Conditions: Cutaneous Lupus
Keywords: Systematic Lupus Erythematosus Lupus Systemic Lupus Cutaneous Lupus Tofacitinib Ultraviolet
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 7
Healthy volunteers: no

Brief summary:
This is a single-arm, multi-site, proof-of-concept study that will evaluate the treatment of 10 participants with cutaneous lupus erythematosus (CLE) with Tofacitinib.

Detailed description:
Once consented, study participants meeting all entry criteria will undergo 25 days of treatment with tofacitinib (11 mg orally daily). Tofacitinib will be distributed to eligible participants at Visit 2 (Day 1) and the first dose will be taken on Day 2. The last dose is the morning of Visit 5 (Day 26).Ultraviolet B (UVB)-mediated cutaneous apoptosis and ancillary mechanistic studies will be evaluated in phototests, skin biopsies and blood samples collected before and after treatment.

This study will assess whether a 25-day regimen of tofacitinib impacts photosensitivity following UVB exposure in individuals with CLE.

Arms:
arm 1: 10 participants receiving 11 mg of Tofacitinib administered orally and daily, from Day 2 to Day 26

Interventions: intervention 1: Tofacitinib
Intervention descriptions: intervention 1: 10 participants with Cutaneous lupus erythematosus (CLE). Consenting individuals meeting all entry criteria will undergo 25 days of treatment with tofacitinib (11 mg orally (PO) daily) with evaluation of UVB-mediated cutaneous apoptosis

Protocol document:
Prot_SAP_003.pdf: 




Autoimmunity Centers of Excellence 
Confidential 
Page 3 of 52 
ALE11 
Version 7.0 
October 25, 2023 
Protocol Synopsis 
Title
Evaluation of Tofacitinib in Prevention of Photosensitivity in Cutaneous 
Lupus Erythematosus 
Clinical Phase
Phase I
Number of Sites
1-3
Sponsor/IND Number
DAIT/NIAID, NIH/IND #154164, IND-Exempt
Study Objectives
Primary Objective
1. To determine whether a 25-day regimen of tofacitinib impacts 
photosensitivity following UVB exposure in individuals with cutaneous 
lupus erythematosus (CLE). 
Secondary Objectives 
1. To evaluate changes in cutaneous disease activity in individuals with 
CLE after a 25-day regimen of tofacitinib. 
2. To evaluate changes in systemic lupus erythematosus (SLE) disease 
activity in individuals with CLE after a 25-day regimen of tofacitinib. 
3. To evaluate safety and toxicity of a 25-day regimen of tofacitinib for 
individuals with CLE. 
Study Design
This is a single-arm, multi-site, proof-of-concept study of 10 participants 
with CLE. Consenting individuals meeting all entry criteria will undergo 25 
days of treatment with tofacitinib (11 mg orally (PO) daily) with evaluation 
of UVB-mediated cutaneous apoptosis and ancillary mechanistic studies 
before and after treatment.  Post-screening study visits will be conducted 
on Days 0 (Visit 1), 1 (Visit 2), 14 (Visit 3), 25 (Visit 4), 26 (Visit 5), and 40 
(Visit 6) to (1) evaluate adverse events, vital signs, hematology and 
chemistry, study drug compliance, medication use, and disease status, (2) 
conduct UVB phototesting, and (3) collect skin biopsies and blood samples 
for mechanistic studies. Tofacitinib will be distributed to eligible 
participants at Visit 2 (Day 1) and the first dose will be taken on Day 2. The 
last dose is the morning of Visit 5 (Day 26). Participants are allowed to 
continue on their stable background therapies for lupus according to 
Section 7.1.2, Other Permitted Concomitant Medications. 
Please refer to Section 8.1.1, Exceptions to Visit Windows, and Section 6.6, 
Resumption of Investigational Product, for more information regarding 
delays to visits 4 and 5. 


Autoimmunity Centers of Excellence 
Confidential 
Page 4 of 52 
ALE11 
Version 7.0 
October 25, 2023 
Primary Endpoint
Primary Endpoint
The change in percentage of UVB-induced apoptotic epidermal cells from 
Visit 2 (Day 1) (pre-treatment) to Visit 5 (Day 26) (post-treatment). 
Percentage of UVB-induced apoptotic cells at a visit is defined as the 
difference between the percentage of apoptotic epidermal cells in the 
UVB-exposed biopsy and percentage of apoptotic epidermal cells in the 
unexposed biopsy at the same visit. More information can be found in 
Section 8.5.5, Research Assessments.   
 
Accrual Objective
10 participants completing two phototests at least 3 weeks apart.
Study Duration
This study is estimated to last 1 year.
Treatment Description
Participants will receive a 25-day regimen of tofacitinib 11 mg daily.
Inclusion Criteria
1. Cutaneous lupus erythematosus based upon all of the following:
a. a clinical diagnosis made by a rheumatologist or dermatologist 
of one of the following:  acute cutaneous lupus 
erythematosus, subacute cutaneous lupus, or chronic 
cutaneous lupus erythematosus;   
b. active skin disease within 5 years prior to screening. 
Participants may have concomitant SLE. 
2. SLEDAI-2K score ≤4 (clinical criteria only, excludes all laboratory 
criteria) for all participants regardless of whether they have 
concomitant SLE. 
3. If taking oral corticosteroids, the dose must be ≤ 10 mg daily of 
prednisone (or equivalent), stable dose for at least 4 weeks, and not 
anticipated to change over the course of the study. 
4. If taking oral anti-malarial medications, the dose(s) must be ≤ 100 mg 
daily for quinacrine or/and ≤ 400 mg daily for hydroxychloroquine, 
stable for at least 6 months, and not anticipated to change over the 
course of the study. 
5. If taking oral or subcutaneous methotrexate, the dose must be ≤ 25 
mg weekly, stable for at least 4 weeks, and not anticipated to change 
over the course of the study. 
6. If taking oral leflunomide, the dose must be ≤ 20 mg daily, stable for at 
least 4 weeks, and not anticipated to change over the course of the 
study. 
7. If taking oral mycophenolate mofetil (MMF) or mycophenolic acid, the 
dose must be equivalent to ≤ 3000 mg of MMF daily, stable for at least 
4 weeks, and not anticipated to change over the course of the study.  
  
8. Adults 18 to 65 years of age at screening. 


Autoimmunity Centers of Excellence 
Confidential 
Page 5 of 52 
ALE11 
Version 7.0 
October 25, 2023 
9. All participants and/or their sexual partners who engage in sexual 
activity that could lead to pregnancy must be willing to use complete 
abstinence or an FDA-regulated form of contraception for the 
duration of the study and for at least one month after discontinuation 
of study drug to prevent pregnancy. Highly effective birth control 
methods include, but are not limited to, hormonal contraception, an 
intrauterine device, or surgical options. Periodic abstinence and 
withdrawal are not acceptable methods of birth control. 
Exclusion Criteria
1. Inability or unwillingness of a participant to give written informed 
consent or comply with study protocol. 
2. Current or recent history, within the last year, of uncontrolled 
clinically significant renal, hepatic, hematologic, gastrointestinal, 
metabolic, endocrine, pulmonary, cardiac, or neurologic disease or 
significant impairment that might negatively impact the participant’s 
ability to participate or that may put a participant at increased risk. 
3. Potential active nephritis and/or urinary tract infection at screening, 
defined as any one of the following determined at screening unless 
otherwise specified: 
a. >10 RBCs /hpf, 
b. >5 WBCs /hpf with either positive nitrites or greater than a 
trace leukocyte esterase, 
c. Signs or symptoms of a urinary tract infection,  
d. For individuals with no history of nephritis: Urine protein 
(mg/dL): creatinine (mg/dL) ratio (Pr/Cr)>0.5 at screening or a 
Pr/Cr level that has exceeded 1.0 in the prior 12 months,  
e. For individuals with a history of nephritis: A rise in Pr/Cr of 
>0.5 over the prior 3-6 months prior to screening. 
4. History of severe gastrointestinal narrowing or strictures. 
5. Medically confirmed history of diverticulitis or chronic, ulcerative 
lower gastrointestinal (GI) disease such as Crohn’s disease, ulcerative 
colitis, or other symptomatic, lower GI conditions that might 
predispose a participant to perforations. 
6. History of thrombosis, pulmonary embolism, or antiphospholipid 
syndrome. 
7. History of any one of the following anti-phospholipid antibodies: 
a. Positive lupus anticoagulant test, or  
b. Anti-β2-glycoprotein I IgG ELISA titer ≥ 40 GPL, or  
c. Anti-cardiolipin IgG ELISA titer ≥ 40 GPL.   
8. History of chronic pulmonary disease requiring supplemental oxygen 
including chronic obstructive pulmonary disease (COPD) requiring 
chronic treatment, interstitial lung disease (ILD) requiring 


Autoimmunity Centers of Excellence 
Confidential 
Page 6 of 52 
ALE11 
Version 7.0 
October 25, 2023 
immunosuppressive therapy, and asthma requiring chronic steroid 
(other than inhaled steroid) or biologic therapy. 
9. History of moderate to severe atherosclerotic cardiovascular disease 
as evidenced by prior coronary artery bypass surgery, coronary artery 
stent placement, myocardial infarction, symptomatic carotid arterial 
disease, peripheral vascular disease, abdominal aortic aneurysm; or 
angina within the past 8 weeks prior to Visit 1 (Day 0).  
10. History of keloid scarring. 
11. History of any lymphoproliferative disorder or other malignancy with 
the exception of successfully treated or excised basal cell or squamous 
cell skin cancer or cervical cancer in situ. 
12. Other autoimmune diseases likely to require immunosuppression. 
13. Any of the following lab results at screening: 
a. Hemoglobin <9.5 g/dL 
b. White Blood Cell count <3.5 x 109/L 
c. Absolute Neutrophil count <1.2 x 109/L 
d. Platelet count <120 x 109/L 
e. Absolute Lymphocyte count <0.75 x 109/L 
f. 
Alanine Aminotransferase (ALT) or Aspartate 
Aminotransferase (AST) > 1.5 × the upper limit of normal 
(ULN) 
g. Total bilirubin > ULN 
h. Estimated glomerular filtration rate [GFR] <60mL/min/1.73 m2 
i. 
Triglycerides ≥ 300 mg/dL (fasting not required) 
j. 
Total Cholesterol ≥ 240 mg/dL (fasting not required). 
14. Major surgery < 8 weeks prior to Visit 1 (Day 0). 
15. Hospitalized for serious infection < 4 weeks prior to Visit 1 (Day 0). 
16. Chronic infections other than chronic or intermittent uncomplicated 
urinary tract infections (including but not limited to tuberculosis, 
chronic pyelonephritis, osteomyelitis). 
17. Presumed or documented COVID-19 infection within 30 days prior to 
Visit 1 (Day 0). 
18. Recent (within one month prior to screening) close contact with a 
person who has active TB infection.  
19. History of untreated active or latent TB infection.  
20. History of incompletely treated active or latent TB infection unless at 
least one month of treatment has been completed prior to screening. 
21. Positive Interferon-Gamma Release Assay (IGRA) or positive purified 
protein derivative tuberculin skin test (PPD) (> 5mm induration) at 
screening.  
22. An indeterminate IGRA at screening unless followed by a subsequent 
negative IGRA or negative PPD. 
23. History of human immunodeficiency virus (HIV). 


Autoimmunity Centers of Excellence 
Confidential 
Page 7 of 52 
ALE11 
Version 7.0 
October 25, 2023 
24. A positive test for HIV antigen/antibody or nucleic acid test (NAT) at 
screening.   
25. History of a hepatitis B infection. 
26. A positive test for hepatitis B surface antigen or hepatitis B core 
antibody at screening. 
27. History of a hepatitis C infection. 
28. A positive test for hepatitis C antibody (regardless of whether 
hepatitis C RNA levels are undetectable) at screening. 
29. History of recurrent (more than one episode) herpes zoster, one or 
more episodes of any of the following: herpes zoster ophthalmicus, or 
disseminated herpes zoster, or disseminated herpes simplex. 
30. Current, recent (< 4 weeks prior to Visit 1 (Day 0)) or chronic use of 
antibiotic medication, except for suppression of chronic/recurrent 
urinary tract infection, which is allowed. 
31. Simultaneous use of more than one of the following: leflunomide, 
methotrexate and MMF. 
32. Any of the following active medications (oral or parenteral): 
cyclosporine, voclosporin, cyclophosphamide, tacrolimus, rituximab or 
other anti-CD20s, or any other investigational or marketed biologic 
with immunomodulatory properties within a year prior to Visit 1 (Day 
0). 
33. Any of the following medications (oral or parenteral): azathioprine or 
belimumab within 3 months prior to Visit 1 (Day 0). 
34. Any prior treatment with cell-depleting therapies other than anti-
CD20s including but not limited to CAMPATH, anti-CD4, anti-CD5, anti-
CD3, anti-CD19 products. 
35. Intravenous or intramuscular corticosteroids within 2 weeks prior to 
Visit 1 (Day 0). 
36. Treatment with any investigational agent ≤ 4 weeks or ≤ 5 half-lives of 
the investigational drug prior to Visit 1 (Day 0), whichever is longer. 
37. Treatment with more than one dose of ketoconazole within one week 
of screening.  
38. Any prior treatment with chlorambucil, bone marrow transplantation, 
or total lymphoid irradiation. 
39. Vaccinated or exposed by close contact, e.g., within a household, to a 
live/attenuated vaccine ≤ 6 weeks prior to Visit 1 (Day 0); or is 
expected to be vaccinated or to have household exposure to these 
vaccines during treatment or during the 6 weeks following 
discontinuation of study medication. 
40. Received a non-live vaccine ≤ 2 weeks prior to initiation of study drug, 
or unwillingness of a participant to delay non-live vaccination until 1 
month after completion of study therapy. 
41. Pregnant or breastfeeding females. 


Autoimmunity Centers of Excellence 
Confidential 
Page 8 of 52 
ALE11 
Version 7.0 
October 25, 2023 
42. History of alcohol or substance abuse, unless in full remission for 
greater than 6 months prior to first dose of study drug. 
43. Past or current medical or psychiatric conditions or findings from 
physical examination or laboratory testing that are not listed above, 
which, in the opinion of the investigator, may pose additional risks 
from participation in the study, may interfere with the participant’s 
ability to comply with study requirements or that may impact the 
quality or interpretation of the data obtained from the study. 
Study Stopping Rules
There are no pre-specified study stopping rules.
 
An ad hoc comprehensive DSMB review will occur as a result of any of the 
following events:  
 
Any death considered possibly or definitely related to study 
treatment or procedures. 
 
The occurrence in 2 participants of Grade 3 or higher AEs or 
SAEs with the same MedDRA preferred terms considered at 
least possibly related to study treatment or procedures.  
 
The occurrence in 2 participants of Grade 3 or higher 
infections. 
 
Any grade 2 or higher thromboembolic event. 
After review of the data, the DSMB will make recommendations regarding 
the study conduct and/or continuation.  
 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 9 of 52 
ALE11 
Version 7.0 
October 25, 2023 
Table of Contents 
Glossary of Abbreviations ..................................................................................................................................................... 13 
1. 
Background and Rationale ............................................................................................................................................ 15 
1.1. 
Background and Scientific Rationale ..................................................................................................................... 15 
1.2. 
Rationale for Selection of Investigational Product ............................................................................................... 15 
1.3. 
Preclinical Experience ........................................................................................................................................... 16 
1.4. 
Clinical Studies ...................................................................................................................................................... 16 
2. 
Study Hypotheses/Objectives ....................................................................................................................................... 17 
2.1. 
Hypotheses............................................................................................................................................................ 17 
2.2. 
Primary Objective .................................................................................................................................................. 17 
2.3. 
Secondary Objectives ............................................................................................................................................ 17 
3. 
Study Design .................................................................................................................................................................. 17 
3.1. 
Description of Study Design .................................................................................................................................. 17 
3.1.1. 
Considerations Regarding COVID-19 ............................................................................................................. 18 
3.2. 
Primary Endpoint .................................................................................................................................................. 18 
3.3. 
Secondary Endpoints ............................................................................................................................................ 18 
3.4. 
Stratification, Randomization, and Blinding/Masking .......................................................................................... 19 
4. 
Selection of Participants ............................................................................................................................................... 19 
4.1. 
Study Population ................................................................................................................................................... 19 
4.2. 
Inclusion Criteria ................................................................................................................................................... 19 
4.3. 
Exclusion Criteria ................................................................................................................................................... 20 
5. 
Known and Potential Risks and Benefits to Participants .............................................................................................. 22 
5.1. 
Risks of Tofacitinib as cited in US Package Insert ................................................................................................. 22 
5.2. 
Risks of Tofacitinib cited in Medical Literature and FDA Drug Safety Communications ...................................... 24 
5.3. 
Risks of Other Protocol Specified Medications ..................................................................................................... 24 
5.4. 
Risks of Study Procedures ..................................................................................................................................... 24 
5.5. 
Summary of Potential Benefits ............................................................................................................................. 25 
6. 
Investigational Agent /Device/Intervention ................................................................................................................. 25 
6.1. 
Investigational Agents ........................................................................................................................................... 25 
6.1.1. 
XELJANZ® XR (tofacitinib) .............................................................................................................................. 25 
6.2. 
Drug Accountability ............................................................................................................................................... 26 
6.3. 
Assessment of Participant Compliance with Investigational Agent ..................................................................... 26 
6.4. 
Toxicity Prevention and Management .................................................................................................................. 26 


Autoimmunity Centers of Excellence 
Confidential 
Page 10 of 52 
ALE11 
Version 7.0 
October 25, 2023 
6.5. 
Discontinuation/Suspension of Investigational Agent .......................................................................................... 27 
6.5.1. 
Permanent Discontinuation of Investigational Agent ................................................................................... 27 
6.5.2. 
Temporary Suspension of Investigational Agent .......................................................................................... 27 
6.6. 
Resumption of Investigational Product ................................................................................................................ 28 
7. 
Other Medications ........................................................................................................................................................ 28 
7.1. 
Concomitant Medications ..................................................................................................................................... 28 
7.1.1. 
Protocol-mandated ....................................................................................................................................... 28 
7.1.2. 
Other Permitted Concomitant Medications ................................................................................................. 28 
7.2. 
Prophylactic Medications ...................................................................................................................................... 29 
7.3. 
Prohibited Medications ......................................................................................................................................... 29 
7.4. 
Rescue Medications .............................................................................................................................................. 29 
8. 
Study Procedures .......................................................................................................................................................... 29 
8.1. 
Visit Windows ....................................................................................................................................................... 29 
8.1.1. 
Exception to Visit Window Rules .................................................................................................................. 30 
8.2. 
Screening and Enrollment ..................................................................................................................................... 30 
8.3. 
Unscheduled Visits ................................................................................................................................................ 30 
8.4. 
Early Termination Visits ........................................................................................................................................ 30 
8.5. 
Study Procedures and Assessments ...................................................................................................................... 31 
8.5.1. 
Study Drug ..................................................................................................................................................... 31 
8.5.2. 
General Assessments .................................................................................................................................... 31 
8.5.3. 
Clinical Assessments...................................................................................................................................... 31 
8.5.4. 
Clinical Laboratory Assessments ................................................................................................................... 32 
8.5.5. 
Research Assessments .................................................................................................................................. 32 
9. 
Mechanistic Assays ....................................................................................................................................................... 36 
10. 
Biospecimen Storage................................................................................................................................................. 36 
11. 
Criteria for Participant and Study Completion and Premature Study Termination.................................................. 36 
11.1. Participant Completion ......................................................................................................................................... 36 
11.2. Participant Withdrawal Criteria ............................................................................................................................ 36 
11.3. Participant Replacement ....................................................................................................................................... 37 
11.4. Follow-up after Early Study Withdrawal ............................................................................................................... 37 
11.5. Study Stopping Rules............................................................................................................................................. 37 
12. 
Safety Monitoring and Reporting ............................................................................................................................. 37 
12.1. Overview ............................................................................................................................................................... 37 


