Pilot Study of Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa
Phase: PHASE1
Conditions: Hidradenitis Suppurativa, Hidradenitis, Acne Inversa, Boils, Follicular Occlusion Triad, Follicular Occlusion Tetrad
Sponsor: Elena Gonzalez Brant, MD

Hydroxychloroquine for the Treatment of Hidradenitis Suppurativa 
NCT #:03275870
 06/03/2019
                                                                           Page 1 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

1.0 Specific Aims
To evaluate the efficacy of hydroxychloroquine as a treatment for hidradenitis suppurativa (HS)
We will conduct a pilot trial of standard dosing of hydroxychloroquine in patients with HS
To identify biomarkers as possible therapeutic targets for the treatment of HS
We will evaluate the levels of inflammatory cytokines in the peripheral blood of patients with HS.
2.0 Background information
Hidradenitis suppurativa is a debilitating and mutilating disease and its pathogenesis is still 
poorly understood. It involves the development of recurrent, painful nodules in intertriginous 
areas that become inflamed, form abscesses that may rupture, and develop chronic fistula 
tracts. The cause of hidradenitis suppurativa (HS) is thought to be multifactorial and may begin 
with follicular occlusion and rupture, leading to a cascade of inflammatory responses in 
susceptible individuals. The disease has been associated with high body mass index, smoking 
and genetic predisposition. There is a known association between HS and the metabolic 
syndrome, an association that remains after controlling for body mass index 1 . HS 
predominantly affects women and ethnic minorities  2, 3 and the prevalence is thought to be as 
high as 2%, although embarrassment and lack of awareness may lead to an underestimate of 
the true burden of disease. 
Although HS is a fairly common disease, relatively little is understood about its pathogenesis. 
Immune dysregulation is thought to play a role in disease development. Increased levels of IL-
12, IL-17 and IL-23, TNFα, IL-10 and IL-1β were found to be expressed in lesional skin of HS 
patients 4, 5. Recent studies have also identified elevated levels of IL-17 in the serum of patients 
with HS 6 . 
HS is associated with a significant impact on patient quality of life  7 . Patients suffer from both 
the physical and psychological impact of disease. Many therapies have been used to treat HS, 
from topical antibiotics to oral retinoids to radical surgeries, but all have limited efficacy. Despite 
efforts to control disease, many patients live with chronic wounds and disability. The decision 
about appropriate therapy for HS, especially in the early stages, is mainly based on expert 
opinion, anecdotal evidence and small studies. Topical and systemic antimicrobial treatments 
are often used as first line therapies, although studies have repeatedly shown that the 
abscesses of HS are sterile or contain only normal flora. The mechanism of improvement with 
antimicrobials may be through alterations in the local microbiome. Significant improvement in 
disease has been seen with dual therapy with twice daily use of 300mg rifampicin and 300mg 
clindamycin 8, neither of which have an FDA indication for use in HS. Doxycycline is used 
frequently in HS, but little evidence supports this. Despite success with the above therapies, the 
risk of antimicrobial resistance is real, and is increased with frequent and prolonged use of 
these medications in HS 9 . Teratogenic effects, gastrointestinal upset and photosensitivity with 
use of tetracyclines, risk for clostridium difficile colitis with clindamycin, and antimicrobial 
resistance with rifampicin highlight a need for safer and effective therapeutic options for the 
treatment of early HS. 
For more advanced disease (Hurley stage II and III), the tumor necrosis factor inhibitor 
adalimumab is the only FDA approved biologic treatment for HS. It has shown promise in 
severe disease, but only ~50% of patients achieved a clinical response at 12 weeks, and this 
clinical response declined over time 10 . Additionally, newer biologic therapies have been used in 
small numbers of patients with HS with variable results. Importantly, the cost of these 
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   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

