Utilization of a Cutaneous Therapy In Situ Microdevice
Phase: PHASE4
Conditions: Psoriasis, Atopic Dermatitis
Sponsor: University of California, San Francisco

Raymond Cho, MD, PhD 
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Clinical Research Protocol 
Utilization of a cutaneous therapy in situ microdevice  
Protocol Number: 
 
Version Date: 
11/11/25  
Investigational Product: 
Utilization of a cutaneous therapy in situ microdevice 
IND Number: 
 
Development Phase: 
 
Sponsor: 
Raymond Cho 
Department of Dermatology 
1701 Divisadero St. 4th Floor 
San Francisco, CA 94143 
Funding Organization: 
 
Principal Investigator: 
Raymond Cho  
Telephone: (650)520-0208 
 
E-mail: Raymond.cho@ucsf.edu 
 
 
Approval: 
 
 
 
 
 
 
PI or Sponsor Signature (Name and Title)  
 
 
Date 
 
 

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This confidential information about an investigational product is provided for the exclusive use of 
investigators of this product and is subject to recall at any time.  The information in this document 
may not be disclosed unless federal or state law or regulations require such disclosure.  Subject to the 
foregoing, this information may be disclosed only to those persons involved in the study who have a 
need to know, with the obligation not to further disseminate this information.   
 
 
 
 
 
 
 
 

Raymond Cho, MD, PhD 
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PROTOCOL AGREEMENT 
 
I have read the protocol specified below. In my formal capacity as Investigator, my duties 
include ensuring the safety of the study subjects enrolled under my supervision and 
providing Raymond Cho with complete and timely information, as outlined in the 
protocol.  It is understood that all information pertaining to the study will be held strictly 
confidential and that this confidentiality requirement applies to all study staff at this site. 
Furthermore, on behalf of the study staff and myself, I agree to maintain the procedures 
required to carry out the study in accordance with accepted GCP principles and to abide 
by the terms of this protocol. 
 
Protocol Number:   
 
Protocol Title: MICRODEVICE-BASED CUTANEOUS THERAPY OPTIMIZATION 
 
Protocol Date:  11/11/25 
 
 
 
 
Investigator Signature  
 
Date 
 
Print Name and Title 
Site # 
 
 
Site Name 
 
Address 
 
 
 
 
 
 
 
 
 
Phone Number 
 

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TABLE OF CONTENTS 
 
1 
BACKGROUND .................................................................................................................. 9 
       1.1    Overview of Non-Clinical Studies ............................................................................... 10 
1.2 
Overview of Clinical Studies ....................................................................................... 10 
2 
STUDY RATIONALE ........................................................................................................ 10 
2.1 
Risk / Benefit Assessment ........................................................................................... 11 
3 
STUDY OBJECTIVES ....................................................................................................... 11 
3.1 
Primary Objective ........................................................................................................ 11 
3.2 
Secondary Objectives .................................................................................................. 11 
4 
STUDY DESIGN ................................................................................................................. 11 
4.1 
Study Overview ........................................................................................................... 11 
5 
CRITERIA FOR EVALUATION ...................................................................................... 12 
5.1 
Primary Efficacy Endpoint .......................................................................................... 14 
5.2 
Secondary Efficacy Endpoints ..................................................................................... 14 
5.3 
Safety Evaluations ....................................................................................................... 14 
6 
SUBJECT SELECTION ..................................................................................................... 15 
6.1 
Study Population .......................................................................................................... 15 
6.2 
Inclusion Criteria ......................................................................................................... 15 
6.3 
Exclusion Criteria ........................................................................................................ 15 
7 
CONCURRENT MEDICATIONS .................................................................................... 15 
7.1 
Allowed ........................................................................................................................ 15 
7.2 
Prohibited ..................................................................................................................... 15 
8 
STUDY TREATMENTS ..................................................................................................... 16 
8.1 
Method of Assigning Subjects to Treatment Groups .................................................. 16 
8.2 
Blinding ....................................................................................................................... 16 
8.3 
Test and Control Formulation ...................................................................................... 16 
8.4 
Supply of Study Medication at the Site ....................................................................... 16 
8.5 
Study Medication Accountability ................................................................................ 17 
9 
STUDY PROCEDURES AND GUIDELINES ................................................................. 17 
9.1 
Clinical Assessments ................................................................................................... 17 
10 EVALUATIONS BY VISIT ............................................................................................... 18 
10.1 Visit 1 (Screening Visit and Device Placement) ......................................................... 18 
10.2 Visit 2 (Device Retrieval Visit) ................................................................................... 18 
11 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ........................ 19 
11.1 Adverse Events ............................................................................................................ 19 
11.2 Serious Adverse Experiences (SAE) ........................................................................... 18 
11.3 Medical Monitoring ..................................................................................................... 18 
12 DISCONTINUATION AND REPLACEMENT OF SUBJECTS ................................... 19 
12.1 Early Discontinuation of Study Device ....................................................................... 19 

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12.2 Withdrawal of Subjects ................................................................................................ 19 
12.3 Replacement of Subjects .............................................................................................. 19 
13 PROTOCOL VIOLATIONS .............................................................................................. 19 
14 STATISTICAL METHODS AND CONSIDERATIONS ................................................ 22 
14.1 Data Sets Analyzed ...................................................................................................... 22 
14.2 Demographic and Baseline Characteristics ................................................................. 22 
14.3 Analysis of Primary Endpoint ..................................................................................... 22 
14.4 Analysis of Secondary Endpoints ................................................................................ 22 
14.5 Sample Size and Randomization ................................................................................. 23 
15 DATA COLLECTION, RETENTION AND MONITORING ....................................... 23 
15.1 Data Collection Instruments ........................................................................................ 23 
15.2 Data Management Procedures ..................................................................................... 23 
15.3 Availability and Retention of Investigational Records ................................................ 23 
15.4   Subject Confidentiality……………………………………………………………….23 
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS ................... 24 
16.1 Protocol Amendments ................................................................................................. 24 
16.2 Institutional Review Boards and Independent Ethics Committees .............................. 24 
16.3 Informed Consent Form ............................................................................................... 25 
16.4 Publications .................................................................................................................. 25 
16.5 Investigator Responsibilities ........................................................................................ 26 
 
