Topical Tofacitinib for the Treatment of Alopecia Areata and Its Variants
Phase: PHASE2
Conditions: Alopecia Areata, Alopecia Totalis, Alopecia Universalis
Sponsor: Yale University



Page 2 of 26 
 
Does the principal investigator, or do any research personnel who are responsible for the design, 
conduct or reporting of this project or any of their family members (spouse or dependent child) 
have an incentive or interest, financial or otherwise, that may affect the protection of the human 
subjects involved in this project, the scientific objectivity of the research or its integrity? Note: 
The Principal Investigator (Project Director), upon consideration of the individual’s role and 
degree of independence in carrying out the work, will determine who is responsible for the 
design, conduct, or reporting of the research.  
See Disclosures and Management of Personal Interests in Human Research 
http://www.yale.edu/hrpp/policies/index.html#COI  
ο  Yes  
   
  No 
 
 
Do you or does anyone on the research team who is determined by you to be responsible for the 
design, conduct or reporting of this research have any patent (sole right to make, use or sell an 
invention) or copyright (exclusive rights to an original work) interests related to this research 
protocol? 
ο  Yes  
   
  No 
 
         
If yes to either question above, list names of the investigator or responsible person: 
 
The Yale University Principal Investigator, all Yale University co-investigators, and all Yale 
University individuals who are responsible for the design, conduct or reporting of research must 
have a current financial disclosure form on file with the University’s Conflict of Interest Office. 
Yale New Haven Hospital personnel who are listed as con-investigators on a protocol with a 
Yale University Principal Investigator must also have a current financial disclosure form on file 
with the University’s Conflict of Interest Office. If this has not been done, the individual(s) 
should follow this link to the COI Office Website to complete the 
form:  http://www.yale.edu/coi/   
 
NOTE: The requirement for maintaining a current disclosure form on file with the University’s 
Conflict of Interest Office extends primarily to Yale University and Yale-New Haven Hospital 
personnel.  Whether or not they are required to maintain a disclosure form with the 
University’s Conflict of Interest Office, all investigators and individuals deemed otherwise 
responsible by the PI who are listed on the protocol are required to disclose to the PI any 
interests that are specific to this protocol. 
 
SECTION II: GENERAL INFORMATION 
 
1. Performing Organizations:  Identify the hospital, in-patient or outpatient facility, school or 
other agency that will serve as the location of the research.  Choose all that apply: 
 
a. Internal Location[s] of the Study: 
 Magnetic Resonance Research Center   
   
 Yale University PET Center 
     (MR-TAC)                     
 YCCI/Church Street Research Unit (CSRU) 
 Yale Cancer Center/Clinical Trials Office (CTO)      YCCI/Hospital Research Unit (HRU) 
 Yale Cancer Center/Smilow        
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 YCCI/Keck Laboratories 

Page 3 of 26 
 
 Yale-New Haven Hospital               
 Yale-New Haven Hospital—Saint 
Raphael Campus 
 Cancer Data Repository/Tumor Registry 
 Specify Other Yale Location:     Yale Dermatology-Middlebury     
 
 
b. External Location[s]: 
 APT Foundation, Inc.             
 Haskins Laboratories 
 Connecticut Mental Health Center       
 John B. Pierce Laboratory, Inc. 
 Clinical Neuroscience Research Unit (CNRU)  Veterans Affairs Hospital, West Haven   
 Other Locations, Specify:            
 International Research Site  
(Specify location(s)): 
 
 
c. Additional Required Documents (check all that apply):   
 N/A 
*YCCI-Scientific and Safety Committee (YCCI-SSC)      
Approval Date:  
*Pediatric Protocol Review Committee (PPRC)        
Approval Date:  
*YCC Protocol Review Committee (YRC-PRC)        
Approval Date:     
*Dept. of Veterans Affairs, West Haven VA HSS        
Approval Date:  
*Radioactive Drug Research Committee (RDRC)        
Approval Date:  
 YNHH-Radiation Safety Committee (YNHH-RSC)      
Approval Date:  
 Magnetic Resonance Research Center PRC (MRRC-PRC)   Approval Date:  
 YSM/YNHH Cancer Data Repository (CaDR)         
Approval Date:  
 Dept. of Lab Medicine request for services or specimens form 
 Imaging on YNHH Diagnostic Radiology equipment request form (YDRCTO request) found 
at  http://radiology.yale.edu/research/ClinTrials.aspx) 
*Approval from these committees is required before final HIC approval is granted. See instructions 
for documents required for initial submission and approval of the protocol. Allow sufficient time for 
these requests. Check with the oversight body for their time requirements. 
 
2. Probable Duration of Project: State the expected duration of the project, including all 
follow-up and data analysis activities.  
12 months  
 
3. Research Type/Phase: (Check all that apply) 
a. Study Type 
     Single Center Study 
     Multi-Center Study 
Does the Yale PI serve as the PI of the multi-site study? Yes     No    
    Coordinating Center/Data Management 
    Other:  
b. Study Phase    N/A 
      Pilot    
 Phase I    Phase II    Phase III    Phase IV 
      Other (Specify):  
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 

Page 4 of 26 
 
4. Area of Research: (Check all that apply) Note that these are overlapping definitions and 
more than one category may apply to your research protocol. Definitions for the following 
can be found in the instructions section 4c: 
 Clinical Research: Patient-Oriented             
 Clinical Research: Outcomes and  
 Clinical Research: Epidemiologic and Behavioral                       Health Services 
 Translational Research #1 (“Bench-to-Bedside”) 
       
 Interdisciplinary Research 
 Translational Research #2 (“Bedside-to-Community”)     Community-Based Research 
 
5.   Is this study a clinical trial? Yes     No    
NOTE the current ICMJE (International Committee of Medical Journal Editors) definition of a 
clinical trial: “any research study that prospectively assigns human participants or groups of humans 
to one or more health-related interventions to evaluate the effects on health outcomes.” Health-related 
interventions include any intervention used to modify a biomedical or health-related outcome (for 
example, drugs, surgical procedures, devices, behavioral treatments, dietary interventions, and 
process-of-care changes). Health outcomes include any biomedical or health-related measures 
obtained in patients or participants, including pharmacokinetic measures and adverse events” 
     If yes, where is it registered? 
         Clinical Trials.gov registry    
         Other (Specify)  
 
Registration of clinical trials at their initiation is required by the FDA, NIH and by the ICMJE. 
 
If this study is registered on clinicaltrials.gov, there is new language in the consent form and compound 
authorization that should be used. 
For more information on registering clinical trials, including whether your trial must be 
registered, see the YCCI webpage, http://ycci.yale.edu/researchers/ors/registerstudy.aspx 
or  contact YCCI at 203.785.3482) 
6. Does the Clinical Trials Agreement (CTA) require compliance with ICH GCP (E6)?  
Yes    No   
 
7. Will this study have a billable service? A Billable Service is defined as a service or procedure 
that will be ordered, performed or result in charging in EPIC for individuals who are enrolled in 
a clinical research study, regardless if the charge is intended to be paid by the subject/their 
insurance or the research study. 
 