medications is considerable.
Hydroxychloroquine, initially developed as an antimalarial, has been used successfully for over 
70 years in the treatment of autoimmune disease. Its mechanism of action is still poorly 
understood, but it has been shown to have many varied immunomodulatory properties  11 . 
Evidence suggests that hydroxychloroquine has an effect on inflammatory disease through 
decreasing levels of TNFα 12 and Th-17 cytokines (including IL-6, IL-17 and IL-22)13 . Additionally,
studies have shown a beneficial effect of hydroxychloroquine on lipid metabolism and glucose 
14 . Patients with rheumatoid arthritis (which similarly to HS has an independent association with 
cardiovascular disease) who were treated with hydroxychloroquine had an overall decreased 
incidence of cardiovascular events 15 . Hydroxychloroquine has a relatively benign safety profile, 
with retinopathy being the most concerning long term side effect. The retinopathy caused by 
hydroxychloroquine is reversible if identified early, and standard protocols for the use of this 
medication include yearly ophthalmologic examination.
3.0 Experimental Design and Methods
We hypothesize that treatment with hydroxychloroquine may offer a safer and effective method 
to control disease activity in HS. We hypothesize that the profiling inflammatory cytokines in the 
peripheral blood of the patients with HS may provide novel therapeutic targets for the disease. 
Additionally, monitoring of inflammatory cytokines before and after treatment may help to 
explain the mechanism by which therapies work.  Over the proposed period, we intend to gather
data about patient response to treatment with hydroxychloroquine and about the cytokine profile
of patients with HS. Sequential patients will be assigned to hydroxychloroquine treatment. 
Patients will be evaluated at baseline and after 3 months of treatment for treatment response 
and to evaluate quality of life measures. Serum will be collected at baseline and following 3 
months of treatment. Peripheral blood from patients with HS will be analyzed for levels of 
cytokines thought to be involved in HS and several markers of inflammation that have not yet 
been analyzed in this disease. 
Treatment
Patients will have baseline CBC and CMP evaluation prior to initiation of therapy
Sequential patients will be assigned treatment with hydroxychloroquine 200mg BID
Treatment length will be 3 months
Evaluation of HS
Patients will be evaluated at baseline and at 3 months by:
Hurley staging: 
Stage 1: solitary or multiple, isolated abscess formation without scarring or sinus 
tracts
Stage 2: recurrent abscesses, single or multiple widely separated lesions, with 
sinus tract formation
Stage 3: diffuse or broad involvement, with multiple interconnected sinus tracts 
and abscesses
Number of inflammatory nodules, abscesses, fistulas, scars, locations of these lesions, longest 
distance between 2 relevant lesions, are lesions separated by normal skin (for 
Sartorius scoring)
Improvement in HS lesions
Sartorius score: A statistically significant decline in Sartorius scoring between baseline and end 
of treatment
                                                                           Page 3 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

Evaluation of quality of life
Patients will be asked to fill out Dermatology Life Quality Index  (DLQI) survey at baseline and 3 
months. It is a simple, validated 10-question questionnaire. Answers to the 
questionnaire will be entered into a database.
For general inflammatory skin conditions a change in DLQI score of at least 4 points is 
considered clinically important
Serum for evaluation
Peripheral blood will be collected at baseline and after 3 months of treatment. A 10 ml red top 
tube of venous blood will be obtained from patients at the time of enrollment and at 
month 3 for banking and cytokine analysis. The red top tubes will be centrifuged, 
sera will be aliquoted, logged in the database and stored indefinitely at -800C without 
identifiers by a technician in Dr. Akilov's laboratory.
Cytokine analysis
Using an inflammatory cytokine panel, levels of cytokines including L-1β, IL-4, IL-6, IL-10, IL-
17A, IL-17F, L-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α will
be evaluated at baseline and 3 months. Analysis will be performed at the 
University of Pittsburgh Cancer Institute Luminex core facility using multianalyte 
profiling. Levels will be compared to age, sex and BMI matched controls in our 
database.
Therapy may be discontinued for any of the following reasons:
Unacceptable adverse event(s),
Patient decides to withdraw from the study, or
General or specific changes in the patient’s condition render the patient unacceptable for further
treatment in the judgment of the investigator.
4.0 Human Subjects
Protection of Human Subjects
Human Subjects Involvement, Characteristics, and Design. The racial, gender and ethnic 
characteristics of the proposed subject population will reflect the demographics of 
Pittsburgh and the surrounding area and/or the patient population of the UPMC 
Health Systems.  We shall attempt to recruit subjects in respective proportions to 
these demographics. No exclusion criteria will be based on race, ethnicity, gender, or
socioeconomic status. The numbers of enrolled male to female subjects will be 
consistent with and reflective of the numbers of patients seen in the UPMCHS clinics
and in approximate 1:1 proportion. 
Sources of material. 
Information on the subject's medical history will be obtained relative to the inclusion and 
exclusion criteria. Data collection methods will include data obtained specifically for 
research purposes based on the most recent office note. All records related to this 
research study will be stored in a locked file cabinet. The subject’s identity on these 
records will be indicated by a case number rather than by name, and the information 
linking these case numbers will be kept separate from the research records.
Recruitment
Potential subjects with Hurley stage I/II hidradenitis suppurativa will be identified by the 
                                                                           Page 4 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