 

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LIST OF ABBREVIATIONS 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IF 
Immunofluorescence 
IHC 
Immunohistochemistry 
IRB 
Institutional Review Board 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
SAE 
Serious Adverse Experience 

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PROTOCOL SYNOPSIS 
TITLE 
MICRODEVICE-BASED CUTANEOUS THERAPY 
OPTIMIZATION 
SPONSOR 
Raymond Cho 
FUNDING 
ORGANIZATION 
None 
NUMBER OF SITES 
1 
RATIONALE 
This study will aim to establish the feasibility of clinical application 
of an in situ candidate drug screening microdevice in atopic dermatitis 
and psoriasis, and the ability of the device to predict response to FDA-
approved standard of care skin disease treatments. We will also 
investigate preliminary correlations between drug response as 
assessed by the microdevice and molecular features of the treated 
rashes.  
STUDY DESIGN 
This is a pilot study aimed at determining the feasibility of using an in 
situ microdevice to measure local improvement in cutaneous 
inflammation to different FDA approved skin therapies.  
PRIMARY 
OBJECTIVE 
The primary objectives are to evaluate the safety of microdevice 
placement and removal based on assessment of adverse events, and to 
determine the feasibility of microdevice analysis based on the ability 
to place and retrieve the device with sufficient tissue, of sufficient 
quality, for downstream histopathology/molecular analysis and 
interpretation of at least 80% of the device reservoirs.  
SECONDARY 
OBJECTIVES 
The secondary objectives are to test feasibility of utilizing quantitative 
histopathologic assessment and/or transcriptional profiling to 
determine whether there is local improvement in lesional rash-affected 
skin with clinically relevant skin inflammation treating agents.   
NUMBER OF 
SUBJECTS 
20 patients 
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria: > 18 years of age, patients with atopic dermatitis or 
psoriasis; if female patient with child bearing potential (on oral 
contraceptive pills or intrauterine device for at least 30 days) 
Exclusion Criteria: None 
 
TEST PRODUCT, 
DOSE, AND ROUTE 
OF 
ADMINISTRATION 
After placement, the microdevice will dwell in lesional inflamed skin 
for approximately 72 +/- 24 hours, enabling micro-doses of drugs to 
be released from the reservoirs and elicit local responses.  

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CONTROL 
PRODUCT, DOSE 
AND ROUTE OF 
ADMINISTRATION 
The in situ microdevice will contain a subset of the following FDA 
approved medications: Triamcinolone, 5-fluorouracil, Calcipotriene, 
Tapinarof, Crisaborole, Tacrolimus, Adalimumab, Etanercept, 
Certolizumab, Infliximab, Secukinumab, Ixekizumab, Apremilast, 
Risankizumab, Ustekinumab, Hydroxychloroquine, Methotrexate, 
Mycophenolate, Azathioprine, Chloroquine, Cyclosporine, 
Tofacitinib, Deucravacitinib, Dupilumab, Tralokinumab, 
Guselkumab, Tildrakizumab, Baractinib, Abrocitinib, Upadacitinib, 
Lebrikizumab, Nemolizumab, Ruxolitinib, Bimekizumab, 
Roflumilast. 
DURATION OF 
SUBJECT 
PARTICIPATION 
AND DURATION OF 
STUDY 
The study will last ~3 days.  The device is placed on day 0 and left in 
place for ~ 72 hours.  If logistical issues arise, it is acceptable (i.e. not 
a deviation) for the device to be removed up to 104 hours after 
placement and still be evaluated for the research protocol. Please note 
that the biomaterials of the microdevice are acceptable from a safety 
standpoint for long-term dwelling in tissue. 
CONCOMMITANT 
MEDICATIONS 
Allowed: all 
Prohibited: none 
EFFICACY 
EVALUATIONS 
 
PRIMARY ENDPOINT 
The primary endpoint is the evaluation of the safety and feasibility of 
the microdevice, specifically assessing adverse events associated with 
device placement and removal. This endpoint is appropriate as it 
directly addresses the study's primary objective of evaluating the 
safety of microdevice placement and removal based on assessment of 
adverse events, and to determine the feasibility of microdevice 
analysis based on the ability to place and retrieve the device with 
sufficient tissue, of sufficient quality, for downstream histopathology 
analysis and interpretation of at least 80% of the device reservoirs.  
SECONDARY 
ENDPOINTS 
The secondary endpoint is feasibility testing for evaluation of local 
improvement in lesional rash-affected skin with clinically relevant 
skin inflammation treating agents using quantitative histopathologic 
assessment, immunofluorescence, and/or transcriptional profiling of 
skin tissue. This endpoint is appropriate as it directly addresses the 
study’s eventual goal of measuring local improvement in lesional 
rash-affected skin. 
 
OTHER 
EVALUATIONS 
 
SAFETY 
EVALUATIONS 
Safety and feasibility of device placement and harvesting will be 
assessed per the criteria for the primary objectives. Additional safety 

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and feasibility parameters will be documented for the retrieval 
process, including: 
1. Any adverse events associated with the percutaneous retrieval 
procedure. 
2. Any technical challenges or complications with the process of 
device retrieval. 
3. Any logistical or workflow challenges with the device retrieval 
procedure. 
4. Re-evaluation of biopsy site at follow-up visit in 14 days for wound 
infection. 
 