Yes    No   
If you answered "yes", this study will need to be set up in OnCore Support 
http://medicine.yale.edu/ymg/systems/ppm/index.aspx  
 
8. Are there any procedures involved in this protocol that will be performed at YNHH or one of its 
affiliated entities?  Yes ___ No __X_  If Yes, please answer questions a through c and note 
instructions below.  If No, proceed to Section III. 
a. Does your YNHH privilege delineation currently include the specific procedure
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 that you will 
perform? 

     
 
2. Research Team:  List all members of the research team. Indicate under the affiliation column whether 
the investigators or study personnel are part of the Yale faculty or staff, or part of the faculty or staff 
from a collaborating institution, or are not formally affiliated with any institution. ALL members of 
the research team MUST complete Human Subject Protection Training (HSPT) and Health 
Insurance Portability and Accountability Act (HIPAA) Training before they may be listed on the 
protocol.  See NOTE below. NOTE:  
3. The HIC will remove from the protocol any personnel who have not completed required 
training. A personnel protocol amendment will need to be submitted when training is completed. 
 
SECTION IV: 
 PRINCIPAL INVESTIGATOR/F
ACULTY ADVISOR/
 DEPARTMENT CHAIR AGREEMENT 
 
 
 
 
 
Principal 
Investigator 
Brett King, MD, PhD   Yale University School of Medicine   
 
Role: co-
investigator 
Brittany Craiglow, MD  Yale University School of Medicine   
 
Role: study 
personnel 
 Lucy Liu 
Yale University School of Medicine   
 
Role: 
  
 
Role: 
 
 
 
 
Role: 
 
 
 
 
As the principal investigator of this research project, I certify that: 
 The information provided in this application is complete and accurate. 
 I assume full responsibility for the protection of human subjects and the proper conduct of the 
      research. 
 Subject safety will be of paramount concern, and every effort will be made to protect subjects’ 
      rights and welfare. 
 The research will be performed according to ethical principles and in compliance with all federal, 
      state and local laws, as well as institutional regulations and policies regarding the protection of   
      human subjects. 
 All members of the research team will be kept apprised of research goals. 
 I will obtain approval for this research study and any subsequent revisions prior to my initiating the 
      study or any change and I will obtain continuing approval of this study prior to the expiration date      
      of any approval period. 
 I will report to the HIC any serious injuries and/or other unanticipated problems involving risk to 
      participants. 
 I am in compliance with the requirements set by the University and qualify to serve as the 
      principal investigator of this project or have acquired the appropriate approval from the  
      Dean’s Office or Office of the Provost, or the Human Subject Protection Administrator at 
      Yale-New Haven Hospital, or have a faculty advisor. 
 I will identify a qualified successor should I cease my role as principal investigator and facilitate a 
smooth transfer of investigator responsibilities. 
____ 
 _   Brett King               9/22/15         
    
   PI Name (PRINT) and Signature                  
Date 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017

Page 7 of 26 
 
 
Department Chair’s Assurance Statement 
Do you know of any real or apparent institutional conflict of interest (e.g., Yale ownership of a 
sponsoring company, patents, licensure) associated with this research project? 
 Yes (provide a description of that interest in a separate letter addressed to the HIC.) 
 No 
 
As Chair, do you have any real or apparent protocol-specific conflict of interest between yourself and 
the sponsor of the research project, or its competitor or any interest in any intervention and/or method 
tested in the project that might compromise this research project? 
Yes (provide a description of that interest in a separate letter addressed to the HIC) 
No 
 
I assure the HIC that the principal investigator and all members of the research team are qualified by 
education, training, licensure and/or experience to assume participation in the conduct of this research 
trial. I also assure that the principal investigator has departmental support and sufficient resources to 
conduct this trial appropriately. 
 
   _________
___________Richard Edelson____          10/2/15     
   Chair Name (PRINT) and Signature                       Date 
 
   ___Dermatology______________________________ 
   Department 
YNHH Human Subjects Protection Administrator Assurance Statement 
Required when the study is conducted solely at YNHH by YNHH health care providers. 
 
As Human Subject Protection Administrator (HSPA) for YNHH, I certify that: 
 I have read a copy of the protocol and approve it being conducted at YNHH. 
 I agree to notify the IRB if I am aware of any real or apparent institutional conflict of interest. 
 The principal investigator of this study is qualified to serve as P.I. and has the support of the hospital 
for this research project. 
 
  ______________________________________                                
    YNHH HSPA Name (PRINT) and Signature                   
Date 
 
 
 
SECTION V: RESEARCH PLAN 
 
1. Statement of Purpose: State the scientific aim(s) of the study, or the hypotheses to be tested.  
 
To investigate the use of topical tofacitinib to promote hair regrowth in patients with alopecia 
areata, alopecia totalis, and alopecia universalis. 
 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017

Page 8 of 26 
 
2. Background: Describe the background information that led to the plan for this project. 
Provide references to support the expectation of obtaining useful scientific data. 
 
Alopecia areata (AA) is a condition characterized by recurrent localized hair loss, usually 
involving the scalp, though other hair-bearing sites may be affected. Two variants of AA, 
alopecia totalis (AT) and alopecia universalis (AU), are characterized by complete loss of scalp 
hair and complete loss of all body hair, respectively. The prevalence of AA is 0.1-0.2%; its 
variants occur less often. The treatment of AA includes steroid injections into the skin at sites of 
involvement as well as topical steroids. When these therapies fail there are few, if any, reliable 
treatment options.  
 
In a murine model of alopecia areata, a Type I cytotoxic pathway has been demonstrated to be 
responsible for the disease state, with NKG2D-expressing CD8+ cytolytic T-lymphocytes 
identified as both necessary and sufficient for induction of disease
1. Upregulation of IL-15 in the 
outer root sheath of the hair follicle activates cytolytic T-lymphocytes, which in turn produce 
IFN, leading to activation of the hair follicle and upregulation of IL-15, NKG2D ligands, and 
MHC molecules, all of which target the hair follicle for attack. Systemic treatment with the JAK 
inhibitors tofacitinib (a JAK 1/3 inhibitor) and ruxolitinib (a JAK 1/2 inhibitor) prevents the 
onset of AA in grafted AA mice, and topical treatment reverses AA in these mice. JAK 1/3 
signaling mediates IL-15 activation of T-lymphocytes, explaining the success of these therapies.  
 