examining physician and referred for evaluation by the principal investigator or co-
investigator.  Subjects will be recruited from the UPMC dermatology department 
clinics. Potential subjects will be evaluated by the Principal Investigator, who is also 
the treating physician, during a routine clinic visit prior to any screening procedures 
or evaluation of the medical record for research purposes.  Potential subjects will be 
approached by physicians directly involved in their care.  No “cold calling” will occur. 
Informed consent will be obtained on all subjects by the principal investigator prior to 
all screening procedures.  If for any reason, a subject is excluded or resigns during 
the course of study, a new subject will be enrolled. 
Inclusion Criteria
Enrolled HS patients must be Hurley stage I or II (defined above)
Patients may be on topical therapy only, and/or have completed non-immunosuppressive 
therapy at time of enrollment.
Subjects must be 18 years of age and must be able to understand the written informed consent.
No evidence of active infection, regardless of the degree of severity or localization.  Subjects 
with active infections (whether or not they require antibiotic therapy) may be eligible 
after complete resolution of the infection. Subjects on antibiotic therapy must be off 
antibiotics for at least 7 days before beginning treatment.
Exclusion criteria
Subjects currently on systemic immunosuppression are ineligible
Subjects under 18 years of age
Due to small risk of retinopathy, hepatic disease, psoriasis exacerbation, exacerbation of 
porphyria cutanea tarda (PCT) in patients treated with hydroxychloroquine, subjects 
with known retinal disease, hepatic disease, psoriasis and PCT will be excluded
Due to potential fetal risk with use of hydroxychloroquine, pregnant patients or those planning to
become pregnant will be excluded
Risks to the subjects:
i.
The risks of the study are minimal and are related drug therapy and to obtaining the 
blood samples needed for our analysis. 
1.
Physical. 
a)
Small likelihood of drug toxicity. Hydroxychloroquine has been used for many 
years and is known to have a mild side effect profile. 
b)
Small likelihood of infection or bleeding. Risks minimized by proper protective 
equipment and hygiene
2.
Psychological. There is a small likelihood of low psychological risk if participants are 
upset by request to be involved in the study
7.
Benefits
i.
Benefits may accrue to patients with HS. Benefits may accrue to study subjects who 
participate through greater awareness leading to greater individual and community 
empowerment, enhanced knowledge of community assets as well as health 
concerns and needs, and enhanced skills related to performance of duties as study 
subjects. Outside of participants in research, all community members may also 
benefit from enhanced trust and reciprocity within the community. 
5.0 Statistical considerations
                                                                           Page 5 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