Autoimmunity Centers of Excellence 
Confidential 
Page 11 of 52 
ALE11 
Version 7.0 
October 25, 2023 
12.2. Definitions ............................................................................................................................................................. 37 
12.2.1. 
Adverse Event (AE) ........................................................................................................................................ 37 
12.2.2. 
Suspected Adverse Reaction ......................................................................................................................... 38 
12.2.3. 
Unexpected Adverse Event ........................................................................................................................... 38 
12.2.4. 
Serious Adverse Event ................................................................................................................................... 38 
12.3. Grading and Attribution of Adverse Events .......................................................................................................... 38 
12.3.1. 
Grading Criteria ............................................................................................................................................. 38 
12.3.2. 
Attribution Definitions .................................................................................................................................. 40 
12.4. Collection and Recording of Adverse Events ........................................................................................................ 40 
12.4.1. 
Collection Period ........................................................................................................................................... 40 
12.4.2. 
Collecting Adverse Events ............................................................................................................................. 40 
12.4.3. 
Recording Adverse Events ............................................................................................................................. 41 
12.5. Reporting of Serious Adverse Events and Adverse Events ................................................................................... 41 
12.5.1. 
Reporting of Adverse Events ......................................................................................................................... 41 
12.5.2. 
Reporting of Serious Adverse Events to DAIT/NIAID (Sponsor) .................................................................... 41 
12.5.3. 
Reporting to FDA ........................................................................................................................................... 42 
12.5.4. 
Reporting of Adverse Events to IRBs/IECs .................................................................................................... 42 
12.6. Pregnancy Reporting ............................................................................................................................................. 42 
12.7. Reporting of Other Safety Information ................................................................................................................. 42 
12.8. Review of Safety Information ............................................................................................................................... 43 
12.8.1. 
Medical Monitor Review ............................................................................................................................... 43 
12.8.2. 
Data Safety and Monitoring Board Review ................................................................................................... 43 
13. 
Statistical Considerations and Analytical Plan .......................................................................................................... 44 
13.1. Overview ............................................................................................................................................................... 44 
13.2. Endpoints .............................................................................................................................................................. 44 
13.3. Measures to Minimize Bias ................................................................................................................................... 44 
13.4. Analysis Plan .......................................................................................................................................................... 44 
13.4.1. 
Analysis Populations ..................................................................................................................................... 44 
13.4.2. 
Primary Analysis of Primary Endpoint ........................................................................................................... 44 
13.4.3. 
Supportive Analyses of the Primary Endpoint .............................................................................................. 45 
13.4.4. 
Analyses of Secondary Endpoints ................................................................................................................. 45 
13.4.5. 
Descriptive Analyses ..................................................................................................................................... 46 
13.5. Interim Analyses .................................................................................................................................................... 46 


Autoimmunity Centers of Excellence 
Confidential 
Page 12 of 52 
ALE11 
Version 7.0 
October 25, 2023 
13.6. Statistical Hypothesis ............................................................................................................................................ 46 
13.7. Sample Size Considerations .................................................................................................................................. 46 
14. 
Identification and Access to Source Data ................................................................................................................. 47 
14.1. Source Data ........................................................................................................................................................... 47 
14.2. Access to Source Data ........................................................................................................................................... 48 
15. 
Quality Assurance and Quality Control ..................................................................................................................... 48 
16. 
Protocol Deviations ................................................................................................................................................... 49 
16.1. Protocol Deviation Definitions .............................................................................................................................. 49 
16.2. Reporting and Managing Protocol Deviations ...................................................................................................... 49 
17. 
Ethical Considerations and Compliance with Good Clinical Practice ........................................................................ 49 
17.1. Statement of Compliance ..................................................................................................................................... 49 
17.2. Informed Consent Process .................................................................................................................................... 50 
17.3. Privacy and Confidentiality ................................................................................................................................... 50 
18. 
Publication Policy ...................................................................................................................................................... 50 
19. 
References ................................................................................................................................................................ 51 
 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 13 of 52 
ALE11 
Version 7.0 
October 25, 2023 
Glossary of Abbreviations 
ALT
Alanine Aminotransferase
ANC
Absolute Neutrophil Count
APGAR
Appearance, Pulse, Grimace, Activity, and Respiration
AST
Aspartate Aminotransferase
CAPA
Corrective Action/Preventive Action
CBC
Complete Blood Count
CFR
Code of Federal Regulations
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CLE
Cutaneous Lupus Erythematosus
CRF
Case Report Form
CTCAE
Common Terminology Criteria for Adverse Events
DAIT
Division of Allergy, Immunology, and Transplantation
DLE
Discoid Lupus Erythematosus
DMARDs
Disease-Modifying Anti-Rheumatic Drugs
DSMB
Data Safety Monitoring Board
eCRF
Electronic Case Report Form
ESR
Erythrocyte Sedimentation Rate
FDA
Food and Drug Administration
FFPE
Formalin Fixed Paraffin-Embedded
GCP
Good Clinical Practice
GI
Gastrointestinal
HDL
High-Density Lipoprotein
Hpf
High powered field
ICH
International Council for Harmonization
IGRA
Interferon-Gamma Release Assay
IND
Investigational New Drug
IFNk 
Interferon kappa 
IRB
Institutional Review Board
JAK-1
Janus Kinase 1 Inhibitor 
LDL
Low-Density Lipoprotein 
MED
Minimal Erythema Dose
MMF
Mycophenolate mofetil


Autoimmunity Centers of Excellence 
Confidential 
Page 14 of 52 
ALE11 
Version 7.0 
October 25, 2023 
NAT
Nucleic Acid Test
NCI
National Cancer Institute
NIAID
National Institute of Allergy and Infectious Diseases
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
PBMCs
Peripheral Blood Mononuclear Cells
pcJIA
Polyarticular Course Juvenile Idiopathic Arthritis
PHI
Personal Health Identifiers 
PI
[Site] Principal Investigator
PP1
Per Protocol 1
PP2
Per Protocol 2 
PPD
Purified Protein Derivative
Pr/Cr
Urinary Protein (mg/dL):Creatinine (mg/dL) ratio
RA
Rheumatoid Arthritis
SACCC
Statistical and Clinical Coordinating Center
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SAR
Suspected Adverse Reaction
SD
Standard Deviation 
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SUSAR
Serious Unexpected Suspected Adverse Reaction
SLE
Systemic Lupus Erythematosus
SS
Safety Sample
TB
Tuberculosis 
TNF
Tumor Necrosis Factor
ULN
Upper Limit of Normal
UV
Ultraviolet 
UVB
Ultraviolet B
 
 
 
 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 15 of 52 
ALE11 
Version 7.0 
October 25, 2023 
 
1. Background and Rationale  
1.1. Background and Scientific Rationale 
Disease Impact:  Exposure to ultraviolet (UV) light can serve as a trigger for cutaneous lupus erythematosus (CLE) and 
systemic lupus erythematosus (SLE) disease flares[1] making it one of the few definitive known triggers for these 
diseases. Complicating our ability to treat UV light-induced cutaneous and systemic lupus disease flares is an incomplete 
understanding of the mechanisms which drive this phenomenon. Targeted systemic treatment to reduce the effect of 
UV light would be a novel and important mechanism for reduction in disease flare rate and potentially even treatment 
of these patients.     
Scientific Rationale of Proposed Study: UV light is a known trigger of CLE lesions[2] and induces apoptosis through 
several pathways[3]. It has been reported that CLE lesions are characterized by increased apoptosis[4]. One hypothesis 
on the etiology of CLE lesions is that increased apoptosis following ultraviolet B (UVB) exposure of “normal skin” leads to 
autoantigen exposure in an environment where antigen clearance is impaired (as in lupus)[5]. This coupled with a robust 
keratinocyte-mediated inflammatory response promotes inflammatory cell recruitment to the skin where autoantigens 
are taken up, processed, and presented to autoreactive T cells.   Interferon kappa (IFNκ) is overexpressed in non-lesional 
lupus skin and is a key regulator of apoptotic responses to UVB. Indeed, enhanced UVB-driven apoptosis can be induced 
by overexpressing IFNκ in N/TERT keratinocytes.  Further, deletion of IFNκ is sufficient to significantly impair UVB-
mediated apoptosis[6]. This suggests that the level of IFNκ present can serve as a rheostat for UVB-mediated apoptosis. 
Indeed, in non-lesional keratinocytes, enhanced apoptosis in SLE versus control can be abrogated by blocking type I IFN 
signaling via a Janus Kinase 1 (JAK1) inhibitor[6]. Patients with isolated CLE lesions and those with CLE as a manifestation 
of SLE exhibit high levels of IFNκ in their skin lesions, and both groups of patients have indistinguishable cutaneous IFN 
signatures [6, 7]. Thus, in CLE-prone skin, photosensitive reactions driven by keratinocyte apoptosis and increased 
cytokine production are primed for by IFNκ and are potentially inhibited through blockade of IFN signaling via JAK 
inhibition.   
There is a gap in our knowledge regarding how non-lesional skin of individuals with CLE responds to UV light and 
whether blockade of IFN signaling will alleviate photosensitivity.  Small trials and case reports have suggested that 
tofacitinib is beneficial in SLE and CLE patients, but none of these studies have evaluated photosensitivity as part of their 
studies[8] [9, 10]. This study will provide information on how JAK blockade impacts photosensitive responses and 
whether this strategy could be considered as a prophylactic measure to prevent cutaneous and systemic lupus flares. As 
CLE is a known manifestation of photosensitive reactions, we will study CLE patients for this trial. 
 
1.2. Rationale for Selection of Investigational Product 
What is the nature of the product to be tested? Tofacitinib is a Food and Drug Administration (FDA)-approved 
JAK3/JAK1 inhibitor that is used for treatment of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and 
polyarticular course Juvenile Idiopathic Arthritis (pcJIA). Despite its ability to block both JAK3 and JAK1 signaling, it is able 
to inhibit type I IFN signaling and IL-6 pathways with equal efficacy to baricitinib, where JAK1 is its primary target [11]. 
Based on published data, which shows blockade of JAK1 signaling in vitro normalizes SLE keratinocyte cell death after 
UVB [6], we hypothesize that treating individuals with CLE with tofacitinib will reduce UVB-mediated apoptosis and 


Autoimmunity Centers of Excellence 
Confidential 
Page 16 of 52 
ALE11 
Version 7.0 
October 25, 2023 
consequently improve photosensitivity parameters. We thus propose to test this hypothesis by treating patients with 
tofacitinib 11 mg daily for 25 days and by performing photosensitivity testing and skin biopsies before and after 
treatment to investigate the impact on disease mechanisms.  
Xeljanz®(tofacitinib) 5 mg BID and Xeljanz® XR (tofacitinib) 11 mg daily are approved for rheumatic conditions.  Both 
have shown equivalent efficacy[12]. For this protocol, Xeljanz® XR 11 mg once daily was selected as the dosing regimen 
in order to reduce the number of pills the participants are required to take on a daily basis and thus increase compliance 
with dosing. Twenty-five days of dosing was chosen to provide for normalization of steady state levels with once daily 
dosing while limiting the overall exposure to the medication. Steady state of Xeljanz® XR 11 mg occurs within 5 days of 
dosing[13] to levels sufficient to inhibit peripheral immune signaling[14]. However, tissue penetration and signaling 
effects in the skin may require longer exposure, thus the 25-day dosing regimen prior to phototesting will be employed 
in this study. 
Advantages of Using Tofacitinib 
1. Once daily dosing 
2. Has been tested in small Phase I/II study of SLE patients without safety signals[8]. 
3. FDA approved for other autoimmune conditions, i.e., rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, 
and pcJIA, with extensive safety profile in these conditions. 
1.3. Preclinical Experience 
Murine studies support potential efficacy in lupus. In lupus-prone MRL/lpr mice, treatment with tofacitinib results in 
improvement of cutaneous lesions as well as a decreased risk of developing nephritis[15]. Additional follow-up murine 
studies in the MRL/lpr model have shown that tofacitinib impairs the survival and effector functions of pathogenic CD8+ T 
resident memory cells[16]. In an interferon-driven model of murine lupus, NZB/NZW F1, tofacitinib also reduced 
interferon signatures and improvement in nephritis[17]. 
1.4. Clinical Studies 
Tofacitinib is FDA approved for the treatment of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and pcJIA, and 
dosed at 5 mg twice daily (BID) or 11 mg daily (extended release, XR). Tofacitinib is not currently approved for use in CLE 
or SLE patients. A Phase I/II study which enrolled 30 SLE patients with mild to moderate disease activity to assess safety 
in SLE patients (no skin measurements taken) with 56 days of active drug treatment of 5 mg BID, did not identify any 
serious adverse events (SAE) and there was no increase in adverse events over placebo[8]. A case series also reported 
partial to complete efficacy for skin and arthritis in 10 patients with SLE treated with tofacitinib 5 mg BID[18]. Currently, 
there are several additional small studies of tofacitinib: one with plans to enroll 12 adult discoid lupus erythematosus 
(DLE) patients  in an open label pilot study to look at clinical changes[19]; one enrolling 20 young (18-30 years) patients 
with CLE for pharmacodynamics studies. Data from dose-ranging studies in SLE are not available. No long-term studies to 
evaluate toxicology or efficacy in lupus patients have yet been performed.  
 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 17 of 52 
ALE11 
Version 7.0 
October 25, 2023 
2. Study Hypotheses/Objectives 
2.1. Hypotheses 
In individuals with CLE, a 25-day regimen of tofacitinib will: 
 
reduce UVB-mediated cutaneous apoptosis,  
 
reduce UVB-mediated inflammatory gene transcription, and  
 
increase minimal erythema dose (MED) after UVB exposure. 
2.2. Primary Objective 
The primary objective is to determine whether a 25-day regimen of tofacitinib impacts photosensitivity following 
UVB exposure in individuals with CLE. 
 
Photosensitivity parameters will be measured before and after tofacitinib treatment and will include: UVB-mediated 
cutaneous apoptosis, UVB-mediated inflammatory gene transcription, and MED in response to UVB exposure. 
2.3. Secondary Objectives 
The secondary objectives are as follows: 
 
To evaluate changes in cutaneous disease activity in individuals with CLE after a 25-day regimen of tofacitinib. 
 
To evaluate changes in SLE activity in individuals with CLE after a 25-day regimen of tofacitinib. 
 
To evaluate safety and toxicity of a 25-day regimen of tofacitinib for individuals with CLE. 
3. Study Design 
3.1. Description of Study Design 
This is a single-arm, multi-site, proof-of-concept study of 10 participants with CLE.  Consenting individuals meeting all 
entry criteria will undergo 25 days of treatment with tofacitinib (11 mg orally (PO) daily) with evaluation of UVB-
mediated cutaneous apoptosis and ancillary mechanistic studies before and after treatment.  Post-screening study visits 
will be conducted on Days 0 (Visit 1), 1 (Visit 2), 14 (Visit 3), 25 (Visit 4), 26 (Visit 5), and 40 (Visit 6) to (1) evaluate 
adverse events, vital signs, hematology and chemistry, study drug compliance, medication use, and disease status, (2) 
conduct UVB phototesting, and (3) collect skin biopsies and blood samples for mechanistic studies (See Figure 1).  
Tofacitinib will be distributed to eligible participants at Visit 2 (Day 1) and the first dose will be taken on Day 2. The last 
dose is the morning of Visit 5 (Day 26). Participants are allowed to continue on their stable background therapies for 
lupus according to Section 7.1.2, Other Permitted Concomitant Medications.  
Please refer to Section 8.1.1, Exceptions to Visit Windows, and Section 6.6, Resumption of Investigational Product, for 
more information regarding delays to visits 4 and 5. 


Autoimmunity Centers of Excellence 
Confidential 
Page 18 of 52 
ALE11 
Version 7.0 
October 25, 2023 
 
 
 
Figure 1. Study Schematic 
3.1.1. Considerations Regarding COVID-19 
May 11, 2023, marked the end of the COVID-19 public health emergency (PHE) declaration in the US. The CDC states 
that many people in the United States now have some protection or immunity against COVID-19 due to vaccination, 
previous infection, or both. This immunity, combined with the availability of tests and treatments, has greatly reduced 
the risk of severe illness, hospitalization, and death from COVID-19 for many people 
(https://www.cdc.gov/coronavirus/2019-ncov/your-health/covid-by-county.html).  
At the same time, some people—such as those who are older, are immunocompromised, have certain disabilities, or 
have certain underlying health conditions—continue to be at higher risk for serious illness. Mitigating risks of 
infections, including from endemic COVID-19, in immunocompromised populations remains important.  
Participants are strongly recommended to be up to date with COVID-19 vaccinations per current CDC 
recommendations at the time of screening with last vaccine at least 14 days prior to Visit 1 (Day 0). 
3.2. Primary Endpoint 
The primary endpoint is the change in percentage of UVB-induced apoptotic epidermal cells from Visit 2 (Day 1) (pre-
treatment) to Visit 5 (Day 26) (post-treatment). Percentage of UVB-induced apoptotic cells at a visit is defined as the 
difference between the percentage of apoptotic epidermal cells in the UVB-exposed biopsy and percentage of apoptotic 
epidermal cells in the unexposed biopsy at the same visit. More information can be found in Section 8.5.5, Research 
Assessments. 
 
3.3. Secondary Endpoints 
1. Change in MED due to UVB from Visit 2 (Day 1) to Visit 5 (Day 26)  


Autoimmunity Centers of Excellence 
Confidential 
Page 19 of 52 
ALE11 
Version 7.0 
October 25, 2023 
2. Change in UVB-induced expression of inflammatory genes in skin from Visit 2 (Day 1) to Visit 5 (Day 26), based 
on enumeration of RNA transcripts.  UVB-induced expression is defined as the difference in expression 
measured in the biopsy exposed at the Visit 2 (Day 1) 1x MED and that measured in the unexposed biopsy 
3. Change in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity score from Visit 1 
(Day 0) to Visit 4 (Day 25) 
4. Change in CLASI damage score from Visit 1 (Day 0) to Visit 4 (Day 25) 
5. Change in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score from Visit 1 (Day 0) 
to Visit 4 (Day 25) 
6. Changes in laboratory parameters 
7. Incidence of adverse events 
3.4. Stratification, Randomization, and Blinding/Masking  
This is a single-arm open-label study. There are no plans for stratification, randomization, or masking. 
4. Selection of Participants  
4.1. Study Population 
This study can fulfill its objectives only if appropriate participants are enrolled.  The following eligibility criteria are 
designed to select participants for whom the study is considered appropriate.  All relevant medical and nonmedical 
conditions should be taken into consideration when deciding whether a particular participant is suitable for this 
protocol. For this Phase 1 study, conditions indicative of serious disease, such as CNS lupus or lupus nephritis, are 
excluded by limiting the total SLEDAI-2K score for clinical manifestations to ≤4 at entry.   
4.2. Inclusion Criteria 
Individuals must meet all of the following inclusion criteria to be eligible for enrollment in the study: 
1. Cutaneous lupus erythematosus based upon all of the following: 
a. a clinical diagnosis made by a rheumatologist or dermatologist of one of the following:  acute cutaneous 
lupus erythematosus, subacute cutaneous lupus, or chronic cutaneous lupus erythematosus;  
b. active skin disease within 5 years prior to screening.  
Participants may have concomitant SLE. 
2. SLEDAI-2K score ≤4 (clinical criteria only, excludes all laboratory criteria) for all participants regardless of 
whether they have concomitant SLE. 
3. If taking oral corticosteroids, the dose must be ≤ 10 mg daily of prednisone (or equivalent), stable dose for at 
least 4 weeks, and not anticipated to change over the course of the study. 
4. If taking oral anti-malarial medications, the dose(s) must be ≤ 100 mg daily for quinacrine or/and ≤ 400 mg daily 
for hydroxychloroquine, stable for at least 6 months, and not anticipated to change over the course of the study. 
5. If taking oral or subcutaneous methotrexate, the dose must be ≤ 25 mg weekly, stable for at least 4 weeks, and 
not anticipated to change over the course of the study. 
6. If taking oral leflunomide, the dose must be ≤ 20 mg daily, stable for at least 4 weeks, and not anticipated to 
change over the course of the study. 
7. If taking oral mycophenolate mofetil (MMF) or mycophenolic acid, the dose must be equivalent to ≤ 3000 mg of 
MMF daily, stable for at least 4 weeks, and not anticipated to change over the course of the study. 
8. Adults 18 to 65 years of age at screening. 