Based on the details above, we treated a single patient with alopecia universalis (and psoriasis) 
with oral tofacitinib, and he experienced complete hair regrowth2. Subsequently, we carried out a 
clinical trial investigating oral tofacitinib for the treatment of AA and its variants in 30 patients 
(Yale HIC # 1407014260  / ClinicalTrials.gov NCT02197455), for which data analysis is 
currently underway. This trial was replicated at Stanford University in 36 patients 
(NCT02312882).  In our clinical practice we have now treated over 100 patients with oral 
tofacitinib.  In addition, we have successfully treated a patient with compounded topical 
ruxolitinib, and she experienced hair regrowth (accepted for publication).  Although rare, there 
are risks for serious adverse effects with systemic therapy that might be avoided if topical 
therapy were an option.  Given this, the use of topical tofacitinib should be evaluated.  
 
3. Research Plan: Summarize the study design and research procedures using non-technical 
language that can be readily understood by someone outside the discipline. Be sure to distinguish 
between standard of care vs. research procedures when applicable, and include any flowcharts of 
visits specifying their individual times and lengths. Describe the setting in which the research 
will take place. 
 
This will be an open label clinical trial. We plan to treat 10 adults with AA (with at least 2 
patches of alopecia involving the scalp), AT or AU with tofacitinib ointment for a maximum of 6 
months. During treatment, patients will be evaluated every 4 weeks and effectiveness of the 
medication will be measured by changes in hair growth. Laboratory evaluation will be performed 
before and during treatment in order to monitor for adverse effects of the medication.     
 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
Study data will be gathered at outpatient clinic visits. Participants enrolled in the study will 
receive up to 90 grams of tofacitinib 2% ointment monthly. In participants with AA, topical 

Page 9 of 26 
 
tofacitinib will be applied to up to half of the alopecic patches (no more than 4 patches). In 
participants with AT or AU, tofacitinib 2% ointment will be applied to half of the scalp. Topical 
tofacitinib will be applied twice daily. Patients will wash their hands prior to and following 
application of the ointment. Patients demonstrating hair regrowth in the tofacitinib application 
sites will subsequently apply tofacitinib ointment to all involved sites when evidence of regrowth 
is observed at the initial sites of application. Treatment will be discontinued when either full 
regrowth has occurred in areas of application or at 6 months of treatment, whichever comes first. 
If a clinically significant adverse effect (lab abnormality or patient-reported adverse effect) is 
encountered, then the application frequency will be decreased to once daily. In the case of a 
serious adverse effect, tofacitinib ointment will be immediately discontinued.  
 
Screening labs will include QuantiFERON® TB gold or PPD, fasting lipid panel, complete 
metabolic panel, and complete blood count with differential. Females of childbearing potential 
will require a negative pregnancy test prior to initiating treatment. While on treatment, 
participants will be evaluated every 4 weeks. Physical exam of the skin with special attention to 
presence or absence of hair growth, photographs of the skin, as well as a complete review of 
systems (headache, dizziness, fever, cough, shortness of breath, nausea, vomiting, diarrhea) will 
be performed at each visit. Severity of Alopecia Tool (SALT) will be used to score alopecia 
severity prior to and at the end of treatment, and the change in SALT score will be measured. 
Visits will take place at Yale Dermatology – Middlebury or Yale Dermatology Associates. 
Patients will be evaluated monthly for a maximum of 6 months. As above, patients who 
experience complete hair growth prior to 6 months will discontinue therapy at the visit when full 
hair growth has occurred.  Labs will be monitored at 1 month and at completion of therapy, 
which for most patients will be after 6 months of treatment, and will include fasting lipid panel, 
complete blood count with differential, and complete metabolic panel.  This will require 2-3 vials 
or approximately 6-12 mL of blood at each blood draw). 
 
 
3. Genetic Testing    
N/A    
A. Describe 
i. the types of future research to be conducted using the materials, specifying if 
immortalization of cell lines, whole exome or genome sequencing, genome wide 
association studies, or animal studies are planned 
ii. the plan for the collection of material or the conditions under which material will 
be received 
iii. the types of information about the donor/individual contributors that will be 
entered into a database 
iv. the methods to uphold confidentiality 
 
B. What are the conditions or procedures for sharing of materials and/or distributing for 
future research projects? 
C. Is widespread sharing of materials planned? 
D. When and under what conditions will materials be stripped of all identifiers? 
E. 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
Can donor-subjects withdraw their materials at any time, and/or withdraw the identifiers 
that connect them to their materials? 

Page 10 of 26 
 
i. How will requests to withdraw materials be handled (e.g., material no longer 
identified: that is, anonymized) or material destroyed)? 
 
F. Describe the provisions for protection of participant privacy 
G. Describe the methods for the security of storage and sharing of materials  
 
 
4. Subject Population: Provide a detailed description of the types of human subjects who will 
be recruited into this study. 
 
A total of 10 participants, 18 years of age or older will be enrolled.  Participants must have a 
diagnosis of AA, AT or AU.  
 
5. Subject classification: Check off all classifications of subjects that will be specifically 
recruited for enrollment in the research project. Will subjects who may require additional 
safeguards or other considerations be enrolled in the study? If so, identify the population of 
subjects requiring special safeguards and provide a justification for their involvement. 
 
 Children         
 Healthy      
Fetal material, placenta, or dead fetus 
 Non-English Speaking    Prisoners     
 Economically disadvantaged persons 
 Decisionally Impaired    Employees 
   
 Pregnant women and/or fetuses 
 Yale Students       
Females of childbearing potential 
 
NOTE: Is this research proposal designed to enroll children who are wards of the state as 
potential subjects?   Yes     No (If yes, see Instructions section VII #4 for further 
requirements) 
 
 
6. Inclusion/Exclusion Criteria: What are the criteria used to determine subject inclusion or    
exclusion? 
 
Patients will be included in the study if all of the following conditions are met: 
• Age ≥ 18-years old 
• Diagnosis of AA with at least 2 patches of alopecia involving the scalp, AT or AU 
• Stable hair loss present for 6 months or longer  
• No treatment for alopecia areata in the past 1 month  
• No evidence of spontaneous hair regrowth  
 
Patients will be excluded from the study if any of the following conditions are met: 
• Age <18 years old 
• Patients have received treatment known to affect alopecia areata within 1 month of 
enrolling in the study  
• Patients whose current episode of AT or AU is more than 5 years  
• Patients with a history of malignancy (except history of successfully treated basal cell or 
squamous cell carcinoma of the skin) 
• 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
Patients known to be HIV or hepatitis B or C positive  

Page 11 of 26 
 
• Patients with positive tuberculin skin test or positive QuantiFERON® TB test 
• Patients with leukopenia or anemia 
• Patients with renal or hepatic impairment 
• Patients taking immunosuppressive medications, including but not limited to prednisone, 
methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or TNF-α 
inhibitors 
• Women who are pregnant or nursing 
 
7. How will eligibility be determined, and by whom? 
 
Eligibility will be determined by the PI, Brett King, MD, PhD and/or co-investigator Brittany 
Craiglow, MD. Patients will be evaluated in person at a regular clinic appointment to 
determine if they meet inclusion criteria.  
 