1. Sample size
i.
The study will involve 20 patients with hidradenitis suppurativa
ii.
The comparison of baseline Sartorius scores and level of the measured cytokines in 
peripheral blood from HS will be compared using a two-sided t test with a p value 
<0.05 for statistical significance.
iii.
The probability is 80% that the study will detect a difference at a two-sided 0.05 
significance level if the true difference between groups is 30%.
6.0 Adverse Reaction Reporting Requirements:
This study will use the CTC version 2.0 for toxicity and Adverse Event reporting. A copy of the 
CTC version 2.0 can be downloaded from the CTEP home page (http://ctep.info.nih.gov). All 
appropriate treatment areas should have access to a copy of the CTC version 2.0.  All Serious 
Adverse events that require reporting to the FDA will be reported on the FDA 3500 medwatch 
form found in Appendix B
i.
The following adverse reactions must be reported in the manner described below. 
ii.
All adverse events which are considered to be related to the research study must be reported to
the University of Pittsburgh Cancer Institute (UPCI)
iii.
All serious adverse events that meet the University of Pittsburgh Institutional Review Board’s 
criteria for reporting can be found at (http://irb.pitt.edu)
Unexpected, 
fatal or life 
threatening and
associated with 
study drug
Unexpected, of 
moderate or 
greater severity
(But not fatal or 
life threatening)
and are 
associated with 
the research 
intervention
Serious, 
unexpected 
event that is 
associated with 
the study drug
Unexpected 
fatal
or life-
threatening
experience 
which is 
associated with 
the study drug
Call to UPCI 
within 24 hours 
at (412) 647-
8074
              X
  
Notify IRB within 
24 hours
              X
Notify UPCI as 
soon as 
               X
                                                                           Page 6 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

possible & local 
IRB within 10 
days
FDA notification 
within 15 days
               X
FDA notification 
within 7 days
                X
An adverse reaction is considered serious if it is fatal or life-threatening; requires or 
prolongs hospitalization; produces a disability; or results in a congenital anomaly/birth 
defect.
An adverse reaction is considered to be of moderate or greater severity if it requires 
medical evaluation (such as additional laboratory testing) and/or medical treatment; or if 
it is a serious adverse reaction.
An adverse reaction is considered to be unexpected if it is not identified in nature, 
severity or frequency in the current IRB-approved research protocol or informed consent 
document.
An adverse reaction is considered to be associated with the research intervention if 
there is a reasonable possibility that the reaction may have been caused by the research
intervention (i.e., a causal relationship between the reaction and research intervention 
cannot be ruled out by the investigators).
UPCI requires ADRs to be reported on the Medwatch form and on the University of 
Pittsburgh IRB adverse event form. The University of Pittsburgh Adverse event form 
must be signed by the treating investigator. 
(See Appendix A for copies of the Adverse event reporting forms).
 
iv.
FDA Guidelines for Adverse Event Reporting
All adverse events meeting the definition of serious, unexpected and associated to the 
research intervention will be reported to the IRB according to their guidelines found at 
(http://irb.pitt.edu):
Associated with the use of the drug. There is a reasonable possibility that the experience
may have been caused by the drug. 
Disability:  A substantial disruption of a person's ability to conduct normal life functions. 
Life threatening adverse drug experience. Any adverse drug experience that places the 
patient or subject, in the view of the investigator, at immediate risk of death from the 
reaction as it occurred, i.e., it does not include a reaction that, had it occurred in a more 
severe form, might have caused death. 
                                                                           Page 7 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

Serious adverse drug experience: Any adverse drug experience occurring at any dose 
that results in any of the following outcomes: death, a life threatening adverse drug 
experience, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant disability/ incapacity, or a congenital anomaly/birth defect. 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered a serious adverse drug experience when, based upon
appropriate medical judgment, they may jeopardize the patient or subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in this 
definition
Unexpected adverse drug experience: Any adverse drug experience, the specificity or 
severity of which is not consistent with the current investigator brochure; or, if an 
investigator brochure is not required or available, the specificity or severity of which is 
not consistent with the risk information described in the general investigational plan or 
elsewhere in the current application, as amended. "Unexpected," as used in this 
definition, refers to an adverse drug experience that has not been previously observed 
(e.g., included in the investigator brochure) rather than from the perspective of such 
experience not being anticipated from the pharmacological properties of the 
pharmaceutical product. 
7.0 Reporting of results
Following acquisition of the descriptive data and the calculation of formal statistics, 
manuscript(s) will be prepared for submission to peer reviewed journals.
8.0 Costs and Payments
Neither subject, nor their insurance provider, will be charged for the costs of any of the 
procedures performed for the sole purpose of this research study (i.e., the Screening 
Procedures, Experimental Procedures, or Monitoring Procedures described above). Subjects 
will be charged, in the standard manner, for any procedures performed for their routine medical 
care.
References
1. Gonzalez-Lopez MA, Hernandez JL, Lacalle M, Mata C, Lopez-Escobar M, Lopez-Mejias R, 
et al. Increased prevalence of subclinical atherosclerosis in patients with hidradenitis 
suppurativa (HS). J Am Acad Dermatol. 2016 Aug;75(2):329-35.
2. Nicola WG, Khayria MI, Osfor MM. Plasma testosterone level and the male genital system 
after chloroquine therapy. Boll Chim Farm. 1997 Jan;136(1):39-43.
3. Garg A, Lavian J, Lin G, Strunk A, Alloo A. Incidence of hidradenitis suppurativa in the united 
states: A sex- and age-adjusted population analysis. J Am Acad Dermatol. 2017 Mar 9.
4. Schlapbach C, Hanni T, Yawalkar N, Hunger RE. Expression of the IL-23/Th17 pathway in 
lesions of hidradenitis suppurativa. J Am Acad Dermatol. 2011 Oct;65(4):790-8.
5. van der Zee HH, de Ruiter L, van den Broecke DG, Dik WA, Laman JD, Prens EP. Elevated 
levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10 in hidradenitis 
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   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612

suppurativa skin: A rationale for targeting TNF-alpha and IL-1beta. Br J Dermatol. 2011 
Jun;164(6):1292-8.
6. Matusiak L, Szczech J, Bieniek A, Nowicka-Suszko D, Szepietowski JC. Increased interleukin
(IL)-17 serum levels in patients with hidradenitis suppurativa: Implications for treatment with 
anti-IL-17 agents. J Am Acad Dermatol. 2017 Apr;76(4):670-5.
7. von der Werth JM, Jemec GB. Morbidity in patients with hidradenitis suppurativa. Br J 
Dermatol. 2001 Apr;144(4):809-13.
8. Andersen RK, Jemec GB. Treatments for hidradenitis suppurativa. Clin Dermatol. 2017 Mar - 
Apr;35(2):218-24.
9. Fischer AH, Haskin A, Okoye GA. Patterns of antimicrobial resistance in lesions of 
hidradenitis suppurativa. J Am Acad Dermatol. 2017 Feb;76(2):309,313.e2.
10. Kimball AB, Okun MM, Williams DA, Gottlieb AB, Papp KA, Zouboulis CC, et al. Two phase 
3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016 Aug 4;375(5):422-34.
11. Rainsford KD, Parke AL, Clifford-Rashotte M, Kean WF. Therapy and pharmacological 
properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus,
rheumatoid arthritis and related diseases. Inflammopharmacology. 2015 Oct;23(5):231-69.
12. van den Borne BE, Dijkmans BA, de Rooij HH, le Cessie S, Verweij CL. Chloroquine and 
hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-
gamma production by peripheral blood mononuclear cells. J Rheumatol. 1997 Jan;24(1):55-60.
13. Silva JC, Mariz HA, Rocha LF,Jr, Oliveira PS, Dantas AT, Duarte AL, et al. 
Hydroxychloroquine decreases Th17-related cytokines in systemic lupus erythematosus and 
rheumatoid arthritis patients. Clinics (Sao Paulo). 2013 Jun;68(6):766-71.
14. Hage MP, Al-Badri MR, Azar ST. A favorable effect of hydroxychloroquine on glucose and 
lipid metabolism beyond its anti-inflammatory role. Ther Adv Endocrinol Metab. 2014 
Aug;5(4):77-85.
15. Sharma TS, Wasko MC, Tang X, Vedamurthy D, Yan X, Cote J, et al. Hydroxychloroquine 
use is associated with decreased incident cardiovascular events in rheumatoid arthritis patients.
J Am Heart Assoc. 2016 Jan 4;5(1):10.1161/JAHA.115.002867.
                                                                           Page 9 of 9                                          
          
   University Of Pittsburgh         
     Institutional Review Board   
Approval Date: 6/3/2019
Renewal Date:  6/2/2020
IRB #:   PRO17030612