newly documented changes to patient clinical characteristics, as documented in medical 
charts in past 12 weeks since the baseline encounter (incl. blood pressure, weight, 
comorbidities). 
• Modifications made to concomitant medications (for AV and comorbidities) in the past 12 
weeks since the baseline encounter.  
 
In the instances when in-person subject visits take place at Week 12, for those patients for whom 
baseline photographic data collection was completed, corresponding Site Investigators will take 
photographs of patient’s face to document current acne severity at Week 12. 
 
The study Subjects will provide the following information via online survey portal or a mobile 
app: Perceptions of AV-related symptoms and impact of AV on emotional functioning, social 
functioning and activities of daily living. In a small subset of sites, clinicians will request 
Subjects to provide a 1–3 minute audio recording of Subject’s perception of sarecycline 
treatment benefits experienced during the study period. 
In case of pediatric patients, Caregivers will also complete a battery of questions related to their 
perceptions of child’s current acne severity, and impact of acne on their child. 
Both the Site Investigators and Subjects will be thanked for their participation in the study. No 
specific study close-out tasks are expected of the study Subjects. Site Investigators will be asked 
to submit any outstanding data queries to the research team and then close out the study records 
at their respective sites. 
 
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7.6 
Early Termination Encounter (Encounter # x) 
Site Investigators will attempt to follow the progress of every subject admitted to the study 
through to study completion.  If a subject fails to complete requested study procedures (i.e, 
completion of online surveys), a reasonable effort will be made to contact the subject and 
ascertain the reason(s) for non-compliance with study procedures.  
If a subject does not complete the study for any reason (including Investigator discretion), the 
reason and circumstances for the subject’s early termination will be fully documented; if 
possible, the assessments specified for the forthcoming (next) study encounter will be performed.  
 
8 STUDY ASSESSMENTS 
PROs will be assessed with study Subjects. Sarecycline treatment effectiveness will be assessed 
by treating Site Investigator using IGA scores and lesion counts. Safety will be evaluated in 
terms of adverse events and ADRs during the treatment period. 
 
8.1 
PRO Assessments  
A combination of a validated questionnaire and an ad hoc questionnaire prepared via modified 
delphi panel consensus method involving dermatologists, will be used for PRO assessments. 
ASIS Questionnaire: 
The ASIS is a 17-item questionnaire that asks patients about the signs and impact of AV 
(Appendix B); responses are reported as two scales: Signs (9 items), and Impact (8 items). 
Impact domain has two subscales, pertinent to Emotional (6 items) and Social impact (2 items). 
The following questions (items) correspond to each scale:  
 
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Scale 
Items 
Signs 
1-9 
Impact 
10-17 
 
All items are scored on a five-point adjectival response scale, with a potential score of 0 to 4, 
even though the individual item responses are different for certain question clusters. A domain 
score is determined by the average of scores in each scale within the domain. A total score is the 
average of all 17 items. Higher scores on the ASIS Sign domain, comprised of all items that 
assess symptoms (items 1-9), indicate the presence of more severe symptoms, whereas higher 
scores on the ASIS Impact domain, comprised of all of the items that assess impacts (items 10-
17), indicate a greater negative impact of acne on HRQoL and appearance. The questionnaire 
will be administered in entirety, at baseline and at Week 12 post-index date. 
 At Weeks 4 & 8 post-index date, Subjects will be asked to complete ASIS Item # 9 (how is your 
acne on your face right now) and ASIS Item # 10 (rate how your face looked because of your 
acne). 
Expert Panel Questionnaire: 
Ten (10) ad hoc questions related to patient perception of impact of Acne on their social 
functioning, emotional functioning and activities of daily living were formulated based on an 
expert consensus involving a panel of dermatologists using modified delphi method. The items 
relate to how Acne impact patient’s mood (anger), social interactions, general thoughts/worries 
about Acne and one’s future goals, and impact on daily activities, including sleep (Appendix B). 
All items are scored on a five-point adjectival response scale, with a potential score of 0 to 4, 
even though the individual item responses are different for certain question clusters. The 
questions will be administered in entirety, at baseline and at Week 12 post-index date. 
 
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8.2 
Treatment Satisfaction Assessments 
Investigator’s global satisfaction with sarecycline treatment will be assessed at Week 12 using a 
single question: “how satisfied are you with sarecycline treatment outcomes”, with response 
options ranging from ‘Very Satisfied’ to ‘Very Dissatisfied’.  
8.3 
Treatment Effectiveness Assessments 
The effectiveness of sarecycline treatment will be assessed from the perspective of Site 
Investigators as well the Subjects. 
8.3.1 
Investigator Assessments 
An IGA scale of 0 (Clear) to 4 (Severe) will be used by the Site Investigators to assess the 
severity of a subject’s facial acne at the time of study encounters. The IGA should be 
representative of the investigator’s overall general assessment of the subject’s Acne and take into 
account the quality, as well as the quantity, of lesions. These assessments will be done at 
baseline encounter to document AV severity before initiation of sarecycline treatment; the 
assessments will be repeated by the Site Investigators at study subject follow-up encounters at 
Weeks 4, 8 & 12, post-index date. The comparison of follow-up assessments to the baseline 
assessment will help determine treatment effectiveness. It is expected that the Investigator 
assessments will be conducted via in-person visits/encounters at baseline and week-12, and when 
in-person assessments are not feasible (owing to COVID-related travel restrictions), the 
assessments maybe done via virtual/remote visits. The same evaluator shall perform all 
evaluations for a subject during the study, as feasible. 
8.3.2 
Study Subject Assessments - Quantitative 
The study Subjects will undertake multiple assessments to report their self-perceived severity of 
AV in general. These assessments will be done at baseline encounter to document the perception 
of AV severity corresponding to the time of initiation of sarecycline. They are then repeated by 
the Subjects at ensuing encounters at Weeks 4, 8 & 12, post-index date. 
 