8. Risks: Describe the reasonably foreseeable risks, including risks to subject privacy, 
discomforts, or inconveniences associated with subjects participating in the research.  
 
The risks associated with oral tofacitinib are listed below:  
• Infections, including severe and opportunistic infections 
• Viral reactivation  
• Neutropenia 
• Lymphopenia 
• Anemia 
• Malignancy  
• Lymphoma 
• Gastrointestinal perforation  
• Headache 
• Diarrhea 
• Increased liver transaminases 
• Increased creatinine 
• Increased cholesterol  
 
The above risks are very unlikely likely to occur with topical administration given what is 
known about transepidermal absorption and minimal surface area of application in this 
trial.  Therefore, the only reasonably foreseeable risk is irritation at the site of application. 
There are no other known risks to the study.  
 
9. Minimizing Risks: Describe the manner in which the above-mentioned risks will be 
minimized. 
 
Screening visit will allow for exclusion of patients who do not meet inclusion criteria. 
Maximum time on treatment will be 6 months. Patients will undergo clinical evaluation every 
month during treatment and labs will be monitored at 1 and 6 months of treatment.  Surface 
area of application will be limited to the scalp.  
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 

Page 12 of 26 
 
10. Data and Safety Monitoring Plan: Include an appropriate Data and Safety Monitoring Plan 
(DSMP) based on the investigator’s risk assessment stated below. (Note: the HIC will make 
the final determination of the risk to subjects.) For more information, see the Instructions, 
page 24. 
   
a.    What is the investigator’s assessment of the overall risk level for subjects 
participating in this study?  Minimal risk 
b.    If children are involved, what is the investigator’s assessment of the overall risk 
level for the children participating in this study?  N/A 
c.    Copy, paste, and then tailor an appropriate Data and Safety Monitoring Plan  
from  http://www.yale.edu/hrpp/forms-templates/biomedical.html  for 
i. Minimal risk 
ii. Greater than minimal/moderate risk 
iii. High risk 
 
Minimal Risk DSMP 
 
The principal investigator is responsible for monitoring the data, assuring protocol compliance, 
and conducting the safety reviews monthly.  During the review process the principal investigator 
will evaluate whether the study should continue unchanged, require modification/amendment, or 
close to enrollment. 
 
The principal investigator (monitor) or the Institutional Review Board (IRB) have the authority 
to stop or suspend the study or require modifications. 
 
This protocol presents minimal risks to the subjects and Unanticipated Problems Involving Risks 
to Subjects or Others (UPIRSOs), including adverse events, are not anticipated. In the unlikely 
event that such events occur, Reportable Events (which are events that are serious or life-
threatening and unanticipated (or anticipated but occurring with a greater frequency than 
expected) and possibly, probably, or definitely related) or Unanticipated Problems Involving 
Risks to Subjects or Others that may require a temporary or permanent interruption of study 
activities will be reported immediately (if possible), followed by a written report within 5 
calendar days of the Principal Investigator becoming aware of the event to the IRB (using the 
appropriate forms from the website) and any appropriate funding and regulatory agencies. The 
investigator will apprise fellow investigators and study personnel of all UPIRSOs and adverse 
events that occur during the conduct of this research project as they are reviewed by the principal 
investigator. The protocol’s research monitor, co-investigators and Pfizer will be informed of 
adverse events within 5 days of the event becoming known to the principal investigator. 
 
 
11. Statistical Considerations: Describe the statistical analyses that support the study design.  
 
This will be a pilot study that will be primarily observational in nature, and statistics will be 
purely descriptive. Pre-and post-treatment SALT scores will be compared for individual patients, 
and the mean change in score values from baseline will be described. Clinical photographs will 
be used to demonstrate presence or absence of hair regrowth.   
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 

Page 13 of 26 
 
 
 
 
SECTION VI: RESEARCH INVOLVING DRUGS,
 BIOLOGICS,
 RADIOTRACERS,
 PLACEBOS AND 
DEVICES 
 
   
If this section (or one of its parts, A or B) is not applicable, state N/A and delete the rest of the 
section. 
 
A.  DRUGS, BIOLOGICS and RADIOTRACERS 
 
1. Identification of Drug, Biologic or Radiotracer: What is (are) the name(s) of the drug(s)  
biologic(s) or radiotracer(s) being used? Identify whether FDA approval has been granted and for what 
indication(s).  
 
Topical tofacitinib ointment has been studied for the treatment of psoriasis and atopic dermatitis 
(phase II trials) but is not currently FDA-approved.  The oral form of tofacitinib citrate is FDA-
approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) who 
have had an inadequate response to, or who are intolerant of, methotrexate. 
 
 
All protocols which utilize a drug, biologic or radiotracer not approved by, but regulated by, the FDA, 
or a radiotracer regulated by the RDRC, must provide the following information:    
 Not applicable to this research project. 
 
a. What is the Investigational New Drug (IND) number assigned by the FDA? 203214 
b. Who holds the IND? Pfizer 
c. All protocols which utilize a radiotracer not approved by, but regulated by the FDA must 
provide the IND number: _______________ 
Alternatively, use of the investigational radiotracer may be under RDRC/RSC oversight: (check 
if appropriate)_____________ 
 
For all investigational radiotracers, attach a copy of the RDRC/RSC application (for 
radioisotopes used in the PET Center, PET Center personnel may complete this step) 
Go to http://rsc.med.yale.edu/login.asp?url=myApps.asp.  When you have logged in, complete 
the application and attach a copy to this submission.      
 
Alternatively, an exemption from IND filing requirements may be sought for a clinical 
 investigation of a drug product that is lawfully marketed in the United States. If there is no IND and 
 an exemption is being sought, review the following categories and complete the category that applies 
 (and delete the inapplicable categories): 
 
Exempt Category 1 
The clinical investigation of a drug product that is lawfully marketed in the United States can be 
exempt from IND regulations if all of the following are yes: 
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Page 14 of 26 
 
i.   The intention of the investigation is NOT to report to the FDA as a well-controlled study in support 
     of a new indication for use or to be used to support any other significant change in the labeling for 
     the drug.    Yes     No 
ii. The drug that is undergoing investigation is lawfully marketed as a prescription drug product, and 
      the intention of the investigation is NOT to support a significant change in the advertising for the 
      product.   Yes     No 
iii.  The investigation does NOT involve a route of administration or dosage level or use in populations 
      or other factor that significantly increases the risks (or decreases the acceptability of the risks)    
      associated with the use of the drug product.   Yes     No 
iv. The investigation will be conducted in compliance with the requirements for institutional (HIC)    
      review and with the requirements for informed consent of the FDA regulations (21 CFR Part 50  
and 21 CFR Part 56).   Yes     No 
v.   The investigation will be conducted in compliance with the requirements regarding promotion and 
charging for investigational drugs.   Yes     No 
 
 
2.  Background Information: Provide a description of previous human use, known risks, and data 
addressing dosage(s), interval(s), route(s) of administration, and any other factors that might 
influence risks. If this is the first time this drug is being administered to humans, include relevant 
data on animal models.  
 