PLANNED INTERIM 
ANALYSES  
When approximately 50% of patients have completed the study 
through Visit 2, an interim analysis for safety will be conducted by the 
investigator. Serious adverse events will be monitored by on an 
ongoing basis throughout the study. 
STATISTICS 
Primary Analysis Plan 
The small region of tissue removed from the rash will be analyzed by 
multi-parameter immunohistochemistry (IHC), immunofluorescence 
(IF) and/or spatial transcriptomics to determine the anti-inflammatory 
effects of each drug being evaluated on the device at the end of the 
device implantation period.  
 
The transcriptomic analysis will be normalized and compared in 
microdose treated wells vs mock treated wells and differential 
expression discerned at a significance level of 5% in a single test, in a 
two-group comparison, using a Negative Binomial mode. Although 
the main goal here is qualitative analysis to assess whether IHC, IF, or 
transcriptomic approaches can be utilized on the acquired tissue 
samples. 
Rationale for Number 
of Subjects 
An initial cohort of at least 20 patients will have all their devices 
removed to initially establish the safety and feasibility of device 
placement and surgical retrieval, as well as post-retrieval processing 
and analysis.  Safety and feasibility of device placement and 
harvesting will be assessed per the criteria for the primary objectives. 
Based on the results of these first 20 patients, subsequent enrolled 
patients in expansion cohort 2 will be selected based on having 
adequate thickness of skin lesions. 
 

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1. BACKGROUND 
The product to be studied is an investigational microdevice designed for in situ drug 
testing atopic dermatitis and psoriasis. The device, measuring 750µm in diameter and 
5mm in length, contains up to 20 drug-loaded reservoirs for percutaneous delivery. Its 
feasibility and safety will be assessed for predicting local cutaneous responses to standard-
of-care therapies and exploring correlations with transcriptomic features and clinical 
outcomes in a pilot study. 
Several IND protocols utilize this in situ therapy testing microdevice for cancers, the most 
relevant being IND #141449 (Principal Investigator: Dr. Oliver Jonas) for its utilization in 
cutaneous T-cell lymphoma, a type of skin cancer. We are adapting use of this in situ 
therapy testing microdevice to test therapies in atopic dermatitis and psoriasis (see letter of 
authorization to refer to IND #141449 from Oliver Jonas, PI). The differences in this 
study and the reference study IND 141449 do not pose new risks or potential adverse 
events. In addition, this same in situ therapy testing microdevice is used in UCSF IRB 
#23-38782.   
A microdevice capable of testing the local in-vivo response to many distinct drug 
compounds or combinations by releasing microdoses of each into distinct regions of tissue 
is currently being utilized in cancer clinical trials. We aim to adapt this device for 
utilization in atopic dermatitis and psoriasis. Analyzing the tissue near the device enables 
assessment of local drug efficacy for each reservoir. The doses of the drugs and biologic 
products will not be increased under this protocol. 
 
The microdevice is a small construct of cylindrical shape measuring 750µm in diameter 
and 5mm in length which houses up to 20 reservoirs (Notes Section 1, Figure 1). It is 
made of PEEK (poly-ether-ether-ketone), a biocompatible material used in other 
implantable constructs including joint replacements. PEEK has been shown to be safe for 
long-term residence in the body, and implantable medical devices made of the same 
materials have been FDA-approved for long-term use in patients. The microdevice is 
radio-opaque and can be visualized by x-ray, CT, ultrasound, and MRI. The device is 
nonferromagnetic and MRI-compatible.    
 
Each of the reservoirs is loaded with a unique drug or combination of drugs, which are 
released into a small (non-overlapping) region of rash-affected skin. After the incubation 
period (typically 72 +/- 24 hours), the device is retrieved with surrounding tissue and this 
specimen is processed and analyzed (Notes Section 2, Figure 3). Crosstalk between drugs 
from different reservoirs is eliminated by appropriate spatial separation of reservoirs and 
by drug and matrix formulation to limit local drug diffusion. In this manner, the anti-
inflammatory effect from each reservoir can be analyzed independently and by pathway-
specific markers. Importantly, drug amounts per reservoir are typically less than 
1/100,000 of the systemic dose given for each drug and therefore the risk of systemic 
toxicity is negligible (Notes Section 3).  
 

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In this study, the microdevice will have a guidewire attached to one end that will extend 
outside the participant’s body. (Notes Section 2, Figure 2 and Figure 3). This guidewire 
will aid in device localization and minimally invasive and surgical retrieval procedures. 
The guidewire is a 0.004” NiTi (“nitinol”) semi-flexible wire of up to 15cm in length. 
This particular wire is super-elastic and robust and is resistant to kinking. Nitinol is a 
nickel-titanium alloy, which is considered safe for long-term implantation and is currently 
used in many interventional devices, including implantable venous filters, vascular stents, 
and vascular guidewires. As nickel is a common contact allergen, to minimize any risk of 
a local cutaneous allergic contact dermatitis, the wire will be secured to the skin with 
underlying gauze in participants with a known nickel allergy.  
 