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Patient Global Assessment (PtGA) 
This is based on the global acne severity question within ASIS (Item # 9), where the question 
asks the Subjects to assess the severity of acne, with a response ranging from ‘Clear’ to ‘Severe’, 
scored on a scale of 0 to 4. See Section 8.1 for general details on questionnaire scoring and 
administration. 
Patient Rating of Appearance 
ASIS Item # 10 asks the Subjects to rate how their face looked because of their Acne, with a 
response ranging from ‘Excellent’ to ‘Bad’, scored on a scale of 0 to 4. See Section 8.1 for 
general details on questionnaire scoring and administration. 
Parent/Caregiver Rating of AV Severity 
Parents/caregivers of children of age 12-17yrs will report their own perceived severity of 
children’s AV, in addition to the children providing their perceptions. This will be accomplished 
via a single item “Overall, how is your child’s acne on his/her face right now?”, with the 5-point 
likert response scales mimicking the Item # 9 in ASIS. This will be scored in the same way as the 
corresponding ASIS item. 
8.3.3 
Study Subject Assessments - Qualitative 
Subjects from a small subset of study sites will be asked to record a 1-3 minute audio (using the 
Mobile App) narrating their perceptions of treatment benefits associated with the sarecycline, at 
the end of their study participation or at Week 12, whichever comes earlier. This qualitative data 
will be used to ascertain attributes that study Subjects associate with sarecycline treatment in an 
un-prompted manner. 
8.3.4 
Study Subject Photographic Assessments 
Site Investigators from a subset of study sites will take photographs of facial acne of patients at 
baseline encounter and at Week 12, during the in-person visits. This photographic data will be 
used to document and depict the changes in acne severity that may be associated with sarecycline 
treatment in the study.  
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8.4 
Additional Subject Assessments 
Parent/Caregiver Worries about Acne 
The parents/caregivers of pediatric patients with AV will be asked - how worried they are about 
their child’s acne, with a response option of ‘not at all’ to ‘extremely’, and how concerned they 
are about their child’s ability to accomplish future goals and reach full potential due to acne, with 
a 5-point likert response scale of ‘not at all’ to ‘extremely’. These questions will be asked at 
baseline and Week 12. 
Concern about Antibiotics and Antibiotic Resistance 
Parents/caregivers and adult patients will be asked about their concerns about (themselves or 
their child) using antibiotics, or concerns about antibiotic resistance, with a 5-point likert 
response scale of ‘not at all’ to ‘extremely’. These questions will be assessed at baseline and at 
Week 12. 
Understanding of Acne-related Concerns 
Pediatric patients (of age 12-17) will be asked whether their parents understand their acne-related 
concerns, and correspondingly, the parents/caregivers will be asked whether they understand 
their child’s acne-related concerns. This pair of questions will have a response item on a 5-point 
likert scale of ‘not at all’ to ‘very much’. These questions will be asked at baseline and Week 12. 
8.5 
Compliance to Treatment 
Compliance with the assigned treatment regimen will be assessed by comparing the number of 
doses/tablets expected to be used, based on the total number of treatment days, with the actual 
number used (expressed as a percentage of used/expected) at each encounter and for the study 
overall. The actual consumption/use of study pills/tablets will be evaluated by assessing the left-
over pills/tablets in the medication bottles returned to sites/investigators by the Subjects. 
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8.6 
Safety Assessments 
8.6.1 
Definition of Adverse Events & Adverse Drug Reactions 
An AE is any untoward medical occurrence in a patient administered a pharmaceutical product 
which does not necessarily have a causal relationship with this treatment. An AE can therefore 
be any unfavorable and unintended sign, symptom, or disease temporally associated with the use 
of a medicinal product, whether or not related to the medicinal product. 
The Site Investigator will use the following terms to assess the severity of each AE:  
• Mild:  Awareness of symptoms or signs, but easily tolerated (acceptable).  
• Moderate:  Enough discomfort to interfere with usual activity (disturbing).  
• Severe:  Interferes significantly with ability to do work or usual activity (unacceptable).  
A Serious Adverse Event (SAE) is any experience that suggests a significant hazard, 
contraindication, side effect or precaution. With respect to human clinical experience, this 
includes any event which: 
• results in death, 
• is life-threatening, 
• requires inpatient hospitalization* or prolongation of hospitalization, unless 
hospitalization is for: 
o routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition. 
o elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since the start of study drug. 
o treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
o social reasons and respite care in the absence of any deterioration in the subject’s 
general condition. 
• results in persistent of significant disability / incapacity, or 
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• is a congenital anomaly / birth defect, 
• is a significant or important medical event that, based on appropriate medical judgment, 
may jeopardize the subject or may require intervention to prevent one of the other 
outcomes listed above. 
* Hospitalization is defined as an overnight (in-patient) stay at the hospital or emergency room. 
For all AEs (either related or not related to study medication), information about the outcome 
(resolved or ongoing) and the action taken with the study treatment (drug withdrawn, dose 
reduced, dose increased, dose not changed, not applicable) will be documented. 
Each AE, either serious or non-serious for which a causal relationship to sarecycline cannot be 
excluded, will be considered as an ADR. An ADR is an injury caused by taking medication. 
ADRs may occur following a single dose or prolonged administration of a medicinal product or 
result from the combination of two or more medicinal products.  
The determination of whether an AE is related to study treatment (sarecycline) will be based on 
information regarding the degree to which the study treatment had caused or contributed to the 
event and will be categorized per the following criteria: 
• Related:  There were good reasons and sufficient information (e.g. plausible time 
sequence, dose-response relationship, pharmacology, positive de-challenge and/or re-
challenge) to assume a causal relationship with the study medication in the sense that it is 
plausible, conceivable or likely. 
• Not Related:  There were good reasons and sufficient information (e.g. implausible time 
sequence and/or attributable to concurrent disease or other drugs) to rule out a causal 
relationship with the study medication. 
8.6.2 
Documentation and Reporting of ADRs, Events with Fatal Outcome 
and Other Reportable Events 
The Site Investigator is responsible for assessing and documenting (in subject medical charts, as 
part of usual care) all AEs that occur at any time during the study. The Site Investigator will 
determine the relatedness, seriousness, and severity for each AE, which is then recorded in the 
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Adverse Events page of the eDCF, per study schedule of events (Appendix A). Following each 
subject encounter (be it, via in-person or remote encounters), the Site Investigator will evaluate 
the last 4-weeks of documentation (in subject medical charts) to report AEs and indicate whether 
those events resulted in stoppage or changes to dose of study medication. 
 