Oral tofacitinib was approved by the FDA in 2012 for the treatment of moderate to severe 
rheumatoid arthritis (RA) who have had an inadequate response to, or who are intolerant of, 
methotrexate.  It is likely to be approved by the FDA in the next 4-8 weeks for the treatment of 
psoriasis.  Its use is currently being studied in a variety of other inflammatory diseases, including 
psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis, Crohn’s disease, and 
ulcerative colitis (clinicaltrials.gov).  
 
Topical tofacitinib 2% ointment has been demonstrated to be well-tolerated and effective for the 
treatment of plaque psoriasis.
3   It has also been studied in a phase II trial for atopic dermatitis 
(results not yet published). 
The following table presents the risks as summarized in the package insert for oral XELJANZ.  
As mentioned above, the risks are likely to be far lower or nonexistent with topical 
administration because of minimal transepidermal absorption and the limited surface area 
of application being proposed in this study.   As stated in Pfizer’s investigator brochure, based 
on in vitro data, systemic bioavailability is predicted to be low (≤3%) following topical dosing 
relative to the oral route of administration. 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 

Page 15 of 26 
 
Table 1: Adverse Effects with the use of oral tofacitinib citrate. The following data includes two phase 2 and five phase 3 double-
blind, controlled, multicenter trials. In these trials, patients were randomized to doses of XELJANZ 5 mg twice daily (292 patients) 
and 10 mg twice daily (306 patients) monotherapy, XELJANZ 5 mg twice daily (1044 patients) and 10 mg twice daily (1043 patients) 
in combination with DMARDs (including methotrexate) and placebo (809 patients). All seven protocols included provisions for 
patients taking placebo to receive treatment with XELJANZ at Month 3 or Month 6 either by patient response (based on uncontrolled 
disease activity) or by design, so that adverse events cannot always be unambiguously attributed to a given treatment. Comparisons 
between placebo and XELJANZ were based on the first 3 months of exposure, and comparisons between XELJANZ 5 mg twice daily 
and XELJANZ 10 mg twice daily were based on the first 12 months of exposure. 
Adverse effect 
Tofacitinib citrate: 
5 mg twice daily 
Tofacitinib citrate: 
10 mg twice daily 
Placebo   
Notes: 
Percentage of patients with 
any adverse effect requiring 
discontinuation of therapy.  
4% 
4% 
3%   
Any adverse reaction during the 0-3 months exposure in the 
double-blind, placebo-controlled trials. 
Overall infection:  
20%  
22% 
18%   
Most common reported infections were URI, 
nasopharyngitis and UTI with a rate of 4%, 3% and 2%, 
respectively. 
 
Serious infection: 0-3 
months of therapy.  
11 patients (1.7 
events per 100 
patient-years) 
11 patients (1.7 
events per 100 
patient-years) 
1 patient (0.5 
events per 100 
patient-years) 
Most common serious infections included pneumonia, 
cellulitis, herpes zoster and UTI. 
 
The rate difference between treatment groups (and the 
corresponding 95% confidence interval) was 1.1 (-0.4, 2.5) 
events per 100 patient-years for the combined 5 mg twice 
daily and 10 mg twice daily tofacitinib group minus placebo. 
 
Serious infection: 0-12 
months of therapy.  
34 patients (2.7 
events per 100 
patient-years) 
33 patients (2.7 
events per 100 
patient-years) 
N/A   
Most common serious infections included pneumonia, 
cellulitis, herpes zoster and UTI. 
 
The rate difference between tofacitinib doses (and the 
corresponding 95% confidence interval) was -0.1 (-1.3, 1.2) 
events per 100 patient-years for 10 mg twice daily tofacitinib 
minus 5 mg twice daily tofacitinib. 
Tuberculosis: 0-3 months 
of therapy 
0 
0 
0 
During the 0 to 3 months exposure, tuberculosis was not 
reported in patients who received placebo, 5 mg twice daily 
of tofacitinib, or 10 mg twice daily of tofacitinib. 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017

Page 16 of 26 
 
Tuberculosis: 0-12 months 
of therapy 
0 
6 (0.5 events per 
100 patient-years) 
N/A   
The rate difference between tofacitinib doses (and the 
corresponding 95% confidence interval) was 0.5 (0.1, 0.9) 
events per 100 patient-years for 10 mg twice daily tofacitinib 
minus 5 mg twice daily tofacitinib. 
Cases of disseminated tuberculosis were also reported. The 
median tofacitinib exposure prior to diagnosis of 
tuberculosis was 10 months (range from 152 to 960 days). 
Opportunistic infections 
(excluding tuberculosis): 
0-3 months of therapy 
0 
0 
0 
In the seven controlled trials, during the 0 to 3 months 
exposure, opportunistic infections were not reported in 
patients who received placebo, 5 mg twice daily of 
tofacitinib, or 10 mg twice daily of tofacitinib. 
Opportunistic infections 
(excluding tuberculosis): 
0-12 months of therapy 
4 (0.3 events per 
100 patient-years) 
4 (0.3 events per 
100 patient-years) 
N/A   
The rate difference between tofacitinib doses (and the 
corresponding 95% confidence interval) was 0 (-0.5, 0.5) 
events per 100 patient-years for 10 mg twice daily tofacitinib 
minus 5 mg twice daily tofacitinib. 
Malignancy: 0-3 months of 
therapy.  
2 patients (0.3 
events per 100 
patient-years) 
2 patients (0.3 
events per 100 
patient-years) 
0 
Most common types of malignancy were lung and breast 
cancer, followed by gastric, colorectal, renal cell, prostate 
cancer, lymphoma and malignant melanoma. 
The rate difference between treatment groups (and the 
corresponding 95% confidence interval) was 0.3 (-0.1, 0.7) 
events per 100 patient-years for the combined 5 mg and 10 
mg twice daily tofacitinib group minus placebo. 
Malignancy: 0-12 months 
of therapy 
5 patients (0.4 
events per 100 
patient-years) 
7 patients (0.6 
events per 100 
patient-years) 
N/A   
One of these malignancies was a case of lymphoma that 
occurred during the 0 to 12 month period in a patient treated 
with tofacitinib 10 mg twice daily. 
The rate difference between tofacitinib doses (and the 
corresponding 95% confidence interval) was 0.2 (-0.4, 0.7) 
events per 100 patient-years for 10 mg twice daily tofacitinib 
minus 5 mg twice daily tofacitinib.  
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017