Autoimmunity Centers of Excellence 
Confidential 
Page 20 of 52 
ALE11 
Version 7.0 
October 25, 2023 
9. All participants and/or their sexual partners who engage in sexual activity that could lead to pregnancy must be 
willing to use complete abstinence or an FDA-regulated form of contraception for the duration of the study and 
for at least one month after discontinuation of study drug to prevent pregnancy. Highly effective birth control 
methods include, but are not limited to, hormonal contraception, an intrauterine device, or surgical options. 
Periodic abstinence and withdrawal are not acceptable methods of birth control. 
4.3. Exclusion Criteria 
Individuals who meet any of these criteria are not eligible for enrollment as study participants:  
1. Inability or unwillingness of a participant to give written informed consent or comply with study protocol. 
2. Current or recent history, within the last year, of uncontrolled clinically significant renal, hepatic, hematologic, 
gastrointestinal, metabolic, endocrine, pulmonary, cardiac, or neurologic disease or significant impairment that 
might negatively impact the participant’s ability to participate or that may put a participant at increased risk. 
3. Potential active nephritis and/or urinary tract infection at screening, defined as any one of the following 
determined at screening unless otherwise specified: 
a. >10 RBCs /hpf, 
b. >5 WBCs /hpf with either positive nitrites or greater than a trace leukocyte esterase,  
c.  Signs or symptoms of a urinary tract infection, 
d. For individuals with no history of nephritis: Urine protein (mg/dL): creatinine (mg/dL) ratio (Pr/Cr)>0.5 at 
screening or a Pr/Cr level that has exceeded 1.0 in the prior 12 months, 
e. For individuals with a history of nephritis: A rise in Pr/Cr of >0.5 over the prior 3-6 months prior to 
screening. 
4. History of severe gastrointestinal narrowing or strictures. 
5. Medically confirmed history of diverticulitis or chronic, ulcerative lower gastrointestinal (GI) disease such as 
Crohn’s disease, ulcerative colitis, or other symptomatic, lower GI conditions that might predispose a participant 
to perforations. 
6. History of thrombosis, pulmonary embolism, or antiphospholipid syndrome. 
7. History of any one of the following anti-phospholipid antibodies: 
a. Positive lupus anticoagulant test, or  
b. Anti-β2-glycoprotein I IgG ELISA titer ≥ 40 GPL, or  
c. Anti-cardiolipin IgG ELISA titer ≥ 40 GPL.   
8. History of chronic pulmonary disease requiring supplemental oxygen including chronic obstructive pulmonary 
disease (COPD) requiring chronic treatment, interstitial lung disease (ILD) requiring immunosuppressive therapy, 
and asthma requiring chronic steroid (other than inhaled steroid) or biologic therapy. 
9. History of moderate to severe atherosclerotic cardiovascular disease as evidenced by prior coronary artery 
bypass surgery, coronary artery stent placement, myocardial infarction, symptomatic carotid arterial disease, 
peripheral vascular disease, abdominal aortic aneurysm; or angina within the past 8 weeks prior to Visit 1 (Day 
0).  
10. History of keloid scarring. 
11. History of any lymphoproliferative disorder or other malignancy with the exception of successfully treated or 
excised basal cell or squamous cell skin cancer or cervical cancer in situ. 
12. Other autoimmune diseases likely to require immunosuppression. 
13. Any of the following lab results at screening: 
a. Hemoglobin <9.5 g/dL 
b. White Blood Cell count <3.5 x 109/L 


Autoimmunity Centers of Excellence 
Confidential 
Page 21 of 52 
ALE11 
Version 7.0 
October 25, 2023 
c. Absolute Neutrophil count <1.2 x 109/L 
d. Platelet count <120 x 109/L 
e. Absolute Lymphocyte count <0.75 x 109/L 
f. 
Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 1.5 × the upper limit of normal 
(ULN) 
g. Total bilirubin > ULN 
h. Estimated glomerular filtration rate [GFR] <60mL/min/1.73 m2 
i. 
Triglycerides ≥ 300 mg/dL (fasting not required) 
j. 
Total Cholesterol ≥ 240 mg/dL (fasting not required). 
14. Major surgery < 8 weeks prior to Visit 1 (Day 0). 
15. Hospitalized for serious infection < 4 weeks prior to Visit 1 (Day 0). 
16. Chronic infections other than chronic or intermittent uncomplicated urinary tract infections (including but not 
limited to tuberculosis (TB), chronic pyelonephritis, osteomyelitis). 
17. Presumed or documented COVID-19 infection within 30 days prior to Visit 1 (Day 0). 
18. Recent (within one month prior to screening) close contact with a person who has active TB infection.  
19. History of untreated active or latent TB infection.  
20. History of incompletely treated active or latent TB infection unless at least one month of treatment has been 
completed prior to screening. 
21. Positive Interferon-Gamma Release Assay (IGRA) or positive purified protein derivative tuberculin skin test (PPD) 
(> 5mm induration) at screening.  
22. An indeterminate IGRA at screening unless followed by a subsequent negative IGRA or negative PPD. 
23. History of human immunodeficiency virus (HIV). 
24. A positive test for HIV antigen/antibody or nucleic acid test (NAT) at screening. 
25. History of a hepatitis B infection. 
26. A positive test for hepatitis B surface antigen or hepatitis B core antibody at screening. 
27. History of a hepatitis C infection. 
28. A positive test for hepatitis C antibody (regardless of whether hepatitis C RNA levels are undetectable) at 
screening. 
29. History of recurrent (more than one episode) herpes zoster, one or more episodes of any of the following: 
herpes zoster ophthalmicus, or disseminated herpes zoster, or disseminated herpes simplex. 
30. Current, recent (< 4 weeks prior to Visit 1 (Day 0)) or chronic use of antibiotic medication, except for suppression 
of chronic/recurrent urinary tract infection, which is allowed. 
31. Simultaneous use of more than one of the following: leflunomide, methotrexate and MMF. 
32. Any of the following active medications (oral or parenteral): cyclosporine, voclosporin, cyclophosphamide, 
tacrolimus, rituximab or other anti-CD20s, or any other investigational or marketed biologic with 
immunomodulatory properties within a year prior to Visit 1 (Day 0). 
33. Any of the following medications (oral or parenteral): azathioprine or belimumab within 3 months prior to Visit 1 
(Day 0). 
34. Any prior treatment with cell-depleting therapies other than anti-CD20s including but not limited to CAMPATH, 
anti-CD4, anti-CD5, anti-CD3, anti-CD19 products. 
35. Intravenous or intramuscular corticosteroids within 2 weeks prior to Visit 1 (Day 0). 
36. Treatment with any investigational agent ≤ 4 weeks or ≤ 5 half-lives of the investigational drug prior to Visit 1 
(Day 0), whichever is longer. 
37. Treatment with more than one dose of ketoconazole within one week of screening. 


Autoimmunity Centers of Excellence 
Confidential 
Page 22 of 52 
ALE11 
Version 7.0 
October 25, 2023 
38. Any prior treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation. 
39. Vaccinated or exposed by close contact, e.g., within a household, to a live/attenuated vaccine ≤ 6 weeks prior to 
Visit 1 (Day 0); or is expected to be vaccinated or to have household exposure to these vaccines during 
treatment or during the 6 weeks following discontinuation of study medication. 
40. Received a non-live vaccine ≤ 2 weeks prior to initiation of study drug, or unwillingness of a participant to delay 
non-live vaccination until 1 month after completion of study therapy. 
41. Pregnant or breastfeeding females. 
42. History of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of 
study drug. 
43. Past or current medical or psychiatric conditions or findings from physical examination or laboratory testing that 
are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the 
study, may interfere with the participant’s ability to comply with study requirements or that may impact the 
quality or interpretation of the data obtained from the study. 
5. Known and Potential Risks and Benefits to Participants 
5.1. Risks of Tofacitinib as cited in US Package Insert 
The following are considered important risks or potential risks identified in the United States Prescribing 
Information (USPI) for XELJANZ®(tofacitinib) and XELJANZ® XR (tofacitinib)[20]: 
1. Serious infections: Tofacitinib increases the risk of serious infections leading to hospitalization or death, 
including TB and bacterial, invasive fungal, viral, and other opportunistic infections. The most common serious 
infections reported include pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and 
appendicitis. Among opportunistic infections, TB and other mycobacterial infections, cryptococcosis, 
histoplasmosis, esophageal candidiasis, pneumocystsis, multidermatomal herpes zoster, cytomegalovirus 
infections, BK virus infection, and listeriosis have been reported. In addition, disseminated infections have been 
reported, and were often associated with concurrent use of immunomodulating agents such as methotrexate 
or corticosteroids.  Other serious infections that have not been reported in clinical studies may also occur.  
 
2. Mortality: In rheumatoid arthritis (RA), individuals with at least one cardiovascular risk factor had a higher risk 
of all-cause mortality including sudden cardiovascular death. 
3. Malignancy and lymphoproliferative disorders: In rheumatoid arthritis, higher rates of malignancies (excluding 
non-melanoma skin cancer) were observed, particularly among current and past smokers. Risks and benefits of 
treatment should be weighed prior to initiating therapy in individuals with a known malignancy other than a 
successfully treated non-melanoma skin cancer.  
4. Major Adverse Cardiovascular Events (MACE): RA patients 50 years of age and older with at least one 
cardiovascular risk factor had a higher rate of MACE defined as cardiovascular death, non-fatal myocardial 
infarction (MI) and non-fatal stroke. Risks and benefits of treatment should be weighed prior to initiating or 
continuing therapy, particularly in patients who are current or past smokers and patients with other 
cardiovascular risk factors. 
5. Thrombosis: Thrombosis, including pulmonary embolism, deep venous thrombosis and arterial thrombosis have 
occurred. RA patients 50 years of age and older with at least one cardiovascular risk factor had an observed 


Autoimmunity Centers of Excellence 
Confidential 
Page 23 of 52 
ALE11 
Version 7.0 
October 25, 2023 
increase in incidence of these events, many of which were serious and some resulting in death. Tofacitinib 
should be avoided in patients who may be at increased risk of thrombosis. 
6. Gastrointestinal perforations: Gastrointestinal perforations have been reported. Caution is warranted in 
individuals who may be at increased risk for gastrointestinal perforation (e.g., those with a history of 
diverticulitis or taking Non-Steroidal Anti-Inflammatory Drugs (NSAIDs).  
7. Hypersensitivity: Hypersensitivity reactions such as angioedema and urticaria that may reflect drug 
hypersensitivity have been observed including some serious events. 
8. Laboratory Abnormalities: 
Lymphocyte abnormalities: Tofacitinib has been associated with a gradual decrease in mean absolute 
lymphocyte counts of approximately 10% over 12 months of therapy. Lymphocyte counts less than 500 
cells/mm were associated with an increased incidence of treated and serious infections. 
Neutropenia: Tofacitinib has been associated with an increased incidence of neutropenia (less than 2000 
cells/mm). 
Anemia: Avoid initiation of tofacitinib in individuals with low hemoglobin level (i.e., < 9 g/dL). 
Liver enzyme elevations: Tofacitinib has been associated with an increased incidence of liver enzyme elevation. 
Most of these abnormalities occurred in studies with background Disease-Modifying Anti-Rheumatic Drugs 
(DMARDs) (primarily methotrexate) therapy. 
Lipid elevations: Tofacitinib has been associated with dose-dependent increases in lipid parameters including 
total cholesterol, low density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. 
Maximum effects were generally observed within 6 weeks. There were no clinically relevant changes in 
LDL/HDL cholesterol ratios. The effect of these lipid parameter elevations on cardiovascular morbidity and 
mortality has not been determined. 
9. Gastrointestinal obstruction: As with any other non-deformable material, caution should be used when 
administering tofacitinib to individuals with preexisting severe gastrointestinal narrowing (pathologic or 
iatrogenic). There have been rare reports of obstructive symptoms in patients with known strictures in 
association with the ingestion of other drugs utilizing a non-deformable extended-release formulation. 
The following additional considerations are noted in the USPI: 
1. Drug interactions:   
 
Strong CYP3A4 inhibitors increase exposure to tofacitinib. Participants taking ketoconazole are excluded 
from this study.  
2. Co-administration with biologic DMARDs or potent immunosuppressive drugs such as azathioprine or 
cyclosporine is not recommended.  
3. Pregnancy, Lactation, and Reproductive potential:  
 
Available data in pregnant women are insufficient to establish a drug associated risk of major birth defects, 
miscarriage or adverse maternal or fetal outcomes. Feticidal and teratogenic effects were noted in animal 
reproduction studies. 


Autoimmunity Centers of Excellence 
Confidential 
Page 24 of 52 
ALE11 
Version 7.0 
October 25, 2023 
 
There are no data on the presence of tofacitinib in human milk, the effects on a breastfed infant, or the 
effects on milk production. Tofacitinib is present in the milk of lactating rats; it is likely that the drug will be 
present in human milk. 
 
Pregnancy planning and prevention is recommended for females of reproductive potential and is planned 
for this study. 
4. Vaccinations: Avoid use of live vaccines concurrently with tofacitinib. The interval between live vaccinations 
and initiation of tofacitinib therapy should be in accordance with current vaccination guidelines regarding 
immunosuppressive agents.  
5. Hepatic impairment: Tofacitinib has not been studied in individuals with severe hepatic impairment and its use 
is not recommended. In studies of individuals with moderate hepatic impairment, tofacitinib blood 
concentration than is higher than individuals with normal hepatic function. Higher blood concentrations may 
increase the risk of some adverse reactions. In addition, the safety and efficacy of tofacitinib have not been 
studied in patients with positive hepatitis B virus or hepatitis C virus serology. 
6. Renal impairment: In individuals with moderate or severe renal impairment, tofacitinib blood concentrations 
are higher than in individuals with normal renal function.  
5.2. Risks of Tofacitinib cited in Medical Literature and FDA Drug Safety Communications  
As noted in Section 1.4, Clinical Studies, the clinical experience of using tofacitinib in lupus patients is limited.  A recent 
report of 10 SLE patients with active skin disease who were treated with tofacitinib 5 mg twice daily for varying time 
points of 4 weeks to one year identified two adverse events.  One patient had an outbreak of Herpes Zoster, the other 
experienced alopecia.  It was not reported as to whether these events were considered related to tofacitinib as all 
patients in the study were on combination therapy with seven out of ten on concomitant corticosteroids and seven out 
of ten on concomitant immunosuppressive medications such as mycophenolate mofetil, tacrolimus, or 
methotrexate[21]. Case reports of successful treatment of patients with rheumatoid arthritis and lupus overlap made no 
mention of adverse events[22]. Preliminary reports of a 56-day active treatment phase 1b/2a safety study of tofacitinib 
5 mg twice daily in patients with systemic lupus identified no severe adverse events or opportunistic infections.  Total 
infections were reported in 55% of patients on tofacitinib and 40% of those on placebo[8], and most of these were 
reported as mild upper respiratory infections. 
5.3. Risks of Other Protocol Specified Medications 
Not applicable. 
5.4. Risks of Study Procedures  
1. Storage of skin and blood samples: Specimens will be identified with a participant-specific code number.  
Safeguards are used to protect the risk to participant’s privacy as outlined in Section 17.3, Privacy and 
Confidentiality. 
2. Blood draw: Drawing blood from a vein may cause some discomfort, bleeding, or bruising, and rarely, infection 
or fainting at puncture site.  A total of 210mL (about 7 oz.) of blood will be collected over the course of the 
entire study.  Blood will be drawn by trained persons and sterile technique will be used to minimize the risk of 
infection. 


Autoimmunity Centers of Excellence 
Confidential 
Page 25 of 52 
ALE11 
Version 7.0 
October 25, 2023 
3. Skin biopsy: The risks include discomfort, e.g., pain, pruritus, and/or bruising at the site of biopsy during 
numbing of the skin or after the anesthetic has worn off, and allergic reactions to lidocaine.  A small amount of 
bleeding may occur during the biopsy, and bleeding may be increased in participants taking blood thinners such 
as aspirin or coumadin.  Rarely, biopsy sites may develop a skin infection.  Biopsy sites may also result in small 
scars, and those with a history of scarring after skin trauma may be at increased risk of scarring. 
4. Ultraviolet Light Exposure: Part of this study includes a brief exposure to different doses of UV light (up to 80 
mJ/cm2). The areas exposed are small (about 1 cm2), but there is a risk of some burning sensation in the areas 
exposed.  In addition, it is possible that skin inflammation following the UV light exposure could linger and 
cause a rash. 
5.5. Summary of Potential Benefits 
There is no direct benefit to participants. This is a proof-of-concept study with a short course of study drug.  
Findings from the proposed studies will provide new information regarding the mechanisms of photosensitivity in lupus 
and the potential ways to treat it. The new information generated from this trial may lead to new therapies for CLE and 
SLE.   
6. Investigational Agent /Device/Intervention  
6.1. Investigational Agents     
6.1.1. XELJANZ® XR (tofacitinib) 
XELJANZ® XR (tofacitinib) extended-release tablets, for oral use are formulated with the citrate salt of tofacitinib, a 
JAK inhibitor. Tofacitinib citrate is a white to off-white powder with the following chemical name: (3R,4R)-4-methyl-
3-(methyl-7H-pyrrolo [2,3-d]pyrimidin-4-ylamino)-ß-oxo-1-piperidinepropanenitrile, 2-hydroxy-1,2,3-
propanetricarboxylate (1:1). The solubility of tofacitinib citrate in water is 2.9 mg/mL. Tofacitinib citrate has a 
molecular weight of 504.5 Daltons (or 312.4 Daltons as the tofacitinib free base) and a molecular formula of 
C16H20N6O∙C6H8O7 [20].  
6.1.1.1. 
Formulation, Packaging, and Labeling 
XELJANZ® XR (tofacitinib) will be purchased by the sponsor, DAIT NIAID, Investigational Products 
Procurement Center through DAIT Pharmacy Purchasing Program.  DAIT’s Clinical Product Center under 
contract (EMINENT Services Corporation) will distribute the investigational product and the labels to the 
study site. The site pharmacy will apply the study-specific flag drug label to the bottles before dispensing 
the IP. 
XELJANZ® XR (tofacitinib) is available in 11mg tablets and will be supplied in bottles of 30 tablets.  The 
tablets used for this study are pink, oval, extended-release film-coated tablets with a drilled hole at one end 
of the tablet band and "JKI 11" printed on one side of the tablet. 