Each AE that meets the definition of ADR will be recorded in the Adverse Events page of the 
eDCF and comprehensively documented on the “Adverse Drug Reaction” form to be reported 
within 1 working day (24 hours) of learning of the event and proactively reported to the Almirall 
LLC, CRO Safety Team via email or fax. ADR reporting details will be included in the Safety 
Reporting Plan. 
 
For the purpose of this study, all AEs that meet the aforementioned definition of an SAE (in 
Section 8.6.1) that occurred during the treatment period will be reported to the sponsor as SAEs. 
Upon receipt of SAE data by the study CRO (collected as part of eDCF), they will be reported 
within 1 working day (24 hours) of learning of the event to the sponsor regardless of its 
relationship to the study treatment. If any additional information is needed to adequately 
document the SAEs, the study CRO will follow-up with the Site Investigators to ensure data 
completeness and will report the updated information back to the study sponsor. If an SAE 
results in modification of study medication dose or discontinuation of study medication and/or 
withdrawal of subject from the study, such information will be documented as part of eDCF and 
reported to the study sponsor. 
 
As part of usual care, Site Investigator will follow Subjects concerning all SAEs and ADRs until 
adequate resolution or stabilization.  If the SAE/ADR has not resolved or stabilized by the time 
the subject completed the final study visit, the Site Investigator may gather the status of the 
subject’s SAE/ADR within 30 days beyond the subject’s final study visit, if required. 
 
If a study subject (in case of female) becomes pregnant during the study period, the Site 
Investigator may withdraw the patient from the study (i.e., early termination) for safety reasons. 
In this scenario, the Site Investigator will document the reasons for withdrawal in the eDCF and 
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may conduct necessary follow-ups with the patient to ensure safety, as part of usual care. 
Occurrence of this (pregnancy) event will be reported to the study sponsor within 1 working day 
(24 hours) of learning of the event. 
 
In addition, all events with a fatal outcome and all other reportable events (lack of effectiveness 
of sarecycline, overdose, off-label use, misuse, abuse, medication error or occupational 
exposure) – even in the absence of an ADR – will be documented on the “Adverse Drug 
Reaction” form and reported to the study sponsor within 1 working day (24 hours) of learning of 
the event. 
 
Early terminated patients will be evaluated for safety assessments at the time of next scheduled 
encounter, as feasible. This will be documented in the eDCF. 
 
9 STUDY OVERSIGHT 
The overall study principal investigators (PIs) along with the principal investigator (Program 
Lead) at CRO will be responsible for this real-world study oversight, including monitoring 
safety, ensuring that the study is conducted according to the protocol and ensuring data integrity. 
The Program Lead within the CRO will review the data for safety concerns and data trends at 
regular intervals, and will promptly report to the study PIs, the central IRB (and any local IRBs, 
if applicable) and to the study Sponsor any ADRs, protocol deviation, or any other significant 
event that arises during the conduct of the study. 
 
10 SITE MONITORING, QUALITY CONTROL AND ASSURANCE 
Study site monitoring is conducted to ensure that the rights of human Subjects are protected, that 
the study is implemented in accordance with the protocol and/or other operating procedures, and 
that the quality and integrity of study data and data collection methods are maintained. Site 
monitoring for this minimal-risk, real-world study will be performed by the CRO. The CRO will 
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routinely evaluate study processes and documentation based on the protocol and other applicable 
requirements, if any. 
All site monitoring activities will be performed remotely for this study, with occasional visits to 
select sites to check on study procedures. Site Investigators or the assigned study coordinators 
will be contacted routinely by phone and email to ensure that study procedures are followed per 
protocol and study subject follow-ups happen as planned. Study data review will be undertaken 
by the CRO staff following the baseline and follow-up encounters for data collection from Site 
Investigators and study Subjects. Data inquiries will be shared with the Site Investigators for 
clarification and/or fill missing data elements, or gather additional information, as it may pertain 
to reported AEs/SAEs. 
 
11 DATA MANAGEMENT 
The study data portal will comprise of two distinct, linked data sources, one being the traditional 
EDC containing eDCF to gather data from Site Investigators; another being the mobile App that 
gathers data directly from study Subjects. The back-end EDC platform will be programmed with 
edit checks to ensure that the incoming data from Site Investigators and Subjects are routinely 
checked for data quality, any systematic missing data, trends in select outcome measures and 
safety events.  
A centralized data review strategy will ensure consistency, integrity, logical completeness, and 
coding of collected data. Queries will be generated for study sites to solicit additional required 
information, as needed. Any necessary data corrections in the EDC portal at the back-end will be 
made by the central research staff, and ratified by the CRO Program Lead for appropriateness 
and correctness. 
Incoming AE data will be routinely checked to flag SAEs and other pertinent high-priority safety 
events, gather additional information from the sites (as/if needed), and additionally collected 
information will be integrated back with the master study dataset, while the safety data is 
processed for expedited reporting to study sponsor. 
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Any additional quality assessment(s) will be carried out for the study per the study specific data 
management plan. Following completion of all data review activities for all patients, records 
within the master dataset will be locked, followed by completion of medical coding for 
concomitant medications and adverse events and preparation of dataset for statistical analyses. 
 