Page 17 of 26 
 
Lymphopenia: confirmed 
decreases in absolute 
lymphocyte counts below 
500 cells/mm3. 
0.04% 
0.04% 
N/A   
Confirmed lymphocyte counts less than 500 cells/mm3 were 
associated with an increased incidence of treated and serious 
infections. 
Neutropenia: ANC below 
1,000 cells/mm3.  
0.07% 
0.07% 
N/A   
There were no ANC below 500 cells/mm3 observed in any 
treatment group. There was no clear relationship between 
neutropenia and the occurrence of serious infections. 
Liver enzyme elevations: 
percentage of patients with 
ALT elevations >3x ULN 
on DMARD trials.  
1.3% 
1.2% 
1.0%   
No elevations of liver enzymes were seen in controlled 
monotherapy with tofacitinib. 
Liver enzyme elevations: 
percentage of patients with 
AST elevations >3x ULN on 
DMARD trials.  
0.5% 
0.4% 
0.6%   
No elevations of liver enzymes were seen in controlled 
monotherapy with tofacitinib. 
Lipid elevations: Mean 
LDL cholesterol 
Increased by 15%   Increased by 19%   N/A   
Dose-related elevations in lipid parameters (total cholesterol, 
LDL cholesterol, HDL cholesterol, triglycerides) were 
observed at one month of exposure and remained stable 
thereafter. 
 
Lipid elevations: Mean 
HDL cholesterol 
Increased by 10%   Increased by 12%   N/A   
Dose-related elevations in lipid parameters (total cholesterol, 
LDL cholesterol, HDL cholesterol, triglycerides) were 
observed at one month of exposure and remained stable 
thereafter. 
 
Lipid elevations: Mean 
LDL/HDL ratios 
Unchanged   
Unchanged   
N/A   
 
Serum creatinine 
elevations:  
Mean increase in 
serum creatinine 
was < 0.1 mg/dL 
Mean increase in 
serum creatinine 
was < 0.1 mg/dL 
 
Dose-related elevations in serum creatinine were observed 
with tofacitinib treatment. 
Up to 2% of patients were discontinued from tofacitinib 
treatment due to the protocol-specified discontinuation 
criterion of an increase in creatinine by more than 50% of 
baseline. The clinical significance of the observed serum 
creatinine elevations is unknown. 
 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
ANC: absolute neutrophil count, DMARD: disease-modifying anti-rheumatic drug, ULN: upper limit of normal, URI: upper 
respiratory infection, UTI: urinary tract infection 

Page 18 of 26 
 
 
3.  Source:  a) Identify the source of the drug or biologic to be used.  
            
Pfizer Pharmaceuticals  
         b) Is the drug provided free of charge to subjects?   Yes     No 
             If yes, by whom?  Pfizer 
 
4.  Storage, Preparation and Use: Describe the method of storage, preparation, stability information, 
and for parenteral products, method of sterilization and method of testing sterility and 
pyrogenicity.  
  Check applicable Investigational Drug Service utilized: 
         YNHH IDS                                                                          Yale Cancer Center  
         CMHC Pharmacy                                                             West Haven VA 
         PET Center                                                                         None      N/A 
          Other:  
Note: If the YNHH IDS (or comparable service at CMHC or WHVA) will not be utilized, explain in 
detail how the PI will oversee these aspects of drug accountability, storage, and preparation.   
    
 
5.  Use of Placebo:    Not applicable to this research project 
   If use of a placebo is planned, provide a justification which addresses the following: 
a. Describe the safety and efficacy of other available therapies. If there are no other 
available therapies, state this. 
  b.   State the maximum total length of time a participant may receive placebo while on the study.  
  c.   Address the greatest potential harm that may come to a participant as a result of  receiving     
         placebo.  
  d.   Describe the procedures that are in place to safeguard participants receiving placebo.  
 
6. Use of Controlled Substances: 
   Will this research project involve the use of controlled substances in human subjects? 
    Yes     No  See HIC Application Instructions to view controlled substance listings.  
 
   If yes, is the use of the controlled substance considered: 
    Therapeutic: The use of the controlled substance, within the context of the research, has the 
potential to benefit the research participant. 
    Non-Therapeutic: Note, the use of a controlled substance in a non-therapeutic research study 
involving human subjects may require that the investigator obtain a Laboratory Research License. 
Examples include controlled substances used for basic imaging, observation or biochemical 
studies or other non-therapeutic purposes. See Instructions for further information. 
 
7. Continuation of Drug Therapy After Study Closure      Not applicable to this project 
   Are subjects provided the opportunity to continue to receive the study drug(s) after the study has 
ended? 
   Yes   If yes, describe the conditions under which continued access to study drug(s) may apply 
as well as conditions for termination of such access.  
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
Patients who experience hair regrowth that is not durable after study completion may elect to 
restart the medication.  

Page 19 of 26 
 
 
      No    If no, explain why this is acceptable. 
The drug will be provided by Pfizer for the duration of the study only.   
 
 B.  DEVICES 
N/A 
SECTION VII: RECRUITMENT/
CONSENT AND ASSENT PROCEDURES  
1. Targeted Enrollment: Give the number of subjects: 
a.   targeted for enrollment at Yale for this protocol: 10 
b.    If this is a multi-site study, give the total number of subjects targeted across all 
sites___  
 
2. Indicate recruitment methods below.  Attach copies of any recruitment materials that will be used. 
 
 Flyers                  
 Internet/Web Postings          
 Radio 
 Posters                 
 Mass E-mail Solicitation         
 Telephone 
 Letter                   
 Departmental/Center Website      
 Television 
 Medical Record Review 
       
 Departmental/Center Research Boards    Newspaper 
 Departmental/Center Newsletters   
 Web-Based Clinical Trial Registries     
  YCCI Recruitment database     
 Clinicaltrials.gov Registry (do not send materials to 
HIC) 
 Other (describe): outpatient clinic (see Recruitment Procedures below) 
 
3.  Recruitment Procedures:  
a. Describe how potential subjects will be identified.  
Dr. King and Dr. Craiglow see 5-10 new patients and 10-20 established patients 
with AA, AT or AU every month their clinics at Yale Dermatology  
b. Describe how potential subjects are contacted.  
At the time of their routine appointment with Dr. King or Dr. Craiglow patients 
will be told of the study. 
c. Who is recruiting potential subjects?  
Patients will be recruited from the clinical practice of Dr. Brett King and Dr. 
Brittany Craiglow.  
    