Autoimmunity Centers of Excellence 
Confidential 
Page 26 of 52 
ALE11 
Version 7.0 
October 25, 2023 
6.1.1.2. 
Dosage, Preparation, and Administration 
Participants will take one 11 mg tablet by mouth every morning. XELJANZ® XR (tofacitinib) should be stored 
at room temperature, 20°C to 25°C (68°F to 77° F). It is recommended to take the drug with or without 
food. Tofacitinib tablets should be swallowed whole and intact, do not crush, split or chew[20] .  
6.2. Drug Accountability 
Under Title 21 of the Code of Federal Regulations (21CFR §312.62) the investigator will maintain adequate records of the 
disposition of the investigational agent, including the date and quantity of the drug received, to whom the drug was 
dispensed (participant-by-participant accounting), and a detailed accounting of any drug accidentally or deliberately 
destroyed. 
Records for receipt, storage, use, and disposition will be maintained by the study site.  A drug-dispensing log will be kept 
current for each participant.  This log will contain the identification of each participant and the date and quantity of drug 
dispensed. 
All records regarding the disposition of the investigational product will be available for inspection. 
6.3. Assessment of Participant Compliance with Investigational Agent 
Participants will be asked to return to the clinic with their study drug pill bottles and drug accountability diary at Visit 3 
(Day 14), Visit 4 (Day 25), and Visit 5 (Day 26).  Compliance will be evaluated at Visit 4 (Day 25) before initiating 
phototesting (See Section 3.1, Description of Study Design).  Participants will take their last dose of study medication on 
the morning of Visit 5 (Day 26).  At Visit 5 (Day 26), bottles will be collected by site staff, and pills will be counted again.  
Participants who fail to return their pill bottles at Visit 5 will be asked to return the bottles at Visit 6 (Day 40).  
6.4. Toxicity Prevention and Management 
Prevention 
 
Entry criteria and laboratory testing are designed to exclude individuals with identifiable risk factors.  
 
Participants will be informed of the need to be up-to-date with respect to vaccinations per current immunization 
guidelines. They will be asked to confirm their vaccination status with their provider before enrolling in this 
study.  Vaccination of participants with live components is prohibited within the 6 weeks prior to Visit 1 (Day 0), 
during treatment, or during the 6 weeks following discontinuation of study medication. Non-live vaccines should 
be administered at least 2 weeks prior to initiation of study drug and should not be administered during 
treatment or during the one month after completion of study drug.  
 
Concurrent use of drugs that are contradicted with tofacitinib 11 mg per day is prohibited while on study 
treatment (See Section 7.3, Prohibited Medications).  
 
Safety monitoring will serve to monitor for adverse events that require further evaluation and/or treatment. 
Management 
 
Participants will be seen in clinic on Day 14, approximately 2 weeks after starting study drug, to evaluate signs 
and symptoms and screen for possible adverse events. 
 
Participants will be instructed to call the study coordinator if signs or symptoms of an infection occur during the 
course of the study.  


Autoimmunity Centers of Excellence 
Confidential 
Page 27 of 52 
ALE11 
Version 7.0 
October 25, 2023 
 
Prior to biopsies, participants will be asked about allergies to local anesthetics and solutions used to prepare the 
biopsy site.  A stitch will be used to close the skin biopsy site to minimize the risk of infection and scar formation. 
Biopsies will be performed using sterile techniques by trained staff, and participants will be provided with 
wound care instructions to minimize the risk of infection. 
6.5. Discontinuation/Suspension of Investigational Agent 
6.5.1. Permanent Discontinuation of Investigational Agent 
Participants MUST permanently discontinue tofacitinib for any of the following reasons:  
1. The participant elects to withdraw consent for study treatment.  
2. The participant loses the ability to freely provide consent through imprisonment or involuntary commitment for 
treatment of a psychiatric condition. 
3. The participant becomes pregnant.  
4. The participant experiences anaphylaxis or a Grade 3 or higher allergic reaction.  
5. The participant develops a malignancy excluding basal cell or squamous cell skin cancer or cervical cancer in situ. 
6. The participant experiences a grade 2 or higher thromboembolic event. 
7. A participant is found to have ALT or AST > 3X ULN and total bilirubin > 2X ULN (Hy’s Law).  
If a participant prematurely discontinues study therapy, all subsequent study visits will be cancelled with the 
exception of Visit 6 (Day 40). The participant will be asked to return for an in-person safety follow-up Visit 6 (Day 
40) if the safety event that led to the permanent discontinuation of study treatment was related to study 
participation. The participant will be asked to participate in a virtual or telephone safety follow-up Visit 6 (Day 40) if 
the discontinuation of study treatment was not due to an adverse event related to study participation. See Table 
8.2, Schedule of Events, for more detail. 
6.5.2. Temporary Suspension of Investigational Agent 
Participants MUST temporarily suspend tofacitinib for any of the following reasons:  
1. The participant experiences a clinical adverse event, laboratory abnormality, or intercurrent illness which, in the 
opinion of the investigator, indicates that continued treatment with study drug is not in the best interest of the 
participant.  
2. The participant develops a SAE as defined in Section 12.2.4, Serious Adverse Events. 
3. The participant develops any grade 2 or higher infection.  
4. The participant is diagnosed with an active SARS-CoV-2 (COVID-19) infection, confirmed by PCR or alternative 
viral test according to CDC guidance, independent of symptoms or grade of infection. 
5. The participant develops a fever >101oF. 
6. The participant requires an increase in dose of a permitted background lupus medication as defined in Section 
7.1.2, Other Permitted Concomitant Medications. 
7. If a participant is found to have any of the following lab values (from either unscheduled clinic visits or 
evaluations outside this study): 
 
Lymphocyte count <0.50 x 109/L  


Autoimmunity Centers of Excellence 
Confidential 
Page 28 of 52 
ALE11 
Version 7.0 
October 25, 2023 
 
Absolute neutrophil count (ANC) <1.0 x 109/L  
 
Hemoglobin < 8.0 g/dL or a decrease > 2 g/dL from Visit 1 (Day 0). 
6.6. Resumption of Investigational Product 
Tofacitinib should be taken as prescribed, unless a participant has an event that requires premature discontinuation or 
temporary suspension, as outlined in Section 6.5, Discontinuation/Suspension of Investigational Agent. If a participant 
inadvertently misses one to seven consecutive doses, the participant should resume tofacitinib as soon as possible. If a 
participant is required to temporarily suspend tofacitinib as outlined in 6.5.2, Temporary Suspension of Investigational 
Agent, the participant may resume tofacitinib once the event leading to dose suspension resolves and/or stabilizes, 
provided visits 4 and 5 will occur within 12 weeks after the participant’s Visit 1 (Day 0) and the investigator feels 
resumption of tofacitinib is appropriate.  
In order to achieve the study drug compliance criteria, as described in Section 8.5.5, Research Assessments, one 
additional bottle of tofacitinib may be dispensed. If it is necessary to start a new 25-day course of tofacitinib (e.g. 
substantial study therapy non-adherence or suspension of study therapy for 8 or more consecutive days), the participant 
must undergo a Restart Visit and meet all entry criteria listed in Sections 4.2 Inclusion Criteria and 4.3 Exclusion Criteria, 
prior to starting the new course of tofacitinib. Visits 4 (Day 25) and 5 (Day 26) must occur within 12 weeks after the 
participant’s Visit 1 (Day 0).  A participant may only start a new 25-day course of tofacitinib once. For more information, 
see Table 8.2, Schedule of Events. 
If resumption of tofacitinib is not appropriate, the procedures outlined in 6.5.1, Permanent Discontinuation of 
Investigational Agent, should be followed. 
7. Other Medications 
7.1. Concomitant Medications 
All concomitant medication taken during the study must be recorded with generic name of the medication, indication, 
daily dose, and start and stop dates of administration.  A participant who is receiving an allowed concomitant 
medication for any reason must be on a dose that is considered standard-of-care for the treated indication.  Medications 
taken after informed consent is obtained but before the first dose of study medication will be documented as prior 
medications.  Medications taken after the first dose of study drug has been administered will be documented as 
concomitant medications. 
7.1.1. Protocol-mandated 
There are no protocol-mandated concomitant therapies for participants in this study. 
7.1.2. Other Permitted Concomitant Medications 
Participants are allowed to continue on the following background lupus therapies at permitted doses (as indicated) 
that have been stable for at least 4 weeks prior to Visit 1 (Day 0). Stopping or decreasing doses of these background 
lupus therapies is allowed during the study. Increasing doses of these background lupus therapies (other than PRN 
NSAIDs) is not permitted. See Section 6.5.2, Temporary Suspension of Investigational Agent, for more details. 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 29 of 52 
ALE11 
Version 7.0 
October 25, 2023 
Permitted Lupus Medications1
Permitted doses
Non-steroidal anti-inflammatory drugs 
(NSAIDs including COX 2 inhibitors) 
Daily Dose2 and PRN Usage3
Corticosteroids
≤10 mg daily of prednisone (or equivalent) orally
Quinacrine
≤100 mg daily orally
Hydroxychloroquine
≤400 mg daily orally
Methotrexate
≤25 mg weekly orally or subcutaneously
Leflunomide
≤20 mg daily orally
Mycophenolate mofetil (MMF)
             (or equivalent dose of mycophenolic acid) 
≤3000 mg daily orally
1Topical agents including corticosteroids and tacrolimus are permitted for use except on the area of the skin exposed to UVB.    
  Inhaled corticosteroids are also permitted. 
2Daily doses must remain stable for 1 week prior to UV Treatment and Biopsy. 
3PRN doses are not allowed for 1 week prior to UV treatment and biopsy.  
7.2. Prophylactic Medications 
There are no protocol-mandated prophylactic medications for this study. 
7.3. Prohibited Medications 
Use of tofacitinib in combination with biologic DMARDs or potent immunosuppressants not listed in Section 7.1.2, such 
as azathioprine, voclosporin, and cyclosporine is not allowed. Oral corticosteroids, other than specified in Section 7.1.2, 
and parenteral corticosteroids are prohibited. Methotrexate, leflunomide, or MMF may be continued at stable doses 
indicated in Section 7.1.2, but they may not be used simultaneously with each other. 
No topical therapies of any kind can be used on the area exposed to UVB from the time of the UVB exposure assessment 
until the skin biopsy has been taken the next day. Chemical sunscreens should not be used on the region that will be 
exposed to UVB for at least 12 hours prior to the UVB exposure assessment. Zinc and titanium-based sunscreens may be 
used, but will need to be removed prior to UVB treatment. 
7.4. Rescue Medications 
There are no protocol-mandated rescue medications for this study. 
8. Study Procedures 
8.1. Visit Windows 
With one exception, described below, study visits should take place within the time limits specified in Table 8.1, Visit 
Windows. The designated visit windows for each scheduled visit are also indicated in Table 8.2, Schedule of Events. 
Whenever possible, a rescheduled visit should remain within the designated visit window. The coordinating center 
should be notified if the study procedures for any scheduled visit cannot be performed within the designated window. 


Autoimmunity Centers of Excellence 
Confidential 
Page 30 of 52 
ALE11 
Version 7.0 
October 25, 2023 
Table 8.1. Visit Windows
VISIT
Target Day (window)
Screening Period
(Days -30 to -1)
Visit 1
Day 0
Visit 2 
Day 1, 24 hours after Visit 1 UVB exposure (within 
20-28 hours of Visit 1 UVB exposure) 
Visit 3 
Day 14 (Days 10 to 15)
Visit 4 
Day 25 (Days 21 to 29)
Visit 5 
Day 26, 24 hours after Visit 4 UVB exposure
(within 20-28 hours of Visit 4 UVB exposure) 
Visit 6 
Day 40 (Days 36 to 41)
8.1.1. Exception to Visit Window Rules 
For participants who complete phototesting and the biopsy at Visit 1 (Day 0) and Visit 2 (Day 1), Visit 4 (Day 25) may 
be delayed up to 12 weeks after Visit 1 (Day 0), if necessary.  This may occur if study therapy compliance criteria, as 
described in Section 8.5.5, Research Assessments, have not been met.  
If it is necessary to start a new 25-day course of tofacitinib as described in Section 6.6, Resumption of Investigational 
Product, the participant will have a virtual visit 14 days after reinitiating tofacitinib to assess adverse events. 
8.2. Screening and Enrollment 
The study will be explained in lay terms to each potential research participant. The potential participant will sign an 
informed consent form before undergoing any study procedures.  Once informed consent is obtained, all screening 
procedures, assessments, and laboratory measures to determine participant eligibility will be conducted within a 30-day 
screening window. Eligible participants who meet all entry criteria will proceed with treatment, visits, and assessments 
according to Table 8.2, Schedule of Events.  See Section 8.5, Study Procedures and Assessments for more information on 
individual clinical and research assessments. Participants who do not meet eligibility criteria will be permitted to 
rescreen once. In addition, participants who cannot complete visits 4 (Day 25) and 5 (Day 26) within 12 weeks after the 
participant’s Visit 1 (Day 0) may rescreen and start the study over, if deemed appropriate by the investigator. The 
participant must be off tofacitinib for at least one month prior to the new baseline phototesting and biopsy. 
8.3. Unscheduled Visits  
The investigator may schedule visits in addition to those listed in Table 8.2, Schedule of Events in order to conduct 
evaluations or assessments required to protect the well-being of the participant. If disease activity increases or other 
concerns arise between regularly scheduled visits, participants should be instructed to contact study personnel and may 
be asked to return to the study site for an “unscheduled” visit.   
8.4. Early Termination Visits 
An Early Termination Visit should be requested for participants who withdraw from the study prior to Visit 4 (Day 25).  
See Table 8.2, Schedule of Events, for more information about the assessments that should be conducted at an Early 
Termination Visit.  


Autoimmunity Centers of Excellence 
Confidential 
Page 31 of 52 
ALE11 
Version 7.0 
October 25, 2023 
8.5. Study Procedures and Assessments 
8.5.1. Study Drug 
 
Study drug will be dispensed to eligible participants at Visit 2 (Day 1).  Dosing will begin on day 2 and end on day 
26 prior to the erythema assessment and biopsy at Visit 5 (Day 26). 
 
Study drug compliance will be evaluated at Visit 3 (Day 14).  
 
Study drug compliance will be evaluated at Visit 4 (Day 25) prior to phototesting. 
 
Pill bottles will be collected, and remaining pills will be counted at Visit 5 (Day 26). 
8.5.2. General Assessments 
 
Informed Consent 
 
Demographics: Participants should provide demographic information. In particular, race and ethnicity should be 
self-identified. 
 
Medical History:  Medical history will be performed as part of screening activities and standard medical care. 
The medical history assessment will include current illnesses/conditions and past medical history. 
 
Concomitant Medications: A current list of prescription and over-the-counter medications, supplements, and 
treatments for CLE and SLE will be obtained. Assessment of eligibility should include a review of permitted and 
prohibited medications. The medication, dose, frequency, route, start date, stop date, and indication will be 
captured in the electronic case report form (eCRF). Medications taken 30 days prior to screening through study 
completion or termination should be reported. 
 
Eligibility Review: All entry criteria should be reviewed, and eligibility confirmed prior to scheduling Visit 1 (Day 
0) and again at Visit 1 (Day 0) before drawing blood or phototesting (UVB exposure). 
8.5.3. Clinical Assessments 
 
EULAR/ACR Lupus 2019 [23]: Screening only. 
 
CLASI [24]: This is a validated instrument for evaluating skin inflammation and damage.  
 
SLEDAI-2K: This is a validated instrument for evaluating SLE disease activity. Each component has a weighted 
point value which can sum up to 105. Conditions that are ongoing, recurrent, or new should be assessed 
consistently in relation to a participant’s lupus disease activity. A score ≥ 6 is indicative of active disease.  
 
Physical Examination:  A comprehensive physical examination will be performed at each clinic visit where the 
CLASI and/or SLEDAI 2K are indicated. See Table 8.2, Schedule of Events, for more detail.  
 
Height, Weight, and Vital signs:  Height and weight will only be collected at Screening. Vital signs will include 
pulse, blood pressure, and temperature (Co). Vital signs should be obtained with the participant in a seated 
position prior to taking samples for laboratory testing at applicable study visits. 
 
Fitzpatrick Scale Assessment[25] 
 
Adverse Event Monitoring 


Autoimmunity Centers of Excellence 
Confidential 
Page 32 of 52 
ALE11 
Version 7.0 
October 25, 2023 
8.5.4. Clinical Laboratory Assessments  
Blood and urine for the clinical laboratory assessments listed below will be collected per Table 8.2, Schedule of 
Events. The results will be evaluated for safety by the site investigator. Abnormal tests that meet grading and 
reporting criteria will be reported as adverse events (See Section 12.3.1, Grading Criteria). 
 
Hematology: complete blood count (CBC) including hemoglobin, hematocrit, white cell count, absolute 
neutrophil count, absolute lymphocyte count, and platelet count; and erythrocyte sedimentation rate (ESR). 
 
Blood Chemistry: including lipids (triglycerides and cholesterol), ALT, AST, bilirubin, creatinine, eGFR, C3, C4. 
 
Urinalysis: including protein: creatinine ratio, RBCs, and WBCs.  
 
Serum immunoglobulins: including anti-ds DNA. 
 
Infectious Disease Testing (Screening only): including HIV antigen/antibody or NAT, IGRA or PPD, hepatitis B 
surface antigen, hepatitis B core antibody, and hepatitis C virus (HCV) antibody with HCV RNA (PCR) if antibody 
positive  
 
Pregnancy Testing: serum pregnancy test (Screening), urine pregnancy test (Visit 4 (Day 25) or Early Termination 
Visit). 
8.5.5. Research Assessments  
 
Blood for Serum Biomarkers will be drawn at Visit 1 (Day 0) and Visit 4 (Day 25). 
 
Blood for Cellular and Proteomic studies will be drawn at Visit 1 (Day 0) and Visit 4 (Day 25). 
 
UVB Exposure:  
 
A UV Lamp (Ultralite Enterprises Model 36P10A 10-UNV or equivalent device) will be identified by model 
name and number, and manufacturer at each site.  The same device will be used for all phototesting at each 
site. The UVB dose, based upon the distance from the UV lamp to the participant, will be determined using 
dedicated photometer and probe prior to each use. 
Phototesting will occur at the study site. A photo-barrier template will be placed on non-lesional skin of the 
participant’s exposed lower back/buttock. The template will be placed on the right lower back/buttock for the 
phototest on Visit 1 (Day 0) and on the left lower back/buttock for the Visit 4 (Day 25) test. UV irradiation will be 
applied to the template area via a UV Lamp (Ultralite Enterprises Model 36P10A 10-UNV or equivalent device), 
and every 40 seconds a single template square of the barrier will be covered until all 8 template squares have 
been covered (i.e., total exposure ranges from 10-80 mJ/cm2).  
 
Before initiating phototesting at Visit 4 (Day 25), the participant should meet all the following criteria: 
 
The participant must have completed at least 21 days of IP dosing. 
o For individuals whose Visit 4 (Day 25) has been delayed (See Section 8.1.1, Exception to Visit 
Windows), the 21 days starts from the day IP dosing is resumed. 
 
The participant must confirm that no IP doses have been missed in the prior 7 days. Dosing will be tracked 
on a paper patient diary and in the EDC (Electronic Data Capture) system. 
 
The participant must have taken at least 84% of expected daily doses from the day of the first IP dose. 
Compliance is based on a pill count conducted at Visit 4 (Day 25).   