12 STATISTICAL CONSIDERATIONS 
Detailed plans for the statistical methods will be provided in a Statistical Analysis Plan (SAP) 
which will be finalized prior to database lock. 
 
12.1 
Sample Size Considerations 
No formal sample size and power calculations were undertaken. Considering the descriptive nature 
of the study and the feasibility of recruiting the study population, approximately 300 study Subjects 
from across a maximum of 50 clinical sites for the entire study has been identified as a sample to 
guide the planned analysis addressing the study objectives. 
 
12.2 
Analysis Populations and Datasets 
Statistical analysis and data tabulation will be performed using the following analysis 
populations unless specified otherwise: 
• Safety Population: All patients who received at least one dose of sarecycline during the 
study observation period, as part of usual care. 
• Full Analysis Set (FAS): All patients within the Safety Population that had at least some 
data pertaining to study primary research objective. 
 
There is a likelihood that the Safety population and FAS may be the same in certain scenarios, 
including when no patient discontinues sarecycline following study enrollment and prior to 3-
month follow-up data collection. In such scenarios, FAS will be the main dataset for all analyses. 
In the event that the safety population and FAS differ, all safety evaluations (part of additional 
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objectives) will be conducted among the safety population, while FAS will be used to conduct 
analyses addressing rest of the study objectives, including the primary objective. 
 
12.3 
General Statistical Procedures 
12.3.1 
Overview 
Data from Site Investigators and study Subjects will be combined into one dataset. No site-specific 
analyses will be conducted. Validated instruments will be scored according to developer 
guidelines, reporting domain scores and overall summary scores, as appropriate. Home-grown 
questions/items will be analyzed and reported individually, based on the respective response 
scales.  
 
Statistical differences in discrete variables will be assessed using a χ2 test. Continuous measures 
will be assessed using the appropriate parametric or nonparametric test. P values ≤ 0.05 will be 
considered significant in all analyses. All statistical analyses will be based on all available data 
assuming that all missing data are uninformative and will be conducted using appropriate statistical 
software, such as SAS. 
 
The final study analyses will be conducted after the completion of 12 weeks of data collection 
for all study Subjects.  
 
12.3.1 Summary Statistics 
The descriptive statistics for all the continuous variables will include the mean, median, 25th 
percentile, 75th percentile, standard deviation (SD), standard error of mean (SEM),  
minimum, maximum, and number of Subjects. Descriptive summaries will be provided for 
raw, CFB, and %CFB values for relevant endpoints, where applicable. Frequency distributions for 
all the categorical variables will be presented as counts and percentages. Summaries will be 
provided by encounters, as appropriate. Results from the descriptive analyses will be presented as 
summary tables and figures. 
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12.3.2 Subgroup Analysis  
Primary and additional outcome measures may be summarized and repeated for the following 
subgroups, only if sample size allows by study visit using FAS: 
• Gender: male and female 
• Age groups: 9 to 17 years and ≥ 18 years  
• Race: white, African-American/Black, other  
• Body mass index: < 25 kg/m2 and ≥ 25 kg/m2 
• Baseline facial IGA score: moderate and severe  
• Oral contraceptive use in females:  female Subjects who use oral contraceptives versus 
female Subjects who do not (if sample size permits) 
 
12.3.3 Multivariate Analyses 
CFB in key study outcome measures at Week 12 post-index date, and at Weeks 4 and 8 (if 
applicable) post-index date will be assessed using relevant multivariate analyses, adjusting for 
subject baseline characteristics and other variables (such as medication adherence) to discern 
the factors influencing these outcomes, as feasible. Repeated measures analyses with covariates 
may be used to statistically test the changes/trends for relevant outcome measures over time.  
 
Pearson correlation coefficients may be used to assess the correlation between key outcome 
measures; this may also inform the consideration of covariates in select multivariate analyses 
(to reduce multicollinearity).  
 
12.4 
Primary Endpoint Analysis 
The primary endpoint of PROs at Week 12 will be assessed descriptively, using the FAS dataset.  
For ASIS questionnaire, the individual item and domain/subscale scores will be created per 
instrument developer instructions, analyzed descriptively for the baseline and Week 12 encounters, 
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treating the responses as categorical variables and/or continuous variable, as appropriate. For the 
overall questionnaire data evaluation, no missing data imputation will be applied to compute 
domain/subscale scores. 
The Patient Global Assessment (PtGA) of acne severity based on the single ASIS item (# 9) will 
be analyzed separately using descriptive statistics and reported for Week 12. Specifically, 
proportion of Subjects who reported clear (0) and almost clear (1) on the item scale at Week 12 
will be assessed. Last Observation Carried Forward (LOCF) data imputation method will be used 
to impute responses to ASIS item # 9 at Week 12 for the Subjects with missing data at Week 12. 
Patient self-rating of their appearance based on the single ASIS Item (# 10) will be analyzed 
separately using descriptive statistics and reported for Week 12. Specifically, proportion of 
Subjects reporting "very good" or "excellent" at Week 12 will be assessed. LOCF data imputation 
method will be used to impute responses to ASIS item # 10 at Week 12 for the Subjects with 
missing data at Week 12. 
For Expert Panel Questionnaire, the items will be analyzed individually, using descriptive statistics 
and reported for Week 12.  
For all PRO elements, descriptive statistics will be computed, stratified by age and other relevant 
subgroups, to explore the relationship between these HRQoL items and subject characteristics.  
 
12.5 
Secondary Endpoint Analysis 
The secondary endpoint of the study is the proportion of patients with Facial IGA success at Week 
12, defined as a 2-point decrease in IGA score from baseline and a score of 0 (clear) or 1 (almost 
clear). The analyses of IGA success will be conducted for the overall cohort (using FAS), as well 
as stratified by age and other relevant subgroups. Relationship between this endpoint and subject 
characteristics will be explored using descriptive analyses. LOCF data imputation method will be 
used to impute responses at Week 12 for the Subjects with missing data at Week 12. 
 