 
4. Screening Procedures 
a. Will email or telephone correspondence be used to screen potential subjects for 
eligibility prior to the potential subject coming to the research office?   Yes     No 
b.  If yes, identify below all health information to be collected as part of screening and 
check off any of the following HIPAA identifiers to be collected and retained by the 
research team during this screening process.  
 
 
HEALTH INFORMATION TO BE COLLECTED: 
 
HIPAA identifiers:  
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 Names  

Page 20 of 26 
 
 All geographic subdivisions smaller than a State, including: street address, city, county, precinct, 
zip codes and their equivalent geocodes, except for the initial three digits of a zip code if, according to 
the current publicly-available data from the Bureau of the Census: (1) the geographic unit formed by 
combining all zip codes with the same three initial digits contains more than 20,000 people, and (2) the 
initial  
three  digits  of  a  zip  code  
for  all  such  geographic  units  containing  20,000  or  
fewer  people  
is 
changed to 000.  
 Telephone numbers 
 Fax numbers  
 E-mail addresses 
 Social Security numbers  
 Medical record numbers 
 Health plan beneficiary numbers  
 Account numbers  
 All  elements  of  dates  (except  year)  for  dates  related  to  an  individual,  including:  birth  date, 
admission  date,  discharge  date,  date  of  death,  all  ages  over  89  and  all  elements  of  dates  
(including 
year)  indicative  of  such  age,  except  that  such  ages  and  elements  may  be  aggregated  into  a  single 
category of age 90 or older  
 Certificate/license numbers  
 Vehicle identifiers and serial numbers, including license plate numbers  
 Device identifiers and serial numbers  
 Web Universal Resource Locators (URLs)  
 Internet Protocol (IP) address numbers  
 Biometric identifiers, including finger and voice prints  
 Full face photographic images and any comparable images  
 Any other unique identifying numbers, characteristics, or codes  
 
 
5. Assessment of Current Health Provider Relationship for HIPAA Consideration: 
Does the Investigator or any member of the research team have a direct existing clinical 
relationship with any potential subject?  
 Yes, all subjects 
 Yes, some of the subjects. Some patients may be existing patients, while others will be new 
patients.  
 No 
 
If yes, describe the nature of this relationship. 
 
    
Doctor-patient relationship (established patients in our clinics).  
 
 
6. Request for waiver of HIPAA authorization: (When requesting a waiver of HIPAA Authorization 
for either the entire study, or for recruitment purposes only.  Note: if you are collecting PHI as part of 
a phone or email screen, you must request a HIPAA waiver for recruitment purposes.) 
 
Choose one: 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
For entire study: ______ For recruitment purposes only: ______ 

Page 21 of 26 
 
i. Describe why it would be impracticable to obtain the subject’s authorization for 
use/disclosure of this data; 
ii. If requesting a waiver of signed authorization, describe why it would be 
impracticable to obtain the subject’s signed authorization for use/disclosure of this 
data; 
 
By signing this protocol application, the investigator assures that the protected 
health information for which a Waiver of Authorization has been requested will not 
be reused or disclosed to any person or entity other than those listed in this 
application, except as required by law, for authorized oversight of this research 
study, or as specifically approved for use in another study by an IRB. 
 
Researchers are reminded that unauthorized disclosures of PHI to individuals outside of the Yale 
HIPAA-Covered entity must be accounted for in the “accounting for disclosures log”, by subject 
name, purpose, date, recipients, and a description of information provided.  Logs are to be 
forwarded to the Deputy HIPAA Privacy Officer. 
 
7. Required HIPAA Authorization: If the research involves the creation, use or disclosure of 
protected health information (PHI), separate subject authorization is required under the 
HIPAA Privacy Rule. Indicate which of the following forms are being provided: 
        
 Compound Consent and Authorization form 
        
 HIPAA Research Authorization Form 
    
8. Consent Personnel: List the names of all members of the research team who will be obtaining 
consent/assent.  
 
Brett King, MD, PhD; Brittany Craiglow, MD 
 
 
9. Process of Consent/Assent: Describe the setting and conditions under which consent/assent will 
be obtained, including parental permission or surrogate permission and the steps taken to ensure 
subjects’ independent decision-making.  
 
The patient will be offered participation in the study during an outpatient visit to either Dr. Brett 
King or Dr. Brittany Craiglow. The project description, known risks of the research drug, etc. are 
detailed in the consent form and will be discussed with potential study participants.  
 
 
10. Evaluation of Subject(s) Capacity to Provide Informed Consent/Assent: Indicate how the 
personnel obtaining consent will assess the potential subject’s ability and capacity to consent to the 
research being proposed.  
 
Study subjects will be considered to have capacity to provide informed consent if they provide 
comprehensible and sensible answers to the following questions: 
(1) Tell me what will happen if you agree to partake in this study? 
(2) 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
Can you leave this study once it begins? 

Page 22 of 26 
 
(3) What should you do if you want to stop being in this study? 
 
 
11. Documentation of Consent/Assent: The attached consent form will be used to obtain consent.  
 
 
12. Non-English Speaking Subjects: Explain provisions in place to ensure comprehension for 
research involving non-English speaking subjects. Translated copies of all consent materials must 
be submitted for approval prior to use.  
 
None will be included in this study.  
 
13. Consent Waiver: In certain circumstances, the HIC may grant a waiver of signed consent, or 
a full waiver of consent, depending on the study. If you will request either a waiver of consent, 
or a waiver of signed consent for this study, complete the appropriate section below.   
   Not Requesting a consent waiver  
   Requesting a waiver of signed consent 
         Requesting a full waiver of consent 
    
 
A. Waiver of signed consent: (Verbal consent from subjects will be obtained. If PHI is 
collected, information in this section must match Section VII, Question 6) 
 Requesting a waiver of signed consent for Recruitment/Screening only  
If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes     No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes     No 
 
               
OR 
 
c. Does the research activity pose greater than minimal risk?  
 Yes If you answered yes, stop. A waiver cannot be granted.  Please note: 
Recruitment/screening is generally a minimal risk research activity   
 No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context?   Yes    No 
 
 Requesting a waiver of signed consent for the Entire Study (Note that an information 
sheet may be required.) 
         If requesting a waiver of signed consent, please address the following: 
a. Would the signed consent form be the only record linking the subject and the research? 
 Yes     No 
b. Does a breach of confidentiality constitute the principal risk to subjects?  
 Yes  
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
 No 

Page 23 of 26 
 
 
               
OR 
 
c. Does the research pose greater than minimal risk?   Yes If you answered yes, stop. A 
waiver cannot be granted.      No  
AND 
d. Does the research include any activities that would require signed consent in a non-
research context?   Yes     No 
     
 B. Full waiver of consent: (No consent from subjects will be obtained for the activity.)  
 Requesting a waiver of consent for Recruitment/Screening only  
a. Does the research activity pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted. Please note: 
Recruitment/screening is generally a minimal risk research activity  
 No 
        b. Will the waiver adversely affect subjects’ rights and welfare?   Yes     No 
         c. Why would the research be impracticable to conduct without the waiver?  
   d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
 
 Requesting a full waiver of consent for the Entire Study (Note: If PHI is 
collected, information here must match Section VII, question 6.) 
          
If requesting a full waiver of consent, please address the following: 
 
         a. Does the research pose greater than minimal risk to subjects?   
 Yes  If you answered yes, stop. A waiver cannot be granted.   
 No 
        b. Will the waiver adversely affect subjects’ rights and welfare?   Yes     No 
         c. Why would the research be impracticable to conduct without the waiver?  
   d. Where appropriate, how will pertinent information be returned to, or shared with 
subjects at a later date?  
 
SECTION VIII: PROTECTION OF RESEARCH SUBJECTS 
 
    Confidentiality & Security of Data: 
a.    What protected health information (medical information along with the HIPAA identifiers) 
about subjects will be collected and used for the research?    
 
Name, age, gender, race, age of onset of alopecia areata and subsequent natural history 
(including episodes of regrowth and recurrence), prior therapies, comorbid conditions, percent 
scalp involvement of hair loss at initial presentation and follow-up visits (as measured via 
Severity of Alopecia Tool – SALT score), involvement of eyebrows, eyelashes and body hair, 
treatment including dose and duration, response to treatment, adverse effects 
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Page 24 of 26 
 
        
b.    How will the research data be collected, recorded and stored? Laptop 1 with patient data in 
an Excel spreadsheet with a code identifier for each patient. The code identifiers will be stored 
separately  on a  different laptop  computer.  The  laptops  are  encrypted  with  Yale  security 
software.  
c.    How will the digital data be stored?    CD     DVD     Flash Drive     Portable Hard    
       Drive     Secured Server     Laptop Computer    Desktop Computer    Other 
d.    What methods and procedures will be used to safeguard the confidentiality and security of     
the identifiable  study  data  and  the  storage  media  indicated  above  during  and  after  the 
subject’s participation in the study? 
Study  participants  will  be  identified  with  a  code  number.  Codes  will  be  maintained  in  a 
separate file.  All data will be kept in password-protected files on an encrypted Yale laptop.   
Do all portable devices contain encryption software?    Yes      No 
         If no, see http://hipaa.yale.edu/guidance/policy.html 
  
e. What will be done with the data when the research is completed? Are there plans to destroy     
the identifiable data? If yes, describe how, by whom and when identifiers will be destroyed. 
If no, describe how the data and/or identifiers will be secured.  
 
Code identifiers will be destroyed by Dr. Brett King by deleting the file so that the data is de-
identified..The de-identified data will be kept for two years.  
 
f.   Who will have access to the protected health information (such as the research sponsor, the  
investigator, the research staff, all research monitors, FDA, Yale Cancer Center Data and Safety 
Monitoring Committee (DSMC), SSC, etc.)? (please distinguish between PHI and de-identified 
data)  
 
Dr. Brett King, Dr. Brittany Craiglow, Lucy Liu, YSM3, Yale Human Investigation Committee, 
Pfizer, Food and Drug Administration 
 
g.   If appropriate, has a Certificate of Confidentiality been obtained? No 
h.   Are any of the study procedures likely to  yield information subject to mandatory reporting   
requirements?  (e.g.  HIV  testing – reporting  of  communicable  diseases;  parent  interview -
incidents of child abuse, elderly abuse, etc.). Please verify to whom such instances will need to 
be reported.  
 
Yes; participants will be screened for TB, HIV and hepatitis B and C. Those found positive will 
be  notified  in  person and will be  reported  to  Connecticut’s  Department  of  Public  Health  per 
mandatory reporting requirements. 
 
 
 
SECTION IX: POTENTIAL BENEFITS 
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Page 25 of 26 
 
   Potential Benefits: Identify any benefits that may be reasonably expected to result from the 
research, either to the subject(s) or to society at large. (Payment of subjects is not considered a 
benefit in this context of the risk benefit assessment.)  
 
The benefits include regrowth of hair. The results of this study may serve as a proof-of-concept 
for the use of topical tofacitinib or other JAK inhibitors in the treatment of AA and its variants.  
 
         S
ECTION X: RESEARCH ALTERNATIVES AND ECONOMIC CONSIDERATIONS 
 
1.     Alternatives: What other alternatives are available to the study subjects outside of the research? 
 
Alternatives include any and all therapeutic interventions offered them by their dermatologist 
(determined by their dermatologist prior to study enrollment) including but not limited to the 
following: 
 Immunosuppressive therapy (e.g. prednisone, cyclosporine) 
 Intralesional corticosteroids 
 Topical contact sensitization therapy (e.g. anthralin, squaric acid 
dibutylester) 
 Topical corticosteroids 
 No treatment  
 
2.   Payments for Participation (Economic Considerations): Describe any payments that will be 
made to subjects, the amount and schedule of payments, and the conditions for receiving this 
compensation.  
 
    No payment for participation will be made.  
 
3.   Costs for Participation (Economic Considerations): Clearly describe the subject’s costs 
associated with participation in the research, and the interventions or procedures of the study that 
will be provided at no cost to subjects.    
       
   There will be no cost to patients to participate in the study.  
 
4.   In Case of Injury: This section is required for any research involving more than minimal risk. 
   a.     Will medical treatment be available if research-related injury occurs? Yes. 
    b.     Where and from whom may treatment be obtained? From appropriate staff at YNHH. 
   c.     Are there any limits to the treatment being provided? No. 
    d.     Who will pay for this treatment? The patient or the patient’s insurance company. 
   e.     How will the medical treatment be accessed by subjects? Treatment may be provided in the 
YNHH outpatient dermatology office or the emergency room if more urgent treatment is 
necessary.  
 
 
 
References: 
APPROVED BY THE YALE UNIVERSITY HIC ON 11 MARCH 2016 VALID THROUGH 12 JANUARY 2017
1.  Xing L, Dai Z, Jabbari A, et al. Alopecia areata is driven by cytotoxic T lymphocytes and is 

Page 26 of 26 
 
reversed by JAK inhibition. Nature medicine. Sep 2014;20(9):1043-1049. 
 
2.   Craiglow BG, King BA. Killing two birds with one stone: oral tofacitinib reverses alopecia 
universalis in a patient with plaque psoriasis. J Invest Dermatol. Dec 2014;134(12):2988-2990. 
 
3. Ports WC, Khan S, Lan S, et al. A randomized phase 2a efficacy and safety trial of the topical 
Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis. Br J Dermatol. Jul  
2013;169(1):137-145. 
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