Autoimmunity Centers of Excellence 
Confidential 
Page 33 of 52 
ALE11 
Version 7.0 
October 25, 2023 
o For individuals whose Visit 4 (Day 25) has been delayed (See Section 8.1.1, Exception to Visit 
Window Rules), compliance should be computed from the day IP dosing is resumed. 
If a participant fails to bring the IP pill bottle(s) back at Visit 4 (Day 25), UVB exposure may proceed during this 
visit. However, site personnel must confirm at least 84% compliance via a visual pill count prior to the erythema 
assessment and biopsy at Visit 5 (Day 26). If 84% compliance is not achieved, participant may resume IP dosing. 
Once the participant has completed appropriate IP dosing, the UVB exposure will be conducted on a site on the 
lower back, above the original. If the participant does not take the final dose of IP the morning of Visit 5 (Day 26), 
the erythema assessment and biopsy will still take place, as long as the participant is compliant with their IP dose 
the 7 days prior to Day 26. 
 
Erythema Assessment:   
At Visit 2 (Day 1) and Visit 5 (Day 26), erythema levels for unexposed skin and each template square of the UVB-
exposed skin will be quantified using a Chroma Meter (Minolta Model CR-400 or equivalent device). To 
determine the MED, first compute the average of all the unexposed skin’s a* (redness) readings and add 2.5.  
The lowest exposure with the site’s average a* (redness) readings at or above this value is the MED.  All skin 
types (except for Fitzpatrick VI) can be expected to show a response within the planned exposure range[26]. 
 
Skin Biopsy:  At the indicated time points, 6mm-diameter punch biopsies of nonlesional skin are planned at 3 
sites as follows: 
1. On Visit 2 (Day 1), 3 biopsy sites on the right buttock include (1) unexposed skin, (2) skin exposed to the 
1x MED, and (3) skin exposed to the UVB dose that is 1 step higher than the 1x MED.  
2. On Visit 5 (Day 26), 3 biopsy sites on the left buttock will be comparable to those taken on Visit 2 (Day 
1), including (1) unexposed skin, (2) skin exposed to the same UVB Dose as the 1x MED from the Visit 2 
(Day 1) assessment, and (3) skin exposed to the UVB dose that is 1 step higher than the 1x MED from the 
Visit 2 (Day 1) assessment.  If the 1x MED from the Visit 2 (Day 1) assessment is at the highest UVB dose 
(80mJ/cm2) or if no erythema is detectable on exposed skin at any dose, then two 4mm biopsies of skin 
exposed the highest UVB dose will be taken at both Visit 2 (Day 1) and Visit 5 (Day 26).  
3. Stitch removal is planned for Visit 3 (Day 14) and Visit 6 (Day 40).  
 
 






Autoimmunity Centers of Excellence 
Confidential 
Page 36 of 52 
ALE11 
Version 7.0 
October 25, 2023 
9. Mechanistic Assays 
Studies on skin biopsies 
1. RNA sequencing to identify changes in inflammatory gene expression before and after UV exposure before and 
after tofacitinib.  
2. TUNEL, 8-hydroxyguanosine, and caspase-3 staining to evaluate for cell death before and after UV exposure 
before and after tofacitinib. 
3. Spatial sequencing to evaluate the inflammatory cell populations before and after UV exposure before and after 
tofacitinib. 
4. Vgll3 localization in biopsies before and after UV exposure before and after tofacitinib to understand how this 
regulator of female bias in autoimmunity is modulated in lupus. 
Studies on blood 
1. Activation of neutrophil NETosis before and after tofacitinib. 
10. Biospecimen Storage 
1. Formalin Fixed, paraffin-embedded (FFPE) skin biopsies collected as part of this study will be retained for up to 
15 years. 
2. Plasma from treated participants will be stored for contribution to approved other collaborative projects. 
3. Peripheral blood mononuclear cells (PBMCs) from studies left over from neutrophil isolation will be frozen and 
stored in LN2 for additional analysis. 
11. Criteria for Participant and Study Completion and Premature Study Termination 
11.1. Participant Completion 
Participants must complete Visits 1 (Day 0), 2 (Day 1), 4 (Day 25), and 5 (Day 26) for inclusion in the final analysis of 
photosensitivity endpoints. 
11.2. Participant Withdrawal Criteria 
Participants may be prematurely withdrawn from the study for the following reasons: 
1. The participant elects to withdraw consent from all future study activities, including follow-up. 
2. The participant is “lost to follow-up” under the following conditions: 
 
An eligible participant who could not be contacted to schedule Visit 1 (Day 0) within the screening 
period. Alternatively, this participant may be re-screened. 
 
A participant who attended Visit 2 (Day 1) but, at some point during follow-up, attempts to reestablish 
contact with the participant fail. Attempts to reconnect should continue until Day 25 at which point “lost 
to follow-up” may be declared.  
 
A participant who attended Visit 1 (Day 0), but misses Visit 2 (Day 1) is allowed to re-screen if contact 
can be reestablished. Otherwise, “lost to follow-up” may be declared. 
3. The participant dies.  
4. The investigator no longer believes participation is in the best interest of the participant.  


Autoimmunity Centers of Excellence 
Confidential 
Page 37 of 52 
ALE11 
Version 7.0 
October 25, 2023 
If a participant withdraws from the study, the participant will be asked to return for a final visit where the 
assessments outlined in the early termination visit in Table 8.2, Schedule of Events, will be performed. No additional 
follow-up will be requested from participants after early study withdrawal. 
11.3. Participant Replacement 
Participants who fail to complete the Visit 4 (Day 25) and Visit 5 (Day 26) photosensitivity and biopsy assessments may 
be replaced according to the following rules, which depend on the reason for withdrawal from the study:  
 
No more than three individuals withdrawn for reasons due to concerns over safety or tolerability of tofacitinib 
may be replaced.  
 
No more than 18 individuals withdrawn for reasons other than safety or tolerability concerns, including 
“external” reasons unrelated to the individual (e.g., study site closed due to COVID-19), may be replaced. 
11.4. Follow-up after Early Study Withdrawal 
Participants who withdraw from the study for any reason will be asked to consent to a final Early Termination Visit to 
complete clinical and safety assessments. See Protocol Section 8.4 Early Termination Visits for more information. 
11.5. Study Stopping Rules 
There are no pre-specified study stopping rules. 
If any of the events described in Section 12.8.2.2, Ad hoc DSMB Reviews occur, an ad hoc DSMB review will occur. After 
review of the data, the Data Safety Motoring Board (DSMB) will make recommendations regarding the study conduct 
and/or continuation.  
12. Safety Monitoring and Reporting 
12.1. Overview 
This section defines the types of safety data that will be collected under this protocol and outlines the procedures for 
appropriately collecting, grading, recording, and reporting those data. Adverse events that are classified as serious 
according to the definition of health authorities must be reported promptly (per Section 12.5, Reporting of Serious 
Adverse Events and Adverse Events) to the sponsor, DAIT/NIAID.  Appropriate notifications will also be made to site 
principal investigators, Institutional Review Boards (IRBs).  
Information in this section complies with International Council for Harmonization (ICH) Guideline E2A: Clinical Safety 
Data Management: Definitions and Standards for Expedited Reporting, ICH Guideline E-6: Guideline for Good Clinical 
Practice, the principles of 21CFR Parts 312 and 320, and applies the standards set forth in the National Cancer Institute 
(NCI), Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0 : Common Terminology Criteria for Adverse 
Events PDF.  
12.2. Definitions 
12.2.1. Adverse Event (AE) 
Any untoward or unfavorable medical occurrence associated with the subject’s participation in the research, whether 
or not considered related to the subject’s participation in the research (modified from the definition of adverse events 
in the 1996 International Conference on Harmonization E-6 Guidelines for Good Clinical Practice) (from OHRP 


Autoimmunity Centers of Excellence 
Confidential 
Page 38 of 52 
ALE11 
Version 7.0 
October 25, 2023 
"Guidance on Reviewing and Reporting Unanticipated Problems Involving Risks to Subjects or Others and Adverse 
Events (1/15/07)" http://www.hhs.gov/ohrp/policy/advevntguid.html#Q2 )  
12.2.2. Suspected Adverse Reaction  
Any adverse event for which there is a reasonable possibility that the investigational drug [or investigational study 
therapy regimen] caused the adverse event. For the purposes of safety reporting, ‘reasonable possibility’ means there 
is evidence to suggest a causal relationship between the drug and the adverse event. A suspected adverse reaction 
(SAR) implies a lesser degree of certainty about causality than adverse reaction, which means any adverse event 
caused by a drug (21 CFR 312.32(a)). 
For this study, a SAR will include any untoward or unfavorable medical occurrence associated with:   
 
Study therapy: tofacitinib 
 
Skin biopsy 
 
UVB exposure 
12.2.3. Unexpected Adverse Event  
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the package insert or is 
not listed at the specificity, severity or rate of occurrence that has been observed; or is not consistent with the risk 
information described in the general investigational plan or elsewhere in the Investigational New Drug (IND). 
12.2.4. Serious Adverse Event  
An adverse event or SAR is considered “serious” if, in the view of either the investigator or DAIT/NIAID, it results in any 
of the following outcomes (21 CFR 312.32(a)): 
1. Death. 
2. A life-threatening event: An AE or SAR is considered “life-threatening” if, in the view of either the investigator or 
DAIT/NIAID, its occurrence places the participant at immediate risk of death. It does not include an AE or SAR 
that, had it occurred in a more severe form, might have caused death.  
3. Inpatient hospitalization or prolongation of existing hospitalization. 
4. Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 
5. Congenital anomaly or birth defect.  
6. Important medical events that may not result in death, be life threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and 
may require medical or surgical intervention to prevent one of the outcomes listed above. 
Elective hospitalizations or hospital admissions for the purpose of conduct of protocol mandated procedures are not 
to be reported as an SAE unless hospitalization is prolonged due to complications.  
12.3. Grading and Attribution of Adverse Events 
12.3.1. Grading Criteria 
The study site will grade the severity of adverse events experienced by the study participants according to the criteria 
set forth in the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) 5.0. This 
document (referred to herein as the NCI-CTCAE manual) provides a common language to describe levels of severity, to 


Autoimmunity Centers of Excellence 
Confidential 
Page 39 of 52 
ALE11 
Version 7.0 
October 25, 2023 
analyze and interpret data, and to articulate the clinical significance of all adverse events. The NCI-CTCAE has been 
reviewed by the Protocol Chair and has been deemed appropriate for the population to be studied in this protocol. 
Adverse events will be graded on a scale from 1 to 5 according to the following standards in the NCI-CTCAE manual: 
Grade 1 = mild adverse event. 
Grade 2 = moderate adverse event. 
Grade 3 = severe or medically significant. 
Grade 4 = life-threatening consequences; urgent intervention indicated. 
Grade 5 = death. 
Events of Grade 2 or higher and all Grade 1 or higher COVID-19 events will be recorded on the appropriate AE eCRF for 
this study according to 12.4, Collection and Recording of Adverse Events. 
For grading an abnormal value or result of a clinical or laboratory evaluation (including, but not limited to, a 
radiograph, an ultrasound, an electrocardiogram etc.), a treatment-emergent adverse event is defined as an increase 
in grade from the last assessment prior to a participant starting treatment, or from the last post-baseline value that 
doesn’t meet grading criteria. Changes in grade from screening to Day 0, Day 1, and treatment initiation (Day 2) will 
also be recorded as adverse events, but are not treatment-emergent. If a specific event or result from a given clinical 
or laboratory evaluation is not included in the NCI-CTCAE manual, then an abnormal result would be considered an 
adverse event if changes in therapy or monitoring are implemented as a result of the event/result. 
Liver function abnormalities will be graded using criteria from NCI-CTCAE version 4.0, defined relative to the ULN as 
follows: 
 
Aspartate aminotransferase [AST] increased 
o Grade 1: > ULN – 3.0x ULN 
o Grade 2: > 3.0x ULN - 5.0x ULN 
o Grade 3: > 5.0x ULN - 20.0x ULN  
o Grade 4: > 20.0x ULN 
 
Alanine aminotransferase [ALT] increased 
o Grade 1: > ULN – 3.0x ULN 
o Grade 2: > 3.0x ULN - 5.0x ULN 
o Grade 3: > 5.0x ULN - 20.0x ULN  
o Grade 4: > 20.0x ULN 
 
Alkaline phosphatase [ALP] increased 
o Grade 1: > ULN – 2.5x ULN 
o Grade 2: > 2.5x ULN - 5.0x ULN 
o Grade 3: > 5.0x ULN - 20.0x ULN  
o Grade 4: > 20.0x ULN 
 
Blood bilirubin increased  
o Grade 1: > ULN – 1.5x ULN 
o Grade 2: > 1.5x ULN - 3.0x ULN 
o Grade 3: > 3.0x ULN - 10.0x ULN  
o Grade 4: > 10.0x ULN  


Autoimmunity Centers of Excellence 
Confidential 
Page 40 of 52 
ALE11 
Version 7.0 
October 25, 2023 
12.3.2. Attribution Definitions 
The relationship, or attribution, of an adverse event to the study therapy regimen or study procedure(s) will initially be 
determined by the site investigator and recorded on the appropriate AE/SAE eCRF.  Final determination of attribution 
for safety reporting will be determined by DAIT/NIAID.  The relationship of an adverse event to study therapy regimen 
or procedures will be determined using the descriptors and definitions provided in Table 12.1.  
For additional information and a printable version of the NCI-CTCAE manual, consult the NCI-CTCAE web site: 
http://ctep.cancer.gov/reporting/ctc.html. 
       
Table 12.1 Attribution of Adverse Events 
Code 
Descriptor 
Relationship (to primary investigational product and/or 
other concurrent mandated study therapy or study 
procedure) 
Unrelated Category 
1 
Not Related 
The adverse event is clearly not related:  there is insufficient 
evidence to suggest a causal relationship. 
 Related Categories 
2 
Possibly 
Related 
The adverse event has a reasonable possibility to be 
related; there is evidence to suggest a causal relationship. 
3 
Related 
The adverse event is clearly related. 
12.4. Collection and Recording of Adverse Events 
12.4.1. Collection Period 
Adverse events will be collected and recorded in EDC from Visit 1 (Day 0), until a participant completes study 
participation or until 30 days after he/she prematurely withdraws or is withdrawn from the study (without 
withdrawing consent). Serious Adverse Events, as defined in Section 12.2.4 Serious Adverse Events, Suspected Adverse 
Reactions, as defined in Section 12.2.2, Suspected Adverse Reactions, and adverse events related to study procedures 
will be collected and recorded in EDC from the time of consent until a participant completes study participation or 
until 30 days after he/she prematurely withdraws or is withdrawn from the study (without withdrawing consent). 
12.4.2. Collecting Adverse Events 
Adverse events (including SAEs) may be discovered through any of these methods: 
 
Observing the participant. 
 
Interviewing the participant [e.g., using a checklist, structured questioning, diary, etc.]. 
 
Receiving an unsolicited complaint from the participant. 
In addition, an abnormal value or result from a clinical or laboratory evaluation can also indicate an adverse event, as 
defined in Section 12.3, Grading and Attribution of Adverse Events. 


Autoimmunity Centers of Excellence 
Confidential 
Page 41 of 52 
ALE11 
Version 7.0 
October 25, 2023 
12.4.3. Recording Adverse Events 
Throughout the study, the investigator will record all adverse events and SAEs as described previously (Section 12.2, 
Definitions) on the appropriate AE/SAE eCRF regardless of the relationship to study therapy regimen or study 
procedure. 
Once recorded, an AE/SAE will be followed until it resolves with or without sequelae, or until the end of study 
participation, or until 30 days after the participant prematurely withdraws or is withdrawn from the study, whichever 
occurs first (without withdrawing consent). 
12.5. Reporting of Serious Adverse Events and Adverse Events 
12.5.1. Reporting of Adverse Events  
This section describes the responsibilities of the site investigator to report AEs to the study sponsor via the DAIT-
SACCC (Division of Allergy, Immunology, and Transplantation Statistical and Clinical Coordinating Center).  
Timely reporting of AEs of NCI-CTCAE Grade 2 and higher and Grade 1 or higher COVID-19 event is required. Unless 
otherwise noted below in Section 12.5.2 for SAEs, AEs must be recorded on the AE/SAE eCRF within five (5) days of 
discovery of the event. Whenever possible, a diagnosis should be provided, rather than compilation of 
signs/symptoms, with grade of the event dictated by highest grade of the sign/symptom component. 
12.5.2. Reporting of Serious Adverse Events to DAIT/NIAID (Sponsor) 
This section describes the responsibilities of the site investigator to report SAEs to the Study Sponsor (NIAID/DAIT) via 
the AE/SAE eCRF.  Timely reporting of adverse events is required by 21 CFR and ICH E6 guidelines.  
When a site investigator identifies a SAEs, he or she must notify DAIT/NIAID via the DAIT-SACCC within 24 hours 
regardless of the relationship or expectedness. Site investigators are to report these events on the SAE eCRF in 
Electronic Data Capture (EDC). Should EDC become unavailable/ inaccessible, the site investigator should notify 
DAIT/NIAID via the DAIT-SACCC email at Rho_productsafety@rhoworld.com.  This email can serve as the initial 
notification; however, within the next business day the SAE eCRF must be completed. 
All requested information on the SAE eCRF should be provided. Unavailable details of the event at time of initial report 
should not delay submission of known information. The initial report should include at a minimum: AE term, 
relationship to tofacitinib, and reason why event is serious (per definitions). Supplementary Case Report Form (CRF) 
pages including medical history, concomitant medications, demographics, study drug administration, and death must 
be provided. As additional details become available, the SAE eCRF should be updated and submitted. With each 
iteration of the form, the investigator (or designated sub-investigator) must sign the form electronically. 
For additional information regarding SAE reporting, contact Rho Product Safety (DAIT-SACCC):  
Rho Product Safety  
 
 
  
  
 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 42 of 52 
ALE11 
Version 7.0 
October 25, 2023 
12.5.3. Reporting to FDA 
This clinical study has been granted exemption from investigational new drug application (IND) regulations by the FDA 
in accordance with 21 CFR 312.2(b) of the regulations, therefore, AEs will not be reported to the FDA by the study 
sponsor (NIAID). 
12.5.4. Reporting of Adverse Events to IRBs/IECs 
In this multi-site study, the investigators shall report adverse events, including expedited reports, in a timely fashion to 
their respective IRB/IEC in accordance with applicable regulations and guidelines.  
12.6. Pregnancy Reporting 
The investigator shall be informed immediately of any pregnancy in a study participant or a partner of a study 
participant.  A pregnant study participant shall be instructed to stop taking study medication immediately. A study 
participant whose partner is pregnant shall be advised to inform the partner’s obstetrician about the trial. The 
investigator shall counsel the participant and discuss the risks of continuing with the pregnancy and the possible effects 
on the fetus. Monitoring of the pregnant participant shall continue until the conclusion of the pregnancy. Additionally, 
pregnant participants and partners should be given information about Mother to Baby. The current patient information 
fact sheet on tofacitinib can be found at the following link: https://mothertobaby.org/fact-sheets/tofacitinib-pregnancy/ 
The investigator shall report to DAIT/NIAID via the DAIT-Statistical and Clinical Coordinating Center (SACCC) within 1 
business day of becoming aware of the event using the Pregnancy eCRF.  All pregnancies in study participants identified 
during the study shall be followed to conclusion and the outcome of each must be reported. Pregnancies in the partners 
of study participants do not have to be followed to conclusion; however, the status of the partner should be reported at 
the last study visit, if known. The Pregnancy eCRF shall be updated and submitted to the DAIT-SACCC when details about 
the outcome are available.  When possible, similar information shall be obtained for a pregnancy occurring in a partner 
of a study participant. 
Information requested about the delivery shall include: 
 
Gestational age at delivery. 
 
Birth weight, length, and head circumference. 
 
Gender. 
 
Appearance, pulse, grimace, activity, and respiration (APGAR) score at 1 minute, 5 minutes, and 24 hours after 
birth, if available. 
 
Any abnormalities. 
All pregnancy complications that result in a congenital abnormality, birth defect, miscarriage, and medically indicated 
abortion - an SAE shall be submitted to the DAIT-SACCC using the SAE reporting procedure described above (Section 
12.5.1, Reporting of Serious Adverse Events to DAIT/NIAID).  
12.7. Reporting of Other Safety Information 
An investigator shall promptly notify DAIT/NIAID via the DAIT-SACCC when an “unanticipated problem involving risks to 
participants or others” is identified, which is not otherwise reportable as an adverse event. 


Autoimmunity Centers of Excellence 
Confidential 
Page 43 of 52 
ALE11 
Version 7.0 
October 25, 2023 
12.8. Review of Safety Information 
12.8.1. Medical Monitor Review 
The DAIT/NIAID Medical Monitor shall receive monthly reports from the DAIT-SACCC compiling new and accumulating 
information on AEs, SAEs, and pregnancies recorded by the study site on appropriate eCRFs. 
In addition, the Medical Monitor shall review and make decisions on the disposition of the SAE and pregnancy reports 
received by the DAIT-SACCC (See Sections 12.5.1, Reporting of Serious Adverse Events to DAIT/NIAID, and 12.6, 
Pregnancy Reporting).   
12.8.2. Data Safety and Monitoring Board Review  
12.8.2.1. Planned DSMB Reviews  
The progress of the study will be monitored by the NIAID Data and Safety Monitoring Board (DSMB). The 
DSMB shall review safety data at least yearly during planned DSMB Data Review Meetings. Data for the 
planned safety reviews will include, at a minimum, a listing of all reported AEs and SAEs.  The DSMB will also 
be informed of any Expedited Safety Reports during planned safety reviews. 
In addition, the DSMB will be notified of any notable impacts on the study due to COVID-19 (See Section 
3.1.1, Considerations Regarding COVID-19.) 
12.8.2.2. Ad hoc DSMB Reviews  
In addition to the pre-scheduled data reviews and planned safety monitoring, the DSMB may be called upon 
for ad hoc reviews. The DSMB will review any event that potentially impacts safety at the request of the 
protocol chair or DAIT/NIAID. In addition, the following events will trigger an ad hoc comprehensive DSMB 
Safety Review:  
 
Any death considered possibly or definitely related to study treatment or procedures. 
 
The occurrence in 2 participants of Grade 3 or higher AEs or SAEs with the same MedDRA preferred 
terms considered at least possibly related to study treatment or procedures. 
 
The occurrence in 2 participants of Grade 3 or higher infections. 
 
Any grade 2 or higher thromboembolic event. 
After review of the data, the DSMB will make recommendations regarding study conduct and/or 
continuation. 
12.8.2.2.1. Temporary Suspension of Tofacitinib Dosing for ad hoc DSMB Safety Review  
If a triggering event occurs and an ad hoc DSMB Safety Review is required (Section 12.8.2.2, Ad hoc 
DSMB Reviews), then a temporary halt in initiating dosage for new enrollees will be implemented. 
Participants on study treatment will continue as planned. If two weeks has elapsed and the ad-hoc 
DSMB has not met, then no new participants will be consented or enrolled until after the DSMB 
completes review of the safety data. 


Autoimmunity Centers of Excellence 
Confidential 
Page 44 of 52 
ALE11 
Version 7.0 
October 25, 2023 
13. Statistical Considerations and Analytical Plan 
13.1. Overview 
This is a single-arm multi-site proof-of-concept study in which participants with CLE will undergo 25 days of treatment 
with tofacitinib (11 mg daily PO).  The primary objective is to determine the impact of tofacitinib on photosensitivity 
parameters, including UVB-mediated cutaneous apoptosis, UVB-mediated inflammatory gene transcription, and MED in 
response to UVB exposure. The study will also evaluate changes in clinical endpoints and safety. 
13.2. Endpoints 
Primary and secondary endpoints are listed in Sections 3.2, Primary Endpoint and 3.3, Secondary Endpoints.   
 
13.3. Measures to Minimize Bias 
This study includes well-defined entry criteria to ensure the target population is correctly identified. Although the study 
has a single open-label arm, the photosensitivity parameters, which are key to evaluating the primary objective, are all 
objectively measured and not subject to participant or investigator bias.  To minimize the potential threat to study 
integrity by loss of participants between the first and second phototests/biopsies, assessments are kept to minimum, 
and attention will be paid to participant well-being during and after procedures. 
13.4. Analysis Plan 
13.4.1. Analysis Populations 
The Safety Sample (SS) population includes all participants who receive any amount of tofacitinib.  
The Per Protocol 1 (PP1) population includes all participants who receive any amount of tofacitinib and who 
complete phototests and skin biopsies at both baseline (Visits 1 and 2) and post-treatment (Visits 4 and 5) time 
points. Only individuals who complete at least 21 days of IP dosing will have the post-treatment phototest. The 
primary objective of this proof-of-concept study cannot be evaluated in individuals who do not have data at both 
pre- and post-treatment time points. 
The Per Protocol 2 (PP2) population includes all PP1 participants with no protocol deviations that would impact 
photo sensitivity assessments. The reported major deviations will be reviewed during a masked data review to 
determine which participants should be excluded from the PP2 population. 
13.4.2. Primary Analysis of Primary Endpoint 
The primary endpoint is change in percentage of UVB-induced apoptotic epidermal cells from Visit 2 (Day 1) (pre-
treatment) to Visit 5 (Day 26) (post-treatment). Percentage of UVB-induced apoptotic cells (AUVB) is defined as the 
number of TUNEL positive cells in the epidermis divided by the number of nuclei in that high powered field. The 
percentage of UVB-induced apoptotic cells at a visit is defined as the difference between the percentage of apoptotic 
epidermal cells in the biopsy exposed at the MED (ADay1MED) and percentage of apoptotic epidermal cells in the 
unexposed biopsy (Aunexposed), for both biopsies taken at the same visit.  The change in percentage of UVB-induced 
apoptotic epidermal cells will be computed as follows for each individual in the study: 
Aୈୟ୷ ଵ
୙୚୆= Aୈୟ୷ ଵ
ୈୟ୷ଵ୑୉ୈ−Aୈୟ୷ ଵ
ୈୟ୷ ଵ ୳୬ୣ୶୮୭ୱୣୢ 
Aୈୟ୷ ଶ଺
୙୚୆
= Aୈୟ୷ ଶ଺
ୈୟ୷ଵ୑୉ୈ−Aୈୟ୷ ଶ଺
ୈୟ୷ ଶ଺ ୳୬ୣ୶୮୭ୱୣୢ 
change in A୙୚୆= Aୈୟ୷ ଶ଺
୙୚୆
−Aୈୟ୷ ଵ
୙୚୆ 


Autoimmunity Centers of Excellence 
Confidential 
Page 45 of 52 
ALE11 
Version 7.0 
October 25, 2023 
The null and alternative hypotheses for the primary analysis of the primary endpoint are: 
H0:  Mean change in A୙୚୆= 0  
HA: Mean change in A୙୚୆≠0 
The statistical hypotheses outlined above for the mean change in AUVB will be evaluated in the PP1 population using a 
two-sided Wilcoxon signed-rank test at a Type 1 error rate of 0.05.   
13.4.3. Supportive Analyses of the Primary Endpoint 
The primary hypothesis will also be evaluated in the PP2 population. In addition, depending on findings, exploratory 
analyses may be considered post hoc.   
13.4.4. Analyses of Secondary Endpoints  
The PP1 population will be used for evaluation of photosensitivity and disease activity measures.  For each secondary 
endpoint, the null hypothesis is that there is no change in the parameter of interest from pre- to post-treatment time 
points. All secondary inferential analyses are considered supportive; p-values will be presented without adjustment 
for multiple comparisons.  
Analysis of secondary safety endpoints will be conducted using the safety population.  
13.4.4.1. Photosensitivity parameters 
The following analyses of these secondary endpoints will support the primary objective to evaluate the 
impact of tofacitinib on photosensitivity parameters. 
 
Change in MED due to UVB from Visit 2 (Day 1) to Visit 5 (Day 26): MED is an ordinal endpoint. Shifts 
in MED levels from pre- to post-treatment will be evaluated using the McNemar-Bowker test for 
symmetry. 
 
Change in UVB-induced expression of inflammatory genes in skin from Visit 2 (Day 1) to Visit 5 (Day 
26), based on enumeration of RNA transcripts:  The mean change will be evaluated using a two-sided 
Wilcoxon signed-rank test.  
13.4.4.2. Disease activity 
 
Changes in CLASI activity score, CLASI damage scores, and SLEDAI-2K total scores from Visit 1 (Day 0) 
to Visit 4 (Day 25): For each endpoint, the mean change will be evaluated using a two-sided Wilcoxon 
signed-rank test. 
13.4.4.3. Safety  
 
Clinical laboratory values will be summarized using descriptive statistics.  In addition, individuals with a 
laboratory value that increases during the study by 1 or more severity grades per NCI-CTCAE will be 
identified and tabulated. 
 
Treatment-emergent AEs and SAEs will be summarized by severity, by relationship to study drug, and 
by MedDRA Organ Class and Preferred Term.   




Autoimmunity Centers of Excellence 
Confidential 
Page 47 of 52 
ALE11 
Version 7.0 
October 25, 2023 
power is ≥93% for a mean change in AUVB of at least 20 percentage points under all four distributions (=0.05, two-sided, 
Wilcoxon signed-rank test). Power is ≥80% under all 4 distributions for a mean change in AUVB of at least 21.4 percentage 
points as long as the SD≤ 20%.  If the underlying SD is 30%, the upper 80% confidence limit from Table 13.1, the design 
has at least 80% power to detect a change of at least 30 percentage points under the uniform, logistic, and double 
exponential distributions, and 32.1 percentage points under the normal distribution. Power was computed using PASS 
version 15. 
 
Figure 2. Power for 10 paired samples (pre and post treatment) under different distribution assumptions 
All participants completing Visit 5 (Day 26) skin biopsy will be included in the primary analysis of the primary endpoint. 
For the primary analysis, there will be no missing data; participants who cannot complete the second biopsy will be 
replaced. As such, missing data does not impact the power/sample size considerations, but attrition will be considered 
when evaluating generalizability of the results. 
14. Identification and Access to Source Data 
14.1. Source Data 
Source documents and source data are considered to be the original documentation where participant information, 
visits consultations, examinations and other information are recorded.   Documentation of source data is necessary for 
the reconstruction, evaluation, and validation of clinical findings, observations, and other activities during a clinical trial.  


Autoimmunity Centers of Excellence 
Confidential 
Page 48 of 52 
ALE11 
Version 7.0 
October 25, 2023 
14.2. Access to Source Data 
The site investigators and site staff will make all source data available to the DAIT/NIAID, NIAID representatives, agents, 
employees, contractors, and other persons assisting in conducting, monitoring, or analyzing the study, as well as to 
relevant health authorities. Authorized representatives as noted above are bound to maintain the strict confidentiality 
of medical and research information that may be linked to identified individuals. 
15. Quality Assurance and Quality Control 
The principal investigator is required to keep accurate records to ensure that the conduct of the study is fully 
documented. The principal investigator is required to ensure that all eCRFs are completed for every participant entered 
in the trial. The period of record retention should be consistent with the record retention policies of the sponsoring 
agency or applicable regulatory agencies. However, in certain instances, documents should be retained for a longer 
period if required by the applicable regulatory agency or by the National Institutes of Health. 
Data will be obtained from a variety of sources including, but not limited to laboratory notebooks, automated 
instrument output files, and clinical participant charts. Data from these source materials will be transmitted to the DAIT 
data center via one of two mechanisms. Data collected electronically at central laboratories will be transferred 
electronically directly from the laboratory to the DAIT data center using standard secure data transfer procedures. Data 
collected at the clinical site will be transmitted to the DAIT data center using an internet-based remote data entry 
system. Clinical site personnel use an internet browser to key data into eCRFs; each CRF page is submitted to the clinical 
database electronically as the page is completed. Univariate data validation tests are performed as the data are keyed. 
The clinical database is backed up nightly; backup tapes are saved in a secure, off-site location. At any time, authorized 
site personnel may log in to the remote data entry system, review and correct previously entered data, or key additional 
data. The data will be further validated per the study data validation plan via a series of computerized and manual edit 
checks, and all relevant data queries will be raised and resolved on an ongoing basis. Complete, clean data will be frozen 
to prevent further inadvertent modifications. All discrepancies will be reviewed, and any resulting queries will be 
resolved with the investigators and amended in the database. All elements of data entry (i.e., time, date, verbatim text, 
and the person performing the data entry) will be recorded in an electronic audit trail to allow all data changes in the 
database to be monitored and maintained in accordance with federal regulations.   
Monitors are responsible for regular inspection of the conduct of the trial, for verifying adherence to the protocol, and 
for confirming the completeness, consistency, and accuracy of all documented data.  
Monitors will periodically visit the participating clinical site and audit the source documents in order to validate the data 
in the central database. Data will be provided using the participant’s screening or enrollment number, the DAIT data 
center will not collect personally identifying information such as the participant’s name or social security number. 
Participants will provide demographic information such as race, ethnicity, and birth date. 
Data collected by the DAIT data center will be held in the strictest confidence and are protected from access that could 
reveal personally identifying information about any participant in the trial.  


Autoimmunity Centers of Excellence 
Confidential 
Page 49 of 52 
ALE11 
Version 7.0 
October 25, 2023 
16. Protocol Deviations 
16.1. Protocol Deviation Definitions 
Protocol Deviation – The investigators and site staff will conduct the study in accordance with the protocol; no 
deviations from the protocol are permitted.  Any change, divergence, or departure from the study design or procedures 
constitutes a protocol deviation.  As a result of any deviation, corrective actions will be developed by the site and 
implemented promptly. 
Major Protocol Deviation (Protocol Violation) – A Protocol Violation is a deviation from the IRB approved protocol that 
may affect the participant's rights, safety, or well-being and/or the completeness, accuracy, and reliability of the study 
data.  In addition, protocol violations include willful or knowing breaches of human subject protection regulations, or 
policies, any action that is inconsistent with the NIH Human Research Protection Program’s research, medical, and 
ethical principles, and a serious or continuing noncompliance with federal, state, local or institutional human subject 
protection regulations, policies, or procedures.  
Non-Major Protocol Deviation – A non-major protocol deviation is any change, divergence, or departure from the study 
design or procedures of a research protocol that does not have a major impact on the participant's rights, safety or well-
being, or the completeness, accuracy, and reliability of the study data. 
16.2. Reporting and Managing Protocol Deviations 
The study site principal investigator has the responsibility to identify, document and report protocol deviations as 
directed by the DAIT/NIAID.  However, protocol deviations may also be identified during site monitoring visits or during 
other forms of study conduct review.  
When a deviation occurs, corrective actions may be necessary depending on the nature of the deviation. The Principal 
Investigator (PI) and NIAID/DAIT conduct a risk assessment. The PI is responsible for the timely correction and 
documentation of problems identified by study personnel, outside monitors or auditors, or other parties involved in the 
conduct of a study. The depth of Corrective Action/Preventive Action (CAPA) required should match the risk and impact 
on safety of participants and/or the quality of the data. 
Upon determination that a protocol deviation has occurred, the PI/designated study staff will report the deviation 
according to the processes outlined for the study. A major deviation is to be reported within 3 business days and 
reported by the PI to the IRB per IRB reporting requirements. NIAID/DAIT will determine if the deviation is reportable to 
the DSMB, as applicable. 
17. Ethical Considerations and Compliance with Good Clinical Practice 
17.1. Statement of Compliance 
This clinical study will be conducted using good clinical practice (GCP), as delineated in Guidance for Industry: E6 Good 
Clinical Practice Consolidated Guidance, and according to the criteria specified in this study protocol.  Before study 
initiation, the protocol and the informed consent documents will be reviewed and approved by the IRB.  Any 
amendments to the protocol or to the consent materials will also be approved by the IRB before they are implemented. 


Autoimmunity Centers of Excellence 
Confidential 
Page 50 of 52 
ALE11 
Version 7.0 
October 25, 2023 
17.2. Informed Consent Process 
The consent process will provide information about the study to a prospective participant and will allow adequate time 
for review and discussion prior to his/her decision.  The principal investigator or their designee listed on the Investigator 
of Record Agreement will review the consent and answer questions.  The prospective participant will be told that being 
in the trial is voluntary and that he or she may withdraw from the study at any time, for any reason.  All participants (or 
their legally acceptable representative) will read, sign, and date a consent form before undergoing any study 
procedures.  Consent materials will be presented in participants’ primary language. A copy of the signed consent form 
will be given to the participant. 
The consent process will be ongoing.  The consent form will be revised when important new safety information is 
available, the protocol is amended, and/or new information becomes available that may affect participation in the 
study.  
17.3. Privacy and Confidentiality 
A participant’s privacy and confidentiality will be respected throughout the study.  Each participant will be assigned a 
unique identification number and these numbers rather than names will be used to collect, store, and report participant 
information.  The code linking the participant’s identity to the unique identification number will be securely stored a 
password protected, HIPPA compliant shared drive managed by University of Michigan Health Information Technology.  
The only the protocol chair and approved study team members who have completed appropriate human subjects 
research training have access to the drive. Site personnel will not transmit documents containing personal health 
identifiers (PHI) to the NIAID/DAIT or their representatives. 
The study protocol, documentation, data, and all other information generated will be held in strict confidence.  No 
information concerning the study, or the data will be released to any unauthorized third party without prior written 
approval of NIAID/DAIT. 
The study Monitor or other authorized representatives of the NIAID/DAIT may inspect all documents and records 
required to be maintained by the Investigator, including but not limited to, medical records (office, clinic, or hospital) 
and pharmacy records for the participants in this study.  The clinical study site will permit access to such records. 
18. Publication Policy 
The Autoimmunity Centers of Excellence’s policy on the publication of study results will apply to this trial. Authorized 
participants may find details regarding the policy statement on the ADCT internet website at http://www.rhoworld.com. 
 
 
 
 
 


Autoimmunity Centers of Excellence 
Confidential 
Page 51 of 52 
ALE11 
Version 7.0 
October 25, 2023 
19. References 
1. 
Szczech, J., et al., Trigger factors of cutaneous lupus erythematosus: a review of current literature. Lupus, 2017: 
p. 961203317691369. 
2. 
Sanders, C.J., et al., Photosensitivity in patients with lupus erythematosus: a clinical and photobiological study of 
100 patients using a prolonged phototest protocol. Br J Dermatol, 2003. 149(1): p. 131-7. 
3. 
Kuhn, A., J. Wenzel, and H. Weyd, Photosensitivity, Apoptosis, and Cytokines in the Pathogenesis of Lupus 
Erythematosus: a Critical Review. Clinical Reviews in Allergy & Immunology, 2014. 47(2): p. 148-162. 
4. 
Saenz-Corral, C.I., et al., Apoptosis in chronic cutaneous lupus erythematosus, discoid lupus, and lupus profundus. 
Int J Clin Exp Pathol, 2015. 8(6): p. 7260-5. 
5. 
Mahajan, A., M. Herrmann, and L.E. Munoz, Clearance Deficiency and Cell Death Pathways: A Model for the 
Pathogenesis of SLE. Front Immunol, 2016. 7: p. 35. 
6. 
Sarkar, M.K., et al., Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived 
interferon kappa. Ann Rheum Dis, 2018. 77(11): p. 1653-1664. 
7. 
Berthier, C.C., et al., Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical 
Phenotypes. J Clin Med, 2019. 8(8). 
8. 
Hasni, S.A., et al., Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in 
systemic lupus erythematosus. Nat Commun, 2021. 12(1): p. 3391. 
9. 
Bonnardeaux, E. and J.P. Dutz, Oral tofacitinib citrate for recalcitrant cutaneous lupus. JAAD Case Rep, 2022. 20: 
p. 61-64. 
10. 
Elman, S.A., D.R. Mazori, and J.F. Merola, Tofacitinib for refractory chilblain lupus erythematosus. Int J Dermatol, 
2022. 61(4): p. e156-e157. 
11. 
McInnes, I., et al., 06.02 Ex vivo functional comparison of baricitinib and tofacitinib for cytokine signalling in 
human leukocyte subpopulations. 2017, BMJ Publishing Group Ltd. 
12. 
Cohen, S.B., et al., Real-World Evidence to Contextualize Clinical Trial Results and Inform Regulatory Decisions: 
Tofacitinib Modified-Release Once-Daily vs Immediate-Release Twice-Daily for Rheumatoid Arthritis. Adv Ther, 
2021. 38(1): p. 226-248. 
13. 
Lamba, M., et al., Extended-Release Once-Daily Formulation of Tofacitinib: Evaluation of Pharmacokinetics 
Compared With Immediate-Release Tofacitinib and Impact of Food. J Clin Pharmacol, 2016. 56(11): p. 1362-
1371. 
14. 
McInnes, I.B., et al., Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine 
signaling in human leukocyte subpopulations. Arthritis Res Ther, 2019. 21(1): p. 183. 
15. 
Furumoto, Y., et al., Tofacitinib Ameliorates Murine Lupus and Its Associated Vascular Dysfunction. Arthritis 
Rheumatol, 2017. 69(1): p. 148-160. 
16. 
Zhou, M., et al., JAK/STAT signaling controls the fate of CD8(+)CD103(+) tissue-resident memory T cell in lupus 
nephritis. J Autoimmun, 2020: p. 102424. 
17. 
Ikeda, K., et al., JAK inhibitor has the amelioration effect in lupus-prone mice: the involvement of IFN signature 
gene downregulation. BMC Immunol, 2017. 18(1): p. 41. 
18. 
You, H., et al., Successful treatment of arthritis and rash with tofacitinib in systemic lupus erythematosus: the 
experience from a single centre. Annals of the Rheumatic Diseases, 2019. 78(10): p. 1441-1443. 
19. 
ClinicalTrials.gov. Oral Tofacitinib in Adult Subjects With Discoid Lupus Erythematosus (DLE) and Systemic Lupus 
Erythematosus (SLE). Available from: https://clinicaltrials.gov/ct2/show/NCT03159936. 
20. 
XELJANZ and XELJANZ XR [package insert]. U.S. Pharmaceuticals Pfizer, Inc; 2021: New York, NY. . 
21. 
You, H., et al., Successful treatment of arthritis and rash with tofacitinib in systemic lupus erythematosus: the 
experience from a single centre. Ann Rheum Dis, 2019. 78(10): p. 1441-1443. 
22. 
Garufi, C., et al., Janus kinases inhibitors for treating patients with rhupus. Joint Bone Spine, 2020. 
23. 
Aringer, M., et al., 2019 European League Against Rheumatism/American College of Rheumatology Classification 
Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol, 2019. 71(9): p. 1400-1412. 
24. 
Albrecht, J., et al., The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome 
instrument for cutaneous lupus erythematosus. J Invest Dermatol, 2005. 125(5): p. 889-94. 


Autoimmunity Centers of Excellence 
Confidential 
Page 52 of 52 
ALE11 
Version 7.0 
October 25, 2023 
25. 
Fitzpatrick, T.B., The Validity and Practicality of Sun-Reactive Skin Types I Through VI. Arch Dermatol, 1988. 
124(6): p. 869-71. 
26. 
Sachdeva, S., Fitzpatrick skin typing: applications in dermatology. Indian J Dermatol Venereol Leprol, 2009. 75(1): 
p. 93-6. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ICF_002.pdf: 
National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
1
 
1. 
TITLE OF CLINICAL RESEARCH STUDY 
Evaluation of tofacitinib in prevention of photosensitivity in cutaneous lupus erythematosus 
(ALE11)  
 
2. 
PRINCIPAL INVESTIGATOR  
Principal Investigator:  
(Insert site PI information) 
 
The Principal Investigator is affiliated with the (Insert site PI affiliation).  
 
CONSENT SUMMARY/ KEY STUDY INFORMATION 
This consent contains information that will help you decide whether to take part in this 
research study. We encourage you to read the entire document. All the information is 
important, but here are some key points to help you understand the study. Additional 
information is available in the detailed consent section below.  
 
YOUR PARTICIPATION IS VOLUNTARY  
Your participation is voluntary. This study will be explained to you. You will have the 
opportunity to ask questions. Taking part in this study is your decision and will not affect your 
care if you decide not to participate. You may change your mind at any time while participating 
in the study. There will be no penalties or loss of benefits to which you are otherwise entitled if 
you do not want to take part in the study. 
 
Carefully review this informed consent form to ensure understanding of the study 
requirements. You will be given a copy of the signed consent for your records. 
 
Why is this research being done? 
The purpose of this clinical research study is to evaluate the impact of tofacitinib on ultraviolet 
(UV) light-induced skin inflammation in patients with cutaneous lupus erythematosus (CLE).  
CLE is an autoimmune disease which occurs when your immune system attacks and damages 
your healthy skin cells. Sunlight, a source of UV light, can make CLE worse. CLE can occur in 
patients with SLE but not all patients with CLE develop SLE.  
 
The study drug, tofacitinib (trade name XELJANZ® XR) is approved by the United States Food 
and Drug Administration (US FDA) for the treatment of rheumatoid arthritis (RA), psoriatic 
arthritis (PsA), ulcerative colitis (UC), and Polyarticular Course Juvenile Idiopathic Arthritis 
(pcJIA). It is not approved for the treatment of CLE or systemic lupus erythematosus (SLE). 
Therefore, the use of the study drug in this study is considered investigational.  
 
All participants of this study will undergo ultraviolet light exposure to a small area of skin before 
and after taking tofacitinib for about 25 days.  
 
 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
2
Is there any way being in this research can hurt me?  
The study drug has some risks associated with it. These include infections such as upper 
respiratory tract infection (nasopharyngitis, the common cold), lung infection, shingles, flu. 
More details about risks are in section 5 below (Risks and/or discomforts). 
 
 
Will being in this research study help me in any way? 
This study is designed to understand the biology of CLE and the effects of tofacitinib on the UV 
light induced CLE flares. It is not designed to provide you with any direct benefit. However, 
information learned from this study may benefit people with CLE and/or SLE in the future, see 
section 6 below (Potential benefits). 
 
What other choices do I have besides taking part in this research? 
You do not have to join this study to receive treatment for your CLE. You can continue to follow 
with your regular rheumatologist and discuss different treatment options, or you may volunteer 
for another study if you qualify. Before you decide to take part in this study, you may discuss 
the benefits and risks of available alternatives with the study doctor. See section 7 below 
(Alternatives to participation). 
 
DETAILED CONSENT INFORMATION 
 
3. INTRODUCTION AND BACKGROUND 
You are invited to take part in this research study (also known as a clinical trial) because your 
CLE makes your skin more sensitive to sunlight. This reaction is called photosensitivity and 
involves an unusually strong reaction to sunlight or other sources of ultraviolet (UV) rays. Some 
artificial sources of UV rays include indoor fluorescent lights, tanning beds, or black-light lamps.  
 
Exposure to UV rays is a common trigger for increased disease activity (flare) of both CLE and 
SLE. These flares can include rashes, fever, fatigue, joint pain, and other symptoms.  
 
The purpose of this clinical research study is to evaluate the impact of the study drug 
(tofacitinib) on UV light-induced skin inflammation in patients with CLE. Tofacitinib blocks the 
effect of inflammation, thus slowing the autoimmune process. In small trials and case reports, it 
is reported that tofacitinib is beneficial in treating CLE, however, its effects on photosensitivity 
have not been studied.  
 
 
4. STUDY COMPONENTS 
 
Who is sponsoring and conducting this study? 
The study is sponsored (funded and supported) by the National Institute of Allergy and 
Infectious Diseases (NIAID), of the National Institutes of Health (NIH). The Autoimmunity 
Centers of Excellence (ACE) are conducting the study.  
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
3
The Division of Allergy and Immunology (DAIT), a branch of NIAID will purchase the study drug. 
 
How long will I be in the study and how many people will be in the study? 
If you qualify for the study and decide to participate, your total length of time in the study, 
including the screening and treatment, will be about 8 weeks. This study will enroll 
approximately 10 people at 1-3 study sites in the United States.  
 
What am I being asked to do? 
If you choose to take part in this study, you will have to first sign this consent and complete the 
screening visit to see if you are eligible to participate.  
 
You will be required to do the following (see Table 1: Study Schedule): 
 Provide information on your overall health, CLE and SLE.   
 Provide blood samples four times during the study; we will take no more than 60 mL 
(about 12 teaspoons) at any one time 
 Have areas of your right buttock exposed to UV light on Day 0 and areas of your left 
buttock exposed to UV light on Day 25 
 Undergo three punch skin biopsies from the right buttock on Day 1 and three punch skin 
biopsies from the left buttock on Day 26 
 Take 11 mg of tofacitinib pills daily for 25 days, beginning on Day 2 
 
In Preparation for UVB Exposure and skin biopsies 
 Avoid tanning beds and sun exposure during the time of study participation 
 Do not use chemical sunscreens on the biopsy areas at least 12 hours prior to your UVB 
exposure appointment 
 After your biopsy, do not apply topical creams other than Vaseline to the biopsy site. 
 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
4
Table 1: Study Schedule 
 
Treatment phase 
 
Visit 
Screening 
1 
2 * 
3# 
4@ 
5$ 
6^ 
Early Termination 
Visit  
Unscheduled 
Visit 
Visit Days 
-30  
0 
1 
14 
25 
26 
40 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Demographics and Medical 
History 
X 
 
 
 
 
 
 
 
 
Medication assessment 
X 
X 
X 
X 
X 
X 
 
X 
X 
Eligibility Review 
X 
X 
 
 
 
 
 
 
 
EULAR/ACR Lupus diagnostic 
criteria 
X 
 
 
 
 
 
 
 
 
CLE and SLE disease activity 
assessments 
X 
X 
 
 
X 
 
 
X 
 
Fitzpatrick Skin Grading 
X 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
 
 
X 
 
 
X 
X 
Height, weight, vital signs 
X 
X 
X 
 
X 
X 
 
X 
X 
Adverse Event monitoring 
 
X 
X 
X 
X 
X 
X 
X 
X 
UVB Exposure 
 
X 
 
 
X 
 
 
 
 
Erythema Assessment 
 
 
X 
 
 
X 
 
 
 
Skin biopsy 
 
 
X 
 
 
X 
 
 
 
Stitch Removal 
 
 
 
X 
 
 
X 
 
 
Study Drug: tofacitinib 
(1 pill every morning)  
 
 
 
X** 
 
X 
 
 
X 
 
 
 
Pill count and diary review 
(Collect remaining product 
at end of participation) 
 
 
 
 
X 
 
 
X 
 
 
X 
 
Urine pregnancy 
 
 
 
 
X 
 
 
X 
 
Serum pregnancy 
X 
 
 
 
 
 
 
 
 
Clinical labs 
X 
 
 
 
X 
 
 
X 
X 
Research labs  
 
X 
 
 
X 
 
 
X 
 
 Volume for clinical labs (tsp) 
4 
0 
0 
0 
4 
0 
0 
4 
4 
 Volume for research labs 
(tsp) at University of 
Michigan 
0 
10 
0 
0 
10 
0 
0 
0 
0 
Volume for research labs 
(tsp) if not at University of 
Michigan 
0 
4 
0 
0 
4 
0 
0 
0 
0 
Total visit draw volume (tsp) 
at University of Michigan 
4 
10 
0 
0 
14 
0 
0 
4 
4 
Total visit draw volume (tsp) 
if not at University of 
Michigan 
4 
4 
0 
0 
8 
0 
0 
4 
4 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
5
Visit Windows
*Visit 2-20-28hrs after first UVB exposure 
# Visit 3- Day 10-15 
@ Visit 4- Day 21-29 
$ Visit 5- 20-28 hrs. after 2nd UVB exposure 
^ Visit 6- Day 36-41 
**First dose of study drug -Take on day 2 
 
Screening Visit 
At the Screening Visit the following will occur to determine if you are eligible to be in the study: 
1. A complete medical history, demographic information, for example, age, gender and all 
your current medications that you are taking will be written down in the research 
record. 
2. Other medical records such as imaging results, laboratory work, and other tests done as 
part of clinical care may be accessed for future research data purposes. 
3. If you are a female of childbearing age, a pregnancy test will be done using a blood 
sample.  
4. A sample of your blood will be collected for laboratory tests. 
5. The study doctor will assess your skin involvement.  
6. You will have a physical examination, including measurement of your weight and height. 
 
Day 0 
Once you are deemed eligible for the study, you will return for the Day 0 visit. At this visit, you 
will have a physical exam and blood samples taken. You will have eight small areas (¾” x ¾”) of 
your right buttock exposed to ultraviolet light. UV light exposure is roughly similar to 15-30 
minutes of summer sun exposure. The amount of UV is intended to include a dose that will 
cause mild redness.  
 
Day 1 
On Day 1, you will return to clinic to have the site of UV exposure assessed for redness and you 
will undergo 3 skin biopsies taken from your right buttock and a single stich placed at each site 
(each biopsy is the size of the end of a pencil eraser).   
 
You will then be given tofacitinib 11 mg to take daily over the next 4 weeks. We will provide you 
with a diary to help you track your pill intake and ask that you record your daily intake including 
missed doses.  
 
You will swallow the tofacitinib tablets every morning with or without food, whole and intact, 
do not crush, split, or chew. When you take this type of tofacitinib tablet, you may see 
something in your stool that looks like a tablet, this is from the medicine being absorbed into 
your body and leaving the tablet outer coating intact, which is normal.  
 
 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
6
Day 14 
On Day 14 you will return to the study site with the bottle of tofacitinib and the pill diary for 
review. You will have your stitches removed and to monitor for adverse events at this visit.  
 
Day 25 
On Day 25, you will return with your bottle of tofacitinib and the pill diary. You will have a 
physical exam, and blood and urine samples taken. You will have small areas of your left 
buttock exposed to ultraviolet light. The doses of UV light are intended to include a dose that 
will be enough to cause some redness in most participants.  
 
Day 26  
On Day 26, you will return with your bottle of tofacitinib and diary to clinic to have the site of 
UV exposure assessed for redness, and you will undergo 3 skin biopsies taken from your left 
buttock. 
 
Day 40 
On Day 40 you will return to have the stitches removed and to monitor for adverse events. 
 
During the study, you will be able to continue to take certain medications, including oral 
corticosteroids (e.g., prednisone), hydroxychloroquine, quinacrine, methotrexate, leflunomide 
and mycophenolate mofetil (MMF). You will need to be on a stable dose of those medications 
for the last 4 weeks when you enter the study. If you are taking NSAIDs you should be on the 
same daily dose for at least the 1 week just prior to when you enter the study.  
 
Use of tofacitinib in combination with biologic disease-modifying antirheumatic drugs 
(DMARDs) or potent immunosuppressants such as azathioprine and cyclosporine is not allowed.  
 
You cannot receive any live or attenuated vaccines within 6 weeks prior to Visit 1 (Day 0) and 
throughout the study. You can receive non-live vaccines at least 2 weeks prior to initiating study 
drug. 
 
It is recommended that you do not receive any type of vaccine for at least a month after you 
stop taking tofacitinib. 
 
5. RISKS and/or DISCOMFORTS 
For your safety, you must tell the study staff about all medications you are taking before you 
start the study, and any changes in your medications while in the study. There may be unknown 
or unforeseeable risks to participation in the study. It is important that you report any and all 
symptoms or possible reactions to your study doctor, even if you think it isn’t related to your 
study participation. 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following side effects of tofacitinib have been observed in clinical trials: 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
7
 
Infections 
Tofacitinib is a medicine that affects your immune system. Tofacitinib can lower the ability of 
your immune system to fight infections. Some people have serious infections while taking oral 
tofacitinib, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that 
can spread throughout the body. Some people have died from these infections. You should not 
start taking tofacitinib if you have any kind of infection. People who are older than 65 years of 
age, people with diabetes, and people with chronic lung disease may have a higher risk of 
infection. 
 
We strongly advise you to stay up to date with all current CDC vaccine recommendations. 
 
We recommend that you be up to date with COVID-19 vaccinations per current CDC 
recommendations. If the CDC recommends a medication to prevent COVID-19 infection that 
may be an option. 
 
Risk of chronic herpes infection: 
Tofacitinib may increase your risk of outbreaks of herpes zoster (shingles) or other herpes 
infections (“cold sores” or “fever blisters” or ulcer involving the lips, mouth, or genital area). It 
is important for people who have chronic oral or genital herpes to be aware of this risk. If you 
or your sex partner have been diagnosed with oral or genital herpes, we recommend that you 
take your medicine as prescribed. If you have open sores, do not touch the fluids from herpes 
sores to avoid spreading it. Always use a physical barrier, (e.g., condoms) during sex to decrease 
the chance of getting herpes or infecting a sex partner. 
 
If you develop an infection during your participation in the study, we will ask you to stop 
taking the study medication until you have recovered from the infection. We will ask that 
you return for a safety follow-up after you have recovered. You may be asked to restart a 
25-day dose of study medication after you have fully recovered from the infection.  
 
After starting tofacitinib, call your study doctor right away if you have any symptoms of any 
infection.  
 
Cancer and immune system problems 
Tofacitinib may increase your risk of certain cancers by changing the way your immune system 
works. Your risk of some skin cancers may be increased with tofacitinib. Your skin may be 
examined periodically by your doctor. Lymphoma and other cancers can happen in patients 
taking tofacitinib. Some of the other cancers that have happened include lung cancer, breast 
cancer, melanoma, prostate cancer, and pancreatic cancer. Some people who have taken oral 
tofacitinib with certain other medicines to prevent kidney transplant rejection have had a 
problem with certain white blood cells growing out of control (Epstein Barr Virus-associated 
post-transplant lymphoproliferative disorder). Tell your study doctor if you have ever had any 
type of cancer or if you are diagnosed with any type of cancer during the study. 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
8
Risk of heart related issues: 
Taking tofacitinib may increase your risk of heart related issues such as heart attack or stroke, 
blood clots and death. 
Let your study doctor know if you are a current or past smoker, or have had a heart attack, 
other heart problems, stroke or blood clots in the past as these may put you at higher risk for 
serious problems while taking tofacitinib. 
 
Here are the symptoms to watch for while taking tofacitinib:  
Heart attack 
Someone having a heart attack may experience several symptoms including: 
 Chest pain or discomfort that doesn’t go away after a few minutes. 
 Pain or discomfort in the jaw, neck, or back. 
 Weakness, light-headedness, nausea (feeling sick to your stomach), or a cold sweat. 
 Pain or discomfort in the arms or shoulder. 
 Shortness of breath. 
 
Stroke 
Someone having a stroke may experience several symptoms including:  
 Sudden numbness or weakness, especially on one side of the body 
 Sudden confusion or trouble speaking or understanding speech 
 Sudden trouble seeing in one or both eyes 
 Sudden trouble with walking, dizziness, or loss of balance or coordination 
 Sudden severe headache with no known cause 
 
If you think that you may be having a heart attack or stroke, call 9-1-1 immediately. 
 
Blood clot 
Someone with a blood clot may experience any one of the following symptoms in an arm or leg: 
 Swelling 
 Pain or tenderness not caused by injury 
 Skin that is red, discolored or warm to the touch 
 
If you think you may have a blood clot you should seek immediate medical care. 
 
 
 
 
 
 
 
 
 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
9
Table 2: Frequency of adverse events 
 
 
Tears or holes (perforation) in the stomach or intestines  
Tell your study doctor if you have had diverticulitis (inflammation of outpouchings in parts of 
the large intestine) or ulcers in your stomach or intestines. Some people taking oral tofacitinib 
get tears or holes in their stomach or intestine.  
 
Tell your study doctor right away if you have fever and stomach-area pain that does not go 
away, and a change in your bowel habits.  
 
Blockage of the stomach or intestines 
Tell your study doctor if you have narrowing of the stomach or intestine, e.g., a stricture. The 
form of tofacitinib (XELJANZ® XR) being used in the study may cause a blockage or obstruction 
at the site of narrowing in your stomach or intestine. 
 
Changes in certain laboratory test results 
Your study doctor will test your blood before you start receiving tofacitinib and when you finish 
tofacitinib (day 25). Some changes in blood tests that can occur with tofacitinib include:  
Very common (may affect > 1 in 10 people) 
Upper respiratory tract infection (nasopharyngitis, common cold) 
Common (may affect up to 1 in 10 people) 
Lung infection (pneumonia, bronchitis) 
Shingles (herpes zoster) 
Influenza (flu) 
Sinus infection  
Urinary or bladder infection (cystitis)  
Sore throat (pharyngitis) 
Increased liver enzymes, muscle enzymes 
or cholesterol  
Weight gain
Stomach (belly) pain (may be from 
inflammation of the stomach lining) 
Vomiting, diarrhea, nausea, indigestion
Pain in the muscles and joints  
Low white blood cell count  
Low red blood cell count (anemia)  
Fever  
Fatigue (tiredness)  
Swelling of the feet and hands 
Headache  
High blood pressure (hypertension) 
Poor sleep  
Shortness of breath, difficulty 
breathing  
Cough  
Rash  
Itching 
Uncommon (may affect up to 1 in 100 people) 
Blood infection (sepsis) 
Tuberculosis 
Kidney infection  
Skin infection  
Herpes simplex or cold sores (oral herpes) 
Blood creatinine increased (a possible 
sign of decreased kidney function)  
Dehydration 
Heart attack*
Muscle strain  
Tendonitis  
Joint swelling  
Joint infection  
Ligament sprain  
Abnormal sensations  
Sinus congestion 
Skin redness 
Blood clots*
Fatty liver  
Inflammation of outpouchings of 
your intestine (diverticulitis)  
Tears in your stomach or 
intestines  
Viral infections  
Some types of skin cancers 
(nonmelanoma-types) 
Stroke*
Rare (may affect up to 1 in 1,000 people) 
Tuberculosis involving the brain and 
spinal cord, bones, and other organs
Other unusual infections 
 
*Current or past smoker, and those with a history of heart attack, heart problems, stroke or blood clots may be at a
higher risk


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
10
 Decrease in white cell counts (white blood cells fight off infections) 
 Decrease in red blood cell count (low red cell counts may cause anemia and make you feel 
weak and tired) 
 Increase in certain liver tests 
 Increase in cholesterol level 
 Increase in muscle enzymes tests 
 Change in tests related to kidney function 
 
The study doctor will discuss any abnormal lab test results with you. 
 
Risks of Ultraviolet Light Exposure 
Part of this study includes a brief exposure to different doses of ultraviolet light. The areas 
exposed are small (about 1 cm2 or ¾” x ¾” each), but there is a risk of some burning sensation 
in the areas exposed. In addition, the ultraviolet light exposure could cause a rash. If your skin 
reacts to sunlight, it will likely react similarly in the areas we test. In individuals without CLE 
and/or SLE this might include turning pink or developing a tan which usually fades within a few 
weeks.  
 
Risks of Punch Biopsies 
The local anesthesia used to numb the area can produce a stinging sensation that lasts for a few 
seconds prior to the procedure. You may experience minimal pain or bleeding after the 
procedure. There may also be a small scar visible after the biopsy sites heal. The procedure is 
performed by a specially trained and highly experienced physician, nurse, or physician’s 
assistant. You will have a suture placed at each biopsy site and study personnel will provide 
care instructions and a time to return to have the sutures removed.  
 
Risks of Blood Draws 
Drawing blood from a vein in your arm may cause some discomfort, bleeding, or bruising, and 
rarely, infection at puncture site or fainting. A total of 120mL (about 24 teaspoons) of blood will 
be collected over the course of the entire study. Blood will be drawn by trained persons and 
sterile technique will be used to minimize the risk of infection. 
 
Risks Associated with Stored and Shared Blood and Information: 
For this project, we will collect, store, and use blood and biopsied tissue samples and health 
information for research. The information will be stored on a password protected computer 
shared drive. The only people that will have access to these are the principal investigator, Dr. 
Kahlenberg, and approved study team members. Details of how your identity will be protected 
to the extent permitted by law will be described later in this form. Also, at the end of this form 
you will be asked to consider allowing storage of samples for future use which may not be 
directly related to this study.  
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
11
The Confidentiality Section later in this form describes the safeguards used to code information 
that could link results back to you. Every effort will be made to protect your privacy to the 
extent permitted by law.  
 
Additional Risks 
As with any research study, there may be additional risks that are unknown or unexpected. 
 
6. POTENTIAL BENEFITS 
If you agree to take part in this study, there is no expected medical benefit to you. Information 
learned from this study may someday benefit people with CLE and/or SLE. We may learn 
information about your health as part of research. We will share this information with you.  
 
7. ALTERNATIVES TO PARTICIPATION  
You may choose not to be in this research study. There may be other research studies that you 
can choose to join if you qualify. 
 
You do not have to join this study to receive treatment for your CLE and/or SLE. You can 
continue to follow with your regular rheumatologist and discuss different treatment options, or 
you may volunteer for another study if you qualify instead of volunteering for this study. Before 
you decide to take part in this study, you may discuss the benefits and risks or available 
alternatives with the study doctor. 
 
8. NEW FINDINGS 
During your participation in this study, your study doctor will inform you of any new findings 
from this or other research that may affect your willingness to continue in this study. If new 
information is provided to you after you have joined the study, it is possible that you may be 
asked to sign a new consent form that includes the new information. 
 
9. VOLUNTARY WITHDRAWAL FROM STUDY 
You may decide not to take part or to leave the study at any time. If you decide to leave the study, 
there is no penalty or loss of benefits in your routine medical care or any other benefit(s) that 
you would otherwise be entitled to receive. In addition, you should talk to your study doctor who 
will discuss future treatment and procedures for your continued care.  
 
10. REASONS WHY YOU MAY BE TAKEN OFF STUDY WITHOUT YOUR CONSENT 
You may be removed from the study without your consent at any time. Reasons why you may 
be removed from the study include, but are not limited to, the following: 
 Your study doctor determines that it is in your best interest not to take part 
 You are unable to complete required study treatments and examinations 
 You become ineligible to participate 
 Your condition changes and you need treatment that is not allowed while you are taking 
part in the study 
 You do not follow instructions from the researchers 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
12
 The study is stopped by the Institution, the sponsor, or other health authorities 
 
If you are removed from the study your study doctor will notify you about treatment or 
procedures for your continued care. 
 
 
11. PREGNANCIES, BREASTFEEDING AND BIRTH CONTROL 
Tofacitinib may affect the ability of females to get pregnant. If you are female of childbearing 
potential, a pregnancy test will be performed prior to your enrollment and on day 25 of this 
study.  If you are a male or female who engages in sexual activity that could lead to pregnancy, 
you must agree to use complete abstinence or an FDA-regulated contraception for the duration 
of the study and for one month after stopping the study drug to prevent pregnancy. Periodic 
abstinence and withdrawal are not acceptable methods of contraception.  
 
Acceptable forms of birth control include: 
 
 Oral birth control pills (combined hormone or progestin alone) 
 Injectable or implantable progestogens 
 Intrauterine devices or estrogen vaginal rings 
 Double barrier methods (e.g., condom and occlusive cap with spermicidal agent)  
 Tubal ligation-both sides 
 Male sterilization (This must be a female participant’s only partner) 
 
You should not take tofacitinib if: 
 You are pregnant 
 You are breastfeeding 
 Are unable or unwilling to use an effective form of birth control (see below) 
 
Treatments and procedures involved in this research project may involve unexpected risks to 
your unborn.  
 
If you are a female participant who becomes pregnant or if you are a male participant whose 
female partner become pregnant during the study, you must notify your study doctor 
immediately.  
 
For female participants who become pregnant during the treatment, the study drug will be 
discontinued.  
 
For male and female participants, we will continue to follow you until the baby is born or the 
pregnancy stops. Your study team will ask you about the length of the pregnancy, whether it is 
ongoing, whether a baby was born and the health of the baby. 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
13
12. COSTS TO THE PARTICIPANT (YOU) 
You will not be charged while you are participating in this study. Also, all procedures that are 
required for this study, and are not part of your regular medical care, will be provided to you at 
no charge. Any costs related to usual clinical care of your CLE and/or SLE or other medical 
problems will be billed to you and/or your insurance provider(s). 
 
Ask your study doctor about any expected added costs that may result from your participation 
in this study. Insurance companies and other carriers sometimes refuse to pay the costs of 
treatment when individuals are participating in research. Check with your health plan or 
insurance company to find out what they will pay for. Taking part in this study may lead to 
added costs for you or your insurance company. There will be no charge to you or your health 
insurance company for any costs which are directly related to this study. 
 
13. REIMBURSEMENT 
You will be paid (XX) for each study visit. Compensation will be considered for travel, hotel 
accommodations, etc., as needed. In addition, if you travel more than 50 miles away, you will 
be offered compensation for mileage based on Internal Revenue Service (IRS) regulations. 
There will be no financial charge for the medication. 
 
If you receive payment of (XX) for taking part in this study, (insert institution name here) 
accounting department will collect your name, address, social security number, payment 
amount, and related information. The information collected will be used for tax reporting 
purposes if you participate in additional studies and the total amount of study payment 
exceeds $600 in a calendar year. In this situation (insert your institution name here) accounting 
department is required for tax reporting purposes to submit this information to the IRS. 
 
14. RESEARCH-RELATED INJURY 
If you are injured or get sick while in this study, it is important to tell your study doctor. 
If you should be injured or become ill as a result of your participation in this study, emergency 
medical care is available to you, but you or your insurance company will be charged for this 
treatment. The hospitals and/or treating physicians reserve the right to bill you and/or your 
insurance provider(s) for services you receive for the injury. No payment or additional 
compensation is available to you as a result of such injuries or illnesses. There is no provision 
for free medical care or monetary compensation from the study sponsor, the NIAID, NIH. You 
do not lose any legal rights by signing this form. 
 
15. CONFIDENTIALITY  
Your medical and research records will be confidential to the extent permitted by law. Every 
effort is made to keep your identity private. However, we cannot always guarantee complete 
confidentiality. 
 
You will be identified by a study code, not your name. The key to the code is kept in a secured 
electronic file where only <Insert PI name> and other designated study personnel will have 
access. Personal data from your records will not be released without your written permission. 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
14
You will not be named in any publication about this study. Any paper documents will be kept in 
a locked room during the study with access only to Dr. Kahlenberg and other designated study 
personnel. 
 
After the study is completed, the study data may be placed in a central storage location. The 
purpose is to make study data available to other researchers who must request permission 
from NIAID/NIH. This data does not include names of any of the participants and your privacy is 
protected whenever this data is used. As an NIH funded study, you are further protected 
through a policy that prevents the investigator from disclosing sensitive study information that 
would lead to your identity. This does not prevent you or a family member from voluntarily 
releasing information about yourself or your involvement in this research. 
 
Medical and research records from this study will be reviewed by the United States agency 
funding this study (the National Institute of Allergy and Infectious Diseases), including its, 
representatives, agents, employees, contractors, and other persons assisting in conducting, 
monitoring, or analyzing the study.  
 
A description of this clinical trial (NCT #05048238) is available on http://www.ClinicalTrials.gov, 
as required by U.S. law. This website will not include information that can identify you. At most, 
the website will include a summary of the results. You can search this website at any time. 
 
Organizations that may look at and/or copy your medical records for research, quality 
assurance and data analysis include: 
 The National Institute of Allergy and Infectious Diseases, (NIAID) sponsor of the 
research 
 NIAID representatives, agents, employees, contractors, and other persons assisting in 
conducting, monitoring, or analyzing the study 
 The U.S. Food and Drug Administration 
 State and other health authorities 
 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
15
16. PROBLEMS OR QUESTIONS  
If you have questions about this study, you should contact the researchers listed below to: 
 Obtain more information about the study 
 Ask a question about the study procedures or treatments 
 Talk about study-related costs to you or your health plan  
 Report an illness, injury, or other problem (you may also need to tell your regular 
doctors) 
 Leave the study before it is finished 
 Express a concern about the study 
 
Principal Investigator: 
Insert Site PI 
Mailing Address: 
Insert site address 
Telephone: 
Insert site phone number 
 
Study Coordinator:  
 
Insert site coordinator 
Mailing Address:  
 
Insert site coordinator address 
Telephone:  
 
Insert site coordinator phone number 
 
You may also express a concern about a study by contacting the Institutional Review Board 
listed below. 
 
University of Michigan Medical School Institutional Review Board (IRBMED) 
2800 Plymouth Road 
Building 520, Room 3214 
Ann Arbor, MI 48109-2800 
Telephone: 734-763-4768 (For International Studies: US Country Code: 001) 
Fax: 734-763-1234 
e-mail: irbmed@umich.edu  
 
If you are concerned about a possible violation of your privacy or concerned about a study, you 
may contact the (Insert site contact information) 
 
When you call or write about a concern, please provide as much information as possible, 
including the name of the researcher, the IRBMED number (at the top of this form), and details 
about the problem. This will help University officials to look into your concern. When reporting 
a concern, you do not have to give your name unless you want to. 
 
17. FUTURE USE OF DATA/BIOLOGICAL SAMPLES 
Stored Samples and Information: 
Information about you, including your biospecimens and other data, collected for this study 
may be shared with other researchers. It may also be used for other research studies. This 
information will be coded so that other investigators will not have access to your personal 
information. We will not ask you for additional permission before sharing the information.  


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
16
 
Your samples/data may be shared with other researchers; this data would be coded so that 
other investigators would not have access to your personal information.   
 
We are asking additional permission to store leftover samples of blood and biopsy tissue that 
are collected during your participation in study to be used for research and sharing with other 
investigators in the future for tests that aren’t yet planned. These tests will be related to the 
study of CLE, the response to medication, autoimmune disease, and the immune response. 
The tests may include genetic tests to study large chunks of your DNA (whole exome testing) 
or all of your DNA at once (whole genome testing). 
 
The results of tests performed on stored samples or reports resulting from the analysis of your 
samples: 
 will not be given to you or a doctor who is not an investigator in this study 
 will not be put in your medical record 
 will not identify you 
 will not affect your routine medical care 
 
There is no benefit to you from the storage and sharing of samples and the information learned 
from the research using them. However, the use of your samples and information may help 
researchers learn more about your disease. The purpose of storage and sharing data is to make 
information available for use in health research. Collecting, storing, sharing information, and 
making it available for other studies may help people in the future. 
 
Samples will be stored at the University of Michigan. If you decide to allow storage, your 
samples and information may be stored for an unknown length of time. Any research 
conducted using your stored samples will be reviewed and approved by an Institutional Review 
Board (IRB). This board evaluates the science, integrity and ethics of clinical research involving 
human subjects.  
 
Although your stored samples will not be sold, information obtained from the samples may in 
the future lead to the development of commercial products. You will not receive any money 
from research using your stored samples and information. 
 
Researchers are required to protect your privacy and to keep your information private to the 
extent permitted by law. There may be risks in allowing the storage or analysis of samples and 
information. Your samples will be coded with a number so that you cannot be identified. Only 
your study doctor will have the code that links your identity to your specimens. Although we 
remove personal identifiers, we cannot guarantee complete confidentiality. For example, 
because genetic information is unique to you there is a risk that someone using your samples 
for genetic studies could trace the sample back to you or to those related to you.  
 
You can change your mind at any time during the study and ask to have your samples 
destroyed. This request should be made in writing to the study doctor. If your samples have not 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
17
been used, they will be destroyed. If your samples have already been tested before your 
request is received, the information from these tests will be used and cannot be destroyed.  
 
Your decision regarding the storage and sharing of samples for future research that is not part 
of this study and the information (data) resulting from the analysis of your samples will not 
affect your routine medical care or your ability to participate in this clinical trial. The future use 
of your samples and information may contribute to learning more about disease or help to 
study the genetics related to a specific condition.  
 
 
 
 
 
 
 
 
 
 
 
Please sign below if you agree to take part in this study. 
 you have read the informed consent and/or had it explained to you 
 you were given the opportunity to ask questions about the information, and 
 you voluntarily agree to take part in the study 
 
Consent/Assent to Collect for Unspecified Future Research  
This project involves the option to allow the study team to keep your collected specimens/data for 
use in future research. I understand that it is my choice whether or not to allow future use of my 
specimens. I understand that if my ability to consent or assent for myself changes, either I or my 
legal representative may be asked to re-consent prior to my continued participation in this study. 
 
_____ Yes, I agree to let the study team keep my specimens for future research. 
 
_____ No, I do not agree to let the study team keep my specimens for future research. 
 
 
Print Legal Name: ___________________________________________________________________ 
 
 
Signature: ______________________________     Date (mm/dd/yyyy):_______________________ 


National Institute of Allergy and Infectious Diseases (NIAID) 
Division of Allergy, Immunology and Transplantation (DAIT) 
Sponsor Informed Consent Form Template  
Protocol ALE11 ICF NCT#05048238 
 
Version 8.0 
Date: October 25,2023 
 
                                        
                                    
 
 
 
18
 
  
 
(NOTE: This consent form with the original signatures MUST be retained on file by the 
principal investigator. A copy must be given to the research subject. A copy should be placed 
in the research subject’s medical record, if applicable.) 
Consent/Assent to Participate in the Research Study 
 
I understand the information printed on this form. I have discussed this study, its risks and potential 
benefits, and my other choices with [NAME OF STUDY TEAM MEMBER OBTAINING CONSENT] 
______________________. My questions so far have been answered. I understand that if I have 
more questions or concerns about the study or my participation as a research subject, I may contact 
one of the people listed in Section 16 (above). I understand that I will receive a copy of this form at 
the time I sign it and later upon request. I understand that if my ability to consent or assent for 
myself changes, either I or my legal representative may be asked to re-consent prior to my continued 
participation in this study. 
 
 
Print Legal Name: ___________________________________________________________________ 
 
 
 
Signature: ________________________     Date (mm/dd/yyyy): ___________________________ 
 
 
Signature of investigator or designated person explaining and obtaining the consent 
 
 
__________________________       ___________________________ 
 
_______________ 
Name and Title  
                    Signature 
 
 
 
        Date (mm/dd/yyyy) 
(Typed or printed)