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12.6 
Additional Analysis 
12.6.1 Treatment Satisfaction Analyses  
Investigator’s global satisfaction with sarecycline treatment will be analyzed using data at Week 
12 from a single question: “how satisfied are you with sarecycline treatment outcomes”, with 
response options ranging from ‘Very Satisfied’ to ‘Very Dissatisfied’. Frequency of responses 
will be tallied for all Subjects. Proportion of Subjects for whom Investigators indicated ‘Very 
Satisfied’ or ‘Satisfied’ will be reported. 
The analyses will be done for the overall cohort, using FAS, and stratified by age and other 
relevant subgroups. Relationship between Investigator satisfaction and subject characteristics 
will be explored using descriptive analyses. 
 
12.6.2 Treatment Compliance  
Compliance will be assessed by comparing the expected number of doses taken, based on the 
total number of treatment days between the encounters/surveys and within the entire treatment 
period of the study, with the number of unused doses/tablets identified/returned at each 
encounter/visit.  Treatment compliance will be calculated for each subject/visit and over all visits 
for the Safety population. Compliance values that are less than 0% will be set to 0%.  Summaries 
will be presented using descriptive statistics for the Safety population. 
Compliance = [# Expected to be used - # Unused] / [# Expected to be used] 
 
12.6.3 Comparison of Investigator and Subject Assessment of AV Severity 
The IGA and Subject perception of AV severity at Week 12 will be compared and reported using 
descriptive statistics, to portray the level of concordance/discordance in stakeholder perceptions. 
This analysis will be conducted for the entire cohort and for select subgroups. Correspondingly, 
the Investigator and Subject responses to the questions related to AV severity at baseline will 
also be compared and reported using descriptive statistics. The baseline level of 
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concordance/discordance between the stakeholders may be used to further stratify the Week 12 
data analyses. 
12.6.4 CFB in PROs  
CFB in ASIS domain scores and subscale scores at Week 12 will be assessed. CFB will be first 
analyzed descriptively for the entire cohort and select subgroups. Analyses will be provided for 
FAS. For this analysis, the domain scores will be considered as continuous variables. No missing 
data imputation will be used. Scoring, scaling, and the handling of missing data will be handled in 
accordance with the recommendations accompanying the ASIS documentation and will be 
described in more detail in the SAP.  
 
CFB in select individual items of ASIS, most specifically, items # 9 & 10, will be conducted by 
treating these variables as continuous variables. Based on data availability, CFB at Weeks 4 & 8 
will be assessed in addition to Week 12. CFB will be first analyzed descriptively for the entire 
cohort and select subgroups. LOCF data imputation method will be used to impute responses to 
ASIS items # 9 & 10 for respective encounters for the Subjects with missing data at those 
encounters, prior to analyses. 
 
Items from Expert Panel Questionnaire will be analyzed individually and CFB in individual 
questions/items will be reported for relevant categories of responses (depending on the response 
scales) descriptively. More detailed portrayal of this planned analysis will be outlined in the study 
SAP. No missing data imputation will be undertaken for these items. 
12.6.5 Comparison of Parent/Caregiver and Patient Perceptions of AV 
Severity and Impact 
Parent/caregiver and pediatric patient responses to the questions related to AV severity at Week 
12 will be compared and reported using descriptive statistics, to portray the level of 
concordance/discordance in stakeholder perceptions, within the Subject age group of 12-17 yrs. 
This analysis will be conducted for the entire relevant cohort and for select subgroups, if sample 
size permits. 
 
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Responses to select Expert Panel Questionnaire items at Week 12 related to worries about Acne 
and impact of acne on child’s lives will be compared to corresponding questions to 
parents/caregivers to portray the level of concordance/discordance in stakeholder perceptions, 
within the Subject age group of 12-17 yrs. This analysis will be conducted for the entire relevant 
cohort and for select subgroups, if sample size permits. 
 
Parent/caregiver and pediatric patient responses to the questions at Week 12 related to the 
parents’ understanding of child’s concerns will be compared and reported using descriptive 
statistics, to portray the level of concordance/discordance in stakeholder perceptions, within the 
Subject age group of 12-17 yrs. This analysis will be conducted for the entire relevant cohort and 
for select subgroups, if sample size permits. 
 
No missing data imputation will be undertaken for these items. 
12.6.6 Safety Assessments  
The safety data will be analyzed descriptively using Safety Population dataset (if it is different 
from FAS), to report the frequency of occurrences of AEs/ADRs and SAEs. These will be 
reported at individual item level as well in aggregate at specific category level (e.g., GI effects, 
vestibular effects) for each of the subject encounter timepoints (4, 8 & 12 weeks post-index 
date). The number of patients discontinuing treatment within the 3-month post-index date, and 
number of patients discontinuing the study within the entire study observation window (of 12 
weeks) because of AEs/ADRs will be reported, as documented in patient medical charts. 
12.7 
Missing Data Handling 
The missing data pertinent to the validated instrument ASIS will be handled per instrument 
owner instructions / scoring manual. For effectiveness measures obtained from Site 
Investigators and Subjects, namely, IGA, PtGA (from ASIS item # 9) and Patient appearance 
rating scale (from ASIS item # 10), LOCF data imputation method will be used to impute 
responses for Week 12 for the Subjects with missing data at Week 12. LOCF may also be used 
to impute responses for Weeks 4 & 8 for the Subjects with missing data at those encounters for 
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these select measures, as feasible. For all other study variables and endpoints, no missing data 
imputation is planned. 
12.8 
Sensitivity Analyses 
Sensitivity analyses will explore the impact of missing data on the robustness of the results. 
Reasons for missing data and time to drop-out will be explored in a descriptive fashion. The key 
study outcomes will be explored for Subjects that completed the study versus those that 
discontinued the study, using descriptive statistics and multivariate regression models, as 
appropriate. If some Subject visits are conducted via remote visits instead of in-person visits, the 
nature of visit (remote vs. in-person) may be used to stratify the analysis of secondary endpoint 
involving IGA. The dataset with LOCF imputed values will be used to repeat only the select 
outcomes analyses as outlined in Section 12.7 and the results will be shown along with the results 
from analyses without LOCF data imputation. 
 
Details of the sensitivity analyses will be described in SAP prior to database lock. 
 
13 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS 
Study staff will maintain appropriate medical and research records for this study for the integrity 
of research and protection of confidentiality of Subjects. Study staff will permit authorized 
representatives of the IRB and study CRO to examine research records for the purposes of 
quality assurance reviews, audits, and evaluation of the study safety and progress. 
The eDCFs represent a record of the subject’s experience in the study, therefore, the eDCF data 
will be supported by original (or source) medical records, where feasible. Prior to enrolling a 
subject in the study, the s Site Investigator or site staff will document his/her review of subject 
eligibility criteria in the source records for the subject. Current or changes in clinical 
characteristics of the AV patients, including current or changes to disease severity and 
medications will be documented in patient medical charts as part of routine clinical practice, and 
these may constitute source records for the Subjects. Data recorded directly into the eDCF (via 
online portal) is also considered source data when there are no other written or electronic records 
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preceding the eDCF entry; data from online surveys completed by study Subjects will be 
considered as source data, with no back-up records (or data copies) in patient medical charts. 
No study monitoring visits will be conducted by the CRO as part of the study, as the sites and 
Subjects will be managed remotely, and all data will be collected using eDCFs. Occasional visits 
to select sites may be conducted (only as feasible) to monitor the progress of the study.  
The electronically collected data will be periodically reviewed to evaluate the progress of the 
study; to verify the accuracy and completeness of eDCFs; to ensure that all protocol 
requirements, and Investigator’s obligations are being fulfilled; and to resolve any inquiries 
related to the study data.  
The Site Investigators agrees that the Study CRO or the IRB will have reasonable access to study 
source documentation (albeit, in de-identified manner) for purposes of audit both during and 
after completion of the study. 
 
14 ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1 
Ethical Standard 
The investigators will ensure that this study is conducted in full conformity with the principles 
set forth in The Belmont Report: Ethical Principles and Guidelines for the Protection of Human 
Subjects of Research, as drafted by the US National Commission for the Protection of Human 
Subjects of Biomedical and Behavioral Research (April 18, 1979) and codified in 45 CFR Part 
46 and/or the ICH E6. 
 
14.2 
Institutional Review Board 
The protocol, informed consent form(s), and all participant materials will be submitted to the 
IRB for review and approval. Approval of both the protocol and the consent form must be 
obtained before any participant is enrolled. Any amendment to the protocol will require review 
and approval by the IRB before the changes are implemented in the study.  A progress report will 
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be submitted by the Study CRO Program Lead to the IRB at intervals specified by the IRB, but 
not less than annually.  
 
14.3 
Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to participate in the 
study and continues throughout study participation.  
The participating Site Investigator will ensure that written informed consent (and/or assent, if 
applicable) is obtained from each subject (and parent(s) or legal guardian(s), if applicable) in 
accordance with applicable regulations. Subjects under the age of 18 must sign the Assent Form. 
The subject and their parent(s) or legal guardian(s), if applicable, will be given adequate time to 
consider the risks associated with participation in the study. Study Subjects may provide 
consent/asset using online data collection portal, in case of virtual study visits/encounters in the 
absence of in-person visits/encounters. Each subject will provide informed consent (and/or assent 
if applicable and according to IRB regulations) prior to participating in any study procedures, as 
outlined in Section 6.3.2 of this protocol. As an addendum to the main consent form, the Subjects 
from a small subset of sites will be consented (with necessary assent) to allow facial photographs 
taken at baseline and Week 12 by their clinician at the privacy of the clinician’s office and will 
be consented (with necessary assent) to provide a 1-3 minute testimonial of Subject’s experience 
with sarecycline (Seysara®) at Week 12. 
 
14.4 
Participant Confidentiality 
Participant confidentiality is strictly held in trust by the investigators, study staff, and the 
sponsor(s) and their agents. The final research data will constitute only de-identified data, for 
research analyses and reporting. Participants will be identified by a unique study ID number 
assigned by the site coordinator and/or study CRO, which will be listed on the paper-based 
consent forms or online e-consent forms and on each of the online e-DCFs. The site coordinator 
and the CRO project team may review the e-DCFs for any missing data periodically. Access to 
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the online e-DCFs will be restricted to the patient/caregiver, the site coordinator/Investigator, and 
the relevant representatives from the CRO. 
The study protocol, documentation, data, and all other information generated will be held in 
strict confidence. Site Investigator and study subject contact information will be collected strictly 
for administrative purposes, such as processing of incentives and to share study follow-up 
reminders. This personally identifiable information will remain separate from research data. 
Photographs to document baseline clinical status and Week 12 outcomes (of acne severity) 
associated with the use of study medication will be obtained from a small subset of study 
Subjects. Audio testimonials depicting Subject’s experience with sarecycline may be obtained 
from a subset of study Subjects at Week 12. All of these data will be stored electronically and 
anonymized (using appropriate digital technology) before using this data for further analyses 
and/or publications. 
No information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of the sponsor or the study CRO. The study CRO or other 
authorized representatives of the sponsor may inspect all study documents and records, but at no 
juncture will study subject identifiable information will be collected or disclosed. 
15 OTHER INFORMATION 
 
15.1 
Publication and Disclosure Policy 
Publication and disclosure policy is addressed in a separate agreement. 
 
15.2 
Termination of the Study 
If the study is terminated prematurely or suspended, the appropriate IRB will be promptly 
informed of the termination or suspension and will be provided the reason(s) for the termination 
or suspension.  All obligations and responsibilities of the Sponsor and the Investigator will 
remain in force if the study is terminated prematurely. 
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16 LITERATURE REFERENCES 
 
1. Alexis A et al. Development of a New Patient-Reported Outcome Measure for Facial Acne:  
The Acne Symptom and Impact Scale (ASIS). J Drugs Dermatol. 2014;13(3):333-340. 
2. Bhate K, Williams HC. Epidemiology of acne vulgaris. The British journal of dermatology 
2013; 168:474-85. 
3. Bickers DR, Lim HW, Margolis D, et al. The burden of skin diseases: 2004 a joint project of 
the American Academy of Dermatology Association and the Society for Investigative 
Dermatology. Journal of the American Academy of Dermatology 2006; 55:490-500. 
4. Cherynshov et al. Quality of life measurement in acne. Position Paper of the European 
Academy of Dermatology and Venereology Task Forces on Quality of Life and Patient 
Oriented Outcomes and Acne, Rosacea and Hidradenitis Suppurativa. J Eur Acad Dermatol 
Venereol. 2018 Feb;32(2):194-208. 
5. Deeks E. Sarecycline: First Global Approval. Drugs. 2019; 79:325–329. 
6. Del Rosso et al. Patient awareness of antimicrobial resistance and antibiotic use in acne 
vulgaris. J Clin Aesthet Dermatol. 2019; 12(6):30–41. 
7. Farrah G, Tan E. The use of oral antibiotics in treating acne vulgaris: a new approach. 
Dermatol Ther. 2016 Sep; 29(5):377-384. 
8. Gieler U et al. Acne and quality of life – impact and management. JEADV. 2015; 29 (Suppl. 
4):12–14. 
9. Kaye KS, Pogue JM. Infections Caused by Resistant Gram-Negative Bacteria: Epidemiology 
and Management. Pharmacotherapy. 2015 Oct; 35(10):949-62. 
10. Kircik LH. Doxycycline and minocycline for the management of acne: a review of efficacy 
and safety with emphasis on clinical implications. J Drugs Dermatol. 2010 Nov; 9(11):1407-
11. 
11. Lafrance, M., Carey, R. S. Skin Work: Understanding the Embodied Experience of Acne. 
Body & Society. 2018; 24(1-2), 55-87. 
12. Lasek RJ, Chren MM. Acne vulgaris and the quality of life of adult dermatology patients. 
Arch Dermatol. 1998; 134: 454-8. 
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13. Moore A et al. Once-Daily Oral Sarecycline 1.5 mg/kg/day Is Effective for Moderate to 
Severe Acne Vulgaris: Results from Two Identically Designed, Phase 3, Randomized, 
Double-Blind Clinical Trials. J Drugs Dermatol. 2018 Sep 1; 17(9):987-996. 
14. Revol O, Milliez N, Gerard D. Psychological impact of acne on 21st-century adolescents: 
decoding for better care. Br J Dermatol. 2015; 172(Suppl 1):52–58. 
15. Seite S et al. Interest of corrective makeup in the management of patients in dermatology. 
Clin Cosmet Investig Dermatol. 2012; 5:123–128. 
16. Thiboutot DM et al. Assessing effectiveness in acne clinical trials: steps towards a core 
outcome measure set. Br J Dermatol. 2019;181(4):700-706.  
17. Timms RM. Moderate acne as a potential barrier to social relationships: myth or reality? 
Psychol Health Med. 2013; 18(3):310–320. 
18. Tuchayi SM et al. Interventions to increase adherence to acne treatment. Patient Preference 
and Adherence 2016; 10:2091–2096. 
 
 
 
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17 APPENDICES 
 
Appendix A: Study Schedule of Events 
Appendix B: Select Study Questionnaires 
Appendix C: Signature Page 
 
 
 
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17.1 
APPENDIX A: Study Schedule of Events 
Study Encounter (physical or virtual) 
Baseline 
E1 
E2 
E3 
End of Study  
E4 
Early 
Termination 
Visit 
Week† 
 Wk 4 
(± 4 d) 
Wk 8 
(± 4 d) 
Wk 12 
(± 4 d) 
- 
Informed consent 
X 
 
 
 
 
Selection criteria 
X 
 
 
 
 
Demographics & baseline clinical characteristics1 
X 
 
 
 
 
Physical examination2 
X 
 
 
X 
X 
AV medical history and relevant comorbidites3 
X 
 
 
X 
X 
Seysara dose4 
X 
X 
X 
X 
X 
Dispensing and return of study medication 
X 
X 
X 
X 
X 
Prior acne medication (since diagnosis & past 6 months) 
X 
 
 
 
 
Concomitant general medication 
X 
 
 
X 
X 
Concomitant anti acne medication 
X 
 
 
X 
X 
Site Investigator’s clinical assessment of acne5  
X 
X 
X 
X 
X 
Study subject questionnaires6 
X 
X 
X 
X 
X 
AEs/SAEs7 
X 
X 
X 
X 
X 
Reasons for premature study withdrawal 
 
 
 
 
X 
† Expected in-person or virtual encounter/visit schedule, in relation to the index date (date of first administration of sarecycline). 
1 Clinical characteristics data assessed retrospectively based on what is documented in patient medical charts. 
2 Routine physical examination conducted as part of usual care alone and as documented in patient medical charts; such data may include - blood 
pressure, waist circumference, height/weight measurements. 
3 May include AV date of diagnosis, baseline severity, relevant comorbidities, per clinician judgment and/or as documented in patient medical 
charts immediately before the index date; new emerging comorbidities during the study period will be recorded, based on the documentation in 
patient medical charts. 
4 Expected usage is once daily, every day during the duration of the trial. 
5 Site Investigator assessments of AV severity of Subjects may be conducted during subject visit to clinician offices, or via remote/virtual (telehealth) 
visits owing to Covid-related travel restrictions. 
6 Subject self-assessments will include PtGA of acne severity; various HRQOL assessments will be conducted at baseline and Week 12. 
7 In the case of premature study discontinuation due to an AE, the Investigator should make every effort to collect the AE duration and outcome. 
Any SAE that is ongoing at the End of the Study or at the time of premature withdrawal will be followed up until the SAE is resolved or at least up 
to 4 weeks. AE follow-up information will be reported in the eDCF. 
 
Note: AE, adverse event; eDCF, electronic Data Collection Form; E, encounter; W, week. 
 
 
 
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17.2 
Appendix B: Select Study Questionnaires 
ASIS 
 
Please read and answer each of the following questions about acne signs and symptoms. Before answering each 
question, look in the mirror and think about the acne on your face.  Select one answer for each question that 
best describes your experience with acne right now.  There are no right or wrong answers.  
 
1. 
How oily is your face right now? 
 
Not at all 
□ 
A little 
□ 
Somewhat 
□ 
Quite a bit 
□ 
Very 
□ 
 
 
 
 
 
 
2.  
How many pimples do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
3. 
How many acne scars (holes or indents) do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
4. 
How many scabs from acne do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
5. 
How many dark marks from acne do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
6. 
How many blackheads do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
7. 
How many whiteheads do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
8. 
How much redness do you have on your face right now? 
 
None 
□ 
A few 
□ 
Some 
□ 
Quite a bit 
□ 
A lot 
□ 
 
 
 
 
 
 
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9. 
Overall, how is the acne on your face right now? 
 
Clear 
□ 
Almost clear 
□ 
Mild 
□ 
Moderate 
□ 
Severe 
□ 
 
 
 
 
 
 
Please read and answer each of the following questions about how acne impact your quality of life.  Before 
answering each question, look in the mirror and think about the acne on your face.  Select one answer for each 
question that best describes your experience with acne in the past 7 days.  There are no right or wrong answers. 
 
10. 
Over the past 7 days, rate how your face looked because of your acne. 
 
Excellent 
□ 
Very good 
□ 
Good 
□ 
Fair 
□ 
Bad 
□ 
 
 
 
 
 
 
11. 
Over the past 7 days, how often did you feel sad because of the acne on your face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
12. 
Over the past 7 days, how often did you feel embarrassed because of the acne on your face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
13. 
Over the past 7 days, how often did you feel self-conscious because of the acne on your face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
14. 
Over the past 7 days, how often did you feel annoyed because of the acne on your face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
15. 
Over the past 7 days, how often did you feel not confident because of the acne on your face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
16. 
Over the past 7 days, how often did you choose not to be around other people because of the acne on your 
face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
17. 
Over the past 7 days, how often did someone make bad comments about the acne on your face? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
CCI

PROSES Study Protocol                                                      
 
Version 1.0 
Protocol # M-24001-40 
18 March 2021 
 ________________________________________________________________________________________________________  
 
 
45 
 
 
 
Expert Panel Questionnaire 
 
Please read and answer each of the following questions about how acne affect your emotional wellbeing, social 
interactions, and other daily activities. Before answering each question, look in the mirror and think about the 
acne on your face.  Select one answer for each question that best describes your experience with acne over the 
past 7 days.  There are no right or wrong answers. 
 
1. 
Over the past 7 days, how often has your acne made you feel angry (mad/sad)? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
2.  
How worried are you about how long your acne will last and how bad it will get? 
 
Not at all 
□ 
Slightly 
□ 
Somewhat 
□ 
Moderately 
□ 
Extremely 
□ 
 
 
 
 
 
 
3. 
How often do you think about your acne? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
4. 
Over the past 7 days, how worried have you been about your acne? 
 
Not at all 
□ 
Slightly 
□ 
Somewhat 
□ 
Moderately 
□ 
Extremely 
□ 
 
 
 
 
 
 
5. 
How often do you change, edit, or filter your social media photo or selfie because of your acne? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
6. 
How often does acne impact your “in real-life” plans (IRL) (like dating or social engagements, playing 
sports, swimming or hanging out)? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
7. 
How often are you doing something to hide your acne (like mess with, squeeze/pop, or use makeup, 
concealer, hairstyle, clothes to cover up)? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
8. 
How often do you feel picked on or judged because of your acne? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
CCI

PROSES Study Protocol                                                      
 
Version 1.0 
Protocol # M-24001-40 
18 March 2021 
 ________________________________________________________________________________________________________  
 
 
46 
 
 
9. 
How concerned are you that your acne will affect your ability to reach your future goals (in school or work) 
and be the best you can be? 
 
Not at all 
□ 
Slightly 
□ 
Somewhat 
□ 
Moderately 
□ 
Extremely 
□ 
 
 
 
 
 
 
10. 
Over the past 7 days, how often has worrying about or discomfort (itching/hurting) from acne affected your 
sleep? 
 
Never 
□ 
Rarely 
□ 
Some of the time 
□ 
Most of the time 
□ 
All of the time 
□ 
 
 
 
 
 
 
 
CCI

PROSES Study Protocol                                                      
 
Version 1.0 
Protocol # M-24001-40 
18 March 2021 
 ________________________________________________________________________________________________________  
 
 
47 
 
 
17.3 
APPENDIX-C: Signature Page 
The signature below constitutes the approval of this protocol and the attachments, and provides 
the necessary assurances that this study will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to relevant legal and 
regulatory requirements. 
 
Study PIs (for Central IRB Purposes): 
 
 
Name  
 
 
 
 
Signature 
 
 
 
Date 
 
 
Name  
 
 
 
 
Signature 
 
 
 
Date 
 
Almirall Approvals: 
 
 
 MD 
  
Signature 
 
 
 
Date 
Global Medical Affairs 
 
 
 
 
 
  
 
Signature 
 
 
 
Date 
Global Development – R&D 
 
 
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
CCI