1.1 
Overview of Non-Clinical Studies 
This microdevice was used in a murine model of human melanoma, breast, and prostate 
cancer and was shown to predict systemic efficacy across multiple tumor models. It also 
demonstrated the ability to assay drug effect locally and show excellent predictive value 
for systemic efficacy for a range of anti- cancer drugs and tumor models. (Jonas, O., 
Landry, H. M., Fuller, J. E., Santini, J. T., Jr, Baselga, J., Tepper, R. I., Cima, M. J., & 
Langer, R. (2015). An implantable microdevice to perform high-throughput in vivo drug 
sensitivity testing in tumors. Science translational medicine, 7(284), 284ra57. 
https://doi.org/10.1126/scitranslmed.3010564.) 
Furthermore, this microdevice technology utilized paclitaxel and doxorubicin in a patient-
derived murine model of breast cancer and showed that the microdevice response 
correlated directly with the systemic drug response in this model for each of the drugs 
tested. (Tatarova, Z., et al  (2022). A multiplex implantable microdevice assay identifies 
synergistic combinations of cancer immunotherapies and conventional drugs. Nature 
Biotechnology, 40(12), 1823–1833.) 
1.2 
Overview of Clinical Studies 
This in situ microdevice was utilized in six patients with high grade gliomas, who 
received drug releasing intratumoral microdevices containing temozolomide, lomustine, 
irinotecan, carboplatin, lapatinib, osimertinib, abemaciclib, everolimus, and doxorubicin. 
This study demonstrated the safety of usage of intratumoral microdevices and their 
efficacy in obtaining patient specific drug response profiling. None of the enrolled patients 
experienced either immediate (within 48 hours after surgery) or delayed (within 30 days) 
adverse events related to the microdevice. All twelve out of the twelve microdevices were 
successfully retrieved from the patient, and bloodwork remained stable before and after 
the operation. (Peruzzi P et al. Intratumoral drug-releasing microdevices allow in situ 
high-throughput 
pharmaco 
phenotyping 
in 
patients 
with 
gliomas. Sci 
Transl 
Med 2023;15(712):eadi0069.) 
 
An additional study further demonstrated the safety and feasibility of this implantable 
microdevices in patients with non-small cell lung cancer undergoing resection. In this 
study, the microdevice contained 12 chemotherapeutic drugs, and was inserted into tumors 

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and successfully retrieved 13 out of the 14 times. The last microdevice remaining did not 
cause any adverse effects. There were no severe adverse reactions observed in the 
patients, and bloodwork revealed no detection of chemotherapeutic agents, allowing for 
high-throughput localized drug delivery. (Tsai LL et al. First-in-Human Intrathoracic 
Implantation of Multidrug-Eluting Microdevices for In Situ Chemotherapeutic Sensitivity 
Testing as Proof of Concept in Nonsmall Cell Lung Cancer. Ann Surg 2023;277(5):e1143-
e1149.) 
2. STUDY RATIONALE 
Studying the microdevice in patients with atopic dermatitis or psoriasis addresses 
challenges in assessing local cutaneous responses to treatments without systemic 
toxicities. Given that moderate-to-severe rash affected patients fail to adequately respond 
to targeted therapies ~20-40% of the time, this novel approach aims to predict individual 
patient responses and personalize treatment strategies. If this approach is successful, it 
would decrease costs (biologic targeted therapies average ~$30,000-40,000/year) and 
minimize systemic adverse effects that occur with immunosuppression, as well as 
decrease the time until a patient achieves successful response to skin therapy. This 
information is crucial for advancing personalized therapies and understanding the 
correlation between local drug responses and clinical outcomes in these inflammatory 
conditions. 
2.1 Risk / Benefit Assessment 
Risks associated with the microdevice will be mitigated through minimally invasive 
procedures, careful localization, and local anesthesia. The potential benefits, including 
personalized treatment insights without systemic toxicities, outweigh procedural risks. 
The study builds on successful trials and ongoing safety assessments, justifying the 
manageable risks for valuable contributions to treatment strategies. 
3. STUDY OBJECTIVES 
3.1 Primary Objective 
The primary objectives are to evaluate the safety of microdevice placement and removal 
based on assessment of adverse events, and to determine the feasibility of microdevice 
analysis based on the ability to place and retrieve the device with sufficient tissue, of 
sufficient quality, for downstream histopathology analysis and interpretation of at least 
80% of the device reservoirs.  
 
3.2 Secondary Objectives 
The secondary objectives are to test feasibility of utilizing quantitative histopathologic 
assessment and/or transcriptional profiling to determine whether there is local 
improvement in lesional rash-affected skin with clinically relevant skin inflammation 
treating agents.   

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4. STUDY DESIGN 
4.1 Study Overview 
This is prospective pilot study evaluating the safety and feasibility of an investigational 
microdevice for in situ drug testing in patients with atopic dermatitis and psoriasis.  The 
pilot study will determine the feasibility of using an in situ microdevice to measure local 
lesional rash-affected skin response to FDA-approved treatments used for atopic 
dermatitis and psoriasis. The microdevice is a drug delivery chamber smaller than a grain 
of rice with reservoirs that delivers up to 20 drugs of any class (small molecules and 
monoclonal antibodies) into spatially distinct regions of a rash, matching intra-lesional 
skin concentrations to those from systemic dosing. This allows for direct assessment of 
local cutaneous responses. It is delivered percutaneously and retrieved 72 hours after 
implantation by excising the device along with surrounding tissue through use of a 
standard 6 mm skin punch biopsy tool. This device allows testing of a range of relevant 
drugs directly inside the actual rash-affected skin, preserving the native rash physiology 
and, importantly, avoiding systemic toxicities. This study will aim to establish the 
feasibility of clinical application of an in situ candidate drug screening microdevice in 
atopic dermatitis and psoriasis, and the potential ability of the device to predict cutaneous 
response to standard of care. 
 
 
The primary objectives are to evaluate the safety of microdevice placement and removal 
based on assessment of adverse events, and to determine the feasibility of microdevice 
analysis based on the ability to place and retrieve the device with sufficient tissue, of 
sufficient quality, for downstream histopathology analysis and interpretation of at least 
80% of the device reservoirs. The secondary objectives are to test feasibility of utilizing 
quantitative histopathologic assessment and/or transcriptional profiling to determine 
whether there is local improvement in lesional rash-affected skin with clinically relevant 
skin inflammation treating agents. The study aims to establish the potential clinical 
application of the microdevice in predicting systemic responses to standard-of-care 
therapies. 
 
Device placement: 
The small size of the microdevice enables its placement via a percutaneous approach 
using an 18-gauge needle, a fraction of the size compared to standard punch tools for skin 
biopsies. For more information, please see Notes Section 2. 
 
After placement, the microdevice will dwell in the tissue for approximately ~72 hours, 
enabling micro-doses of drugs to be released from the reservoirs and elicit local 
inflammatory responses.  
 
Device retrieval: 
To analyze the effects on the tissue, the microdevice will be removed along with a rim of 
intact surrounding tissue. Microdevice retrieval can be achieved through two approaches, 

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using dermatologic procedural techniques, similar to obtaining a skin punch biopsy, or 
surgical excision (as a backup). Given the straightforward nature and minimal risk 
involved in utilizing a 6 mm punch biopsy tool, this technique will be employed for 
microdevice retrieval. In the event the punch biopsy tool cannot retrieve the microdevice 
in totality, participants may undergo surgical excision of skin with embedded 
microdevice. For more information, please see Notes Section 2.  
 
5. CRITERIA FOR EVALUATION 
5.1 Primary Efficacy Endpoint 
The primary endpoint is the evaluation of the safety and feasibility of the microdevice, 
specifically assessing adverse events associated with device placement and removal. This 
endpoint will be assessed from baseline to the completion of the microdevice retrieval, 
which occurs approximately 72 +/- 24 hours after implantation. This endpoint is 
appropriate as it directly addresses the study's primary objective of evaluating the safety 
of microdevice placement and removal based on assessment of adverse events, and to 
determine the feasibility of microdevice analysis based on the ability to place and retrieve 
the device with sufficient tissue, of sufficient quality, for downstream histopathology 
analysis and interpretation of at least 80% of the device reservoirs.  
5.2 Secondary Efficacy Endpoints 
The secondary endpoint is the evaluation of local improvement in lesional rash-affected 
skin with clinically relevant skin inflammation treating agents using quantitative 
histopathologic assessment, immunofluorescence, and/or transcriptional profiling of skin 
tissue. This endpoint is appropriate as it directly addresses the study’s eventual goal of 
measuring local improvement in lesional rash-affected skin. 
5.3 Safety Evaluations 
The safety evaluations in the study include: 
1. Adverse Events Assessment: 
   - Monitor and record adverse events associated with microdevice placement and 
retrieval procedures. 
2. Technical Challenges or Complications: 
   - Document any technical challenges or complications during the device retrieval 
process. 
3. Logistical or Workflow Challenges: 
   - Assess any logistical or workflow challenges related to the device retrieval procedure. 
4. Complications of Microdevice Placement: 
   - Evaluate for any complications arising from the microdevice placement, as assessed by 
a dermatologist. 

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5. Interim Adverse Events Monitoring: 
   - Monitor for any intercurrent adverse events following microdevice placement and 
record them. 
Rationale: These safety evaluations aim to comprehensively assess the safety profile of 
the microdevice, covering adverse events, technical aspects, and logistical considerations 
associated with both placement and retrieval procedures. 
Importantly, drug amounts per reservoir are typically less than 1/100,000 of the systemic 
dose given for each drug and therefore the risk of systemic toxicity is negligible (Notes 
Section 3). Thus, it is not necessary to evaluate the safety of each drug or biologic 
individually.  
 
6. SUBJECT SELECTION 
6.1 Study Population 
The subject population consists of 20 individuals diagnosed with atopic dermatitis or 
psoriasis who are over the age of 18, with considerations for the suitability of skin lesions 
for microdevice placement. Exclusion criteria may apply for safety and feasibility reasons. 
6.2 Inclusion Criteria 
A confirmed diagnosis of atopic dermatitis or psoriasis, and the presence of suitable skin 
lesions for microdevice placement. Written informed consent (and assent when 
applicable) obtained from subject or subject’s legal representative and ability for subject 
to comply with the requirements of the study. 
6.3 Exclusion Criteria 
Presence of a condition or abnormality that in the opinion of the Investigator would 
compromise the safety of the patient or the quality of the data. 
7. CONCURRENT MEDICATIONS 
All subjects should be maintained on the same medications throughout the entire study 
period, as medically feasible, with no introduction of new chronic therapies. 
7.1 Allowed Medications and Treatments 
All 
7.2 Prohibited Medications and Treatments 
None 

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8. STUDY TREATMENTS 
8.1 Method of Assigning Subjects to Treatment Groups 
There is only one treatment group. 
8.2 Blinding 
There is no blinding or need for blinding in this study. 
8.3 Formulation of Test and Control Products 
See Notes Section 3 and below for more details. 
8.3.1 Formulation of Test Product 
For this pilot study, the drugs used in the study will include standard medications used for 
treatment of atopic dermatitis and psoriasis. All the drugs are FDA approved for use in 
patients. The in situ microdevice will contain a subset of the following: Triamcinolone, 5-
fluorouracil, Calcipotriene, Tapinarof, Crisaborole, Tacrolimus, Adalimumab, Etanercept, 
Certolizumab, Infliximab, Secukinumab, Ixekizumab, Apremilast, Risankizumab, 
Ustekinumab, Hydroxychloroquine, Methotrexate, Mycophenolate, Azathioprine, 
Chloroquine, Cyclosporine, Tofacitinib, Deucravacitinib, Dupilumab, Tralokinumab, 
Guselkumab, Tildrakizumab, Baractinib, Abrocitinib, Upadacitinib, Lebrikizumab, 
Nemolizumab, Ruxolitinib, Bimekizumab, Roflumilast. 
 
See Notes Section 3 for further details.  
8.3.2 Formulation of Control Product 
Pure PEG (polyethylene glycol) will be used as a control. 
8.3.3 Packaging and Labeling 
Each microdevice will harbor up to 19 FDA-approved drugs relevant to the treatment of 
atopic dermatitis and psoriasis, including those that are standard-of-care. Each drug or 
drug combination will be released from multiple, separate reservoirs. One reservoir will 
harbor a drug vehicle (PEG) only. For this pilot study, the drugs used in the study will 
include standard agents used for treatment of atopic dermatitis and psoriasis. All the drugs 
must be FDA approved for use in patients. In future studies, additional investigational 
drugs may be added via appropriate procedures. 
8.4 Supply of Study Drug at the Site 
Drugs will be paid for by the study and will be purchased through the research pharmacy. 
There will be no charge to patients for the drugs used in this study. 

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8.4.1 Dosage/Dosage Regimen 
Microdevice Description: The microdevice is a small construct measuring 750μm in 
diameter and 5mm in length (Notes Section 1, Figure 1). It contains up to 20 reservoirs, 
each loaded with a unique drug or combination of drugs. The drugs are released into 
small, non-overlapping regions.  
8.4.2 Dispensing 
Drug Delivery: The microdevice is placed percutaneously using an 18-gauge needle. Once 
placed, it remains in the tissue for approximately 72 +/- 24 hours, allowing microdoses of 
drugs to be released from the reservoirs and elicit local responses. 
8.4.3 Administration Instructions  
The device and medication will be administered by the investigators. See Notes Section 3 
for further details. 
8.4.4 Storage 
Loaded Microdevice will be stored at 4ºC in either UCSF research pharmacy or DFCI 
pharmacy. 
8.5 Study Drug Accountability 
An accurate and current accounting of the dispensing of study drug for each subject will 
be maintained on an ongoing basis by a member of the study site staff. The number of 
study drug dispensed by the subject will be recorded on the Investigational Drug 
Accountability Record. The study monitor will verify these documents throughout the 
course of the study. 
9. STUDY PROCEDURES AND GUIDELINES 
A Schedule of Events representing the required testing procedures to be performed for the 
duration of the study is diagrammed in Appendix 1. 
Prior to conducting any study-related activities, written informed consent and the Health 
Insurance Portability and Accountability Act (HIPAA) authorization must be signed and 
dated by the subject.   
9.1 Clinical Assessments 
9.1.1 Concomitant Medications 
All concomitant medication and concurrent therapies will be documented at 
Baseline/Screening and at early termination when applicable. Dose, route, unit frequency 
of administration, and indication for administration and dates of medication will be 
captured. 
9.1.2 Demographics  
Demographic information (date of birth, gender, race) will be recorded at Screening.  

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9.1.3 Medical History  
Relevant medical history, including history of current disease, other pertinent respiratory 
history, and information regarding underlying diseases will be recorded at Screening. 
9.1.4 Physical Examination 
A skin examination will be performed by either the investigator or a sub investigator who 
is a physician at Screening.  
9.1.5 Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. 
Duration (start and stop dates), outcome, treatment and relation to study drug will be 
recorded on the case report form (CRF).  
10. EVALUATIONS BY VISIT 
10.1 Visit 1. Screening Visit and Device Placement: *For more information on device 
placement, please see Notes Section 2* 
1. Identification of eligible patients with confirmed atopic dermatitis or psoriasis. 
2. Review the study with the subject (or subject’s legal representative) and obtain written 
informed consent and HIPAA authorization and assent, if appropriate. 
3. Assign the subject a unique screening number. 
4. Record demographics data. 
5. Record medical history, including history of rash, diagnosis date, and prior treatments. 
6. Record concomitant medications. 
7. Perform a skin examination. 
8. Percutaneous placement of microdevices (1 each in 2 separate skin lesions, totaling 2 
microdevices per patient) with local anesthesia (1% lidocaine with 1:100,000 epinephrine) 
administered intra-dermally, careful taping of the guidewire to the skin, covered with a 
sterile bandage to prevent dislodgement. 
9. Monitoring of the patient for a short time (15 minutes) after device placement. 
10. Patients will be provided with verbal and written instructions and a phone number to call 
with questions after discharge. Female patients of childbearing age will be instructed that 
they should continue current oral contraceptive pills or intrauterine device for 30 days 
after the device retrieval visit. 
 
10.2 Visit 2. Device Retrieval Visit: (Approximately 72 +/- 24 hours after device 
implantation) *For more information on device retrieval, please see Notes Section 2* 
1. Scheduled for approximately 72 +/- 24 hours after device implantation. 
2. Evaluation by a dermatologist to assess adverse events. 
3. Percutaneous retrieval of microdevices using a 6 mm skin biopsy punch tool. 
4. Clean skin. Local anesthesia (1% lidocaine with 1:100,000 epinephrine) delivered in a 
ring block via a 30-gauge needle. 

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5. Take sample(s), place suture. Patient will be offered either absorbable sutures (does not 
require follow up visit), offered a suture removal kit (to remove stiches at home by 
themselves), or have a follow up visit lasting for a few minutes to remove sutures.  
6. If retrieval via punch biopsy tool is unsuccessful, patients may undergo surgical excision. 
In patients needing surgical excision, the procedure will be scheduled to occur within 14 
days of the implantation. 
7. Post-retrieval assessment of adverse events. 
8. Discharge instructions for home care. 
 
Optional: Visit 3 (~2 weeks after Visit #2) 
1.  Remove suture. 
2. Inspect biopsy site(s) to rule out infection. 
3. Record any adverse experiences 
4. Alternatively, this visit can be skipped, and the patient will be provided with a suture removal 
kit and can self-remove sutures (this is an option that we provide to patients in clinical practice to 
minimize inconvenience of a return visit for suture removal only) 
 
11. ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
11.1 Adverse Events 
An adverse event (AE) is any untoward medical occurrence in a clinical investigation of a 
patient administered a pharmaceutical product and that does not necessarily have a causal 
relationship with the treatment. An AE is therefore any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom or disease temporally associated 
with the administration of an investigational product, whether or not related to that 
investigational product.  An unexpected AE is one of a type not identified in nature, 
severity, or frequency in the current Investigator’s Brochure or of greater severity or 
frequency than expected based on the information in the Investigator’s Brochure. 
The Investigator will probe, via discussion with the subject, for the occurrence of AEs 
during each subject visit and record the information in the site’s source documents.  
Adverse events will be recorded in the patient CRF. Adverse events will be described by 
duration (start and stop dates and times), severity, outcome, treatment and relation to 
study drug, or if unrelated, the cause. 
AE Severity 
The National Cancer Institute’s Common Terminology Criteria for Adverse Events 
(CTCAE) Version 3.0 should be used to assess and grade AE severity, including 
laboratory abnormalities judged to be clinically significant. The modified criteria can be 
found in the study manual. If the experience is not covered in the modified criteria, the 
guidelines shown in Table 1 below should be used to grade severity. It should be pointed 
out that the term “severe” is a measure of intensity and that a severe AE is not necessarily 
serious. 

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Table 1.  AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
Transient or mild discomfort; no limitation in activity; no medical 
intervention or therapy required. The subject may be aware of the sign 
or symptom but tolerates it reasonably well. 
Moderate (2) 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. 
Severe (3) 
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible. 
Life-threatening (4) 
The subject is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe. 
 
11.2 Serious Adverse Experiences (SAE) 
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes: 
• 
death 
• 
a life-threatening adverse experience 
• 
inpatient hospitalization or prolongation of existing hospitalization 
• 
a persistent or significant disability/incapacity 
• 
a congenital anomaly/birth defect  
Other important medical events may also be considered an SAE when, based on 
appropriate medical judgment, they jeopardize the subject or require intervention to 
prevent one of the outcomes listed.  
 
11.2.1 Serious Adverse Experience Reporting 
Study sites will document all SAEs that occur (whether or not related to study drug) per 
UCSF CHR Guidelines.  The collection period for all SAEs will begin after informed 
consent is obtained and end after procedures for the final study visit have been completed. 
 
In accordance with the standard operating procedures and policies of the local Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC), the site investigator will report 
SAEs to the IRB/IEC.   
11.3 Medical Monitoring 
Dr. Raymond J. Cho should be contacted directly at this number to report medical 
concerns or questions regarding safety. Phone: (650)520-0208. 
   

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12. DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
12.1 Early Discontinuation of Study Device  
A subject may be discontinued from study treatment at any time if the subject or the 
investigator feels that it is not in the subject’s best interest to continue. The following is a 
list of possible reasons for study treatment discontinuation:  
- 
Subject withdrawal of consent 
- 
Subject is not compliant with study procedures 
- 
Adverse event that in the opinion of the investigator would be in the best interest 
of the subject to discontinue study treatment  
All subjects who discontinue study treatment should come in for an early discontinuation 
visit as soon as possible and then should be encouraged to complete all remaining 
scheduled visits and procedures.  
All subjects are free to withdraw from participation at any time, for any reason, specified 
or unspecified, and without prejudice.  
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals. The reason for the subject’s withdrawal from the study will be specified in 
the subject’s source documents.  
12.2 Withdrawal of Subjects from the Study 
A subject may be withdrawn from the study at any time if the subject or the investigator 
feels that it is not in the subject’s best interest to continue.  
All subjects are free to withdraw from participation at any time, for any reason, specified 
or unspecified, and without prejudice.  
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals. The reason for the subject’s withdrawal from the study will be specified in 
the subject’s source documents. Subjects who discontinue study treatment early should 
still be offered a visit for suture removal.  
12.3 Replacement of Subjects 
Subjects who withdraw from the study will be replaced.  
13. PROTOCOL VIOLATIONS 
A protocol violation occurs when the subject, investigator fails to adhere to significant 
protocol requirements affecting the inclusion, exclusion, subject safety and primary 

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endpoint criteria. Protocol violations for this study include, but are not limited to, the 
following:  
- 
Failure to meet inclusion/exclusion criteria  
- 
Failure to comply with Good Clinical Practice (GCP) guidelines 
The investigator Raymond Cho will determine if a protocol violation will result in 
withdrawal of a subject.  
When a protocol violation occurs, it will be discussed with the investigator and a Protocol 
Violation Form detailing the violation will be generated. This form will be signed by the 
Investigator. A copy of the form will be filed in the site’s regulatory binder.  
14. STATISTICAL METHODS AND CONSIDERATIONS 
Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will 
be written describing all analyses that will be performed. The SAP will contain any 
modifications to the analysis plan described below.  
14.1 Data Sets Analyzed  
All eligible patients who consent to the study and have a skin sample taken will have data 
analyzed.  
14.2 Demographic and Baseline Characteristics  
The following demographic variables at screening will be summarized: race, gender, age, 
rash type and biopsy site.  
14.3 Analysis of Primary Endpoint  
Safety and tolerability data will be summarized. Postoperative follow up for each patient 
will be performed, and adverse events associated with device placement and removal will 
be tabulated and will include the number of patients for whom the event occurred, the rate 
of occurrence, and the severity and relationship to study device. This endpoint will be 
assessed from baseline to the completion of the microdevice retrieval, which occurs 
approximately 72 +/- 24 hours after implantation. 
14.4 Analysis of Secondary Endpoints 
Histopathologic assessment will measure local cutaneous response to anti-inflammatory 
agents using histopathologic assessment. We will perform concomitant genomic, 
immunofluorescence, and transcriptomic analysis with assessment of local drug response 
to explore whether the skin/microdevice samples provide adequate tissue of sufficient 
quality for these types of analyses. 

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Devices left in place longer than 104 hours will not be included in the data analysis but 
may be removed with subsequent surgical procedures (up to 14 days later), although the 
biomaterials of the microdevice are acceptable from a safety standpoint for long-term 
dwelling in tissue.  
14.5 Sample Size and Randomization 
There will be 20 patients. This is a non-randomized study.  
15. DATA COLLECTION, RETENTION AND MONITORING 
15.1 Data Collection Instruments  
The Investigator will prepare and maintain adequate and accurate source documents 
designed to record all observations and other pertinent data for each subject treated with 
the study drug.  
Study personnel at each site will enter data from source documents corresponding to a 
subject’s visit into the protocol-specific paper CRF when the information corresponding to 
that visit is available. Subjects will not be identified by name in the study database or on 
any study documents to be collected by the investigator but will be identified by 
deidentified subject number. If a correction is made on a CRF, the study staff member will 
line through the incorrect data, write in the correct data and initial and date the change.  
The Investigator is responsible for all information collected on subjects enrolled in this 
study. All data collected during the course of this study must be reviewed and verified for 
completeness and accuracy by the Investigator. A copy of the CRF will remain at the 
Investigator’s site at the completion of the study.  
15.2 Data Management Procedures 
The data will be entered into a validated database.  The Data Management group will be 
responsible for data processing, in accordance with procedural documentation.  Database 
lock will occur once quality assurance procedures have been completed. 
All procedures for the handling and analysis of data will be conducted using good 
computing practices meeting FDA guidelines for the handling and analysis of data for 
clinical trials. 
15.3 Availability and Retention of Investigational Records  
The Investigator must make study data accessible to the monitor, other authorized 
representatives of the Study funder (or designee), IRB/IEC, and Regulatory Agency (e.g., 
FDA) inspectors upon request. A file for each subject must be maintained that includes the 
signed Informed Consent, HIPAA Authorization Form and copies of all source 
documentation related to that subject. The Investigator must ensure the reliability and 
availability of source documents from which the information on the CRF was derived. 

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Leftover biological specimens may be saved for future research with optional ICF patient 
consent.  
15.4 Subject Confidentiality  
In order to maintain subject confidentiality, only a subject number will identify all study 
subjects on CRFs and other documentation submitted to the Study funder. Additional 
subject confidentiality issues (if applicable) are covered in the Clinical Study Agreement. 
Study funder will only receive deidentified data.  
16. ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
The study will be conducted according to the Declaration of Helsinki, Protection of 
Human Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and 
Obligations of Clinical Investigators (21 CFR 312). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number and initials only.  All study records will be 
kept in a locked file cabinet and code sheets linking a patient’s name to a patient 
identification number will be stored separately in another locked file cabinet.  Clinical 
information will not be released without written permission of the subject, except as 
necessary for monitoring by the FDA.  The Investigator must also comply with all 
applicable privacy regulations (e.g., Health Insurance Portability and Accountability Act 
of 1996, EU Data Protection Directive 95/46/EC). 
16.1 Protocol Amendments 
Any amendment to the protocol will be written by the investigator. Protocol amendments 
cannot be implemented without prior written IRB/IEC approval except as necessary to 
eliminate immediate safety hazards to patients.  A protocol amendment intended to 
eliminate an apparent immediate hazard to patients may be implemented immediately, 
provided the IRBs are notified within five working days. 
16.2 Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the IRB/IEC of each 
participating center prior to study initiation.  Serious adverse experiences regardless of 
causality will be reported to the IRB/IEC in accordance with the standard operating 
procedures and policies of the IRB/IEC, and the Investigator will keep the IRB/IEC 
informed as to the progress of the study.  The Investigator will obtain assurance of 
IRB/IEC compliance with regulations. 
Any documents that the IRB/IEC may need to fulfill its responsibilities (such as protocol, 
protocol amendments, Investigator’s Brochure, consent forms, information concerning 
patient recruitment, payment or compensation procedures, or other pertinent information) 
will be submitted to the IRB/IEC.  The IRB/IECs written unconditional approval of the 
study protocol, and the informed consent form will be in the possession of the Investigator 
before the study is initiated.  The IRB/IECs unconditional approval statement will be 
transmitted by the Investigator to Study funder prior to the shipment of study supplies to 

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the site.  This approval must refer to the study by exact protocol title and number and 
should identify the documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without 
prior written IRB/IEC approval except when necessary to eliminate immediate hazards to 
the patients or when the change(s) involves only logistical or administrative aspects of the 
study.  Such modifications will be submitted to the IRB/IEC and written verification that 
the modification was submitted and subsequently approved should be obtained.   
The IRB/IEC must be informed of revisions to other documents originally submitted for 
review; serious and/or unexpected adverse experiences occurring during the study in 
accordance with the standard operating procedures and policies of the IRB; new 
information that may affect adversely the safety of the patients of the conduct of the study; 
an annual update and/or request for re-approval; and when the study has been completed. 
16.3 Informed Consent Form  
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH 
GCP, US Code of Federal Regulations for Protection of Human Subjects (21 CFR 
50.25[a,b], CFR 50.27, and CFR Part 56, Subpart A), the Health Insurance Portability and 
Accountability Act (HIPAA, if applicable), and local regulations. 
The Investigator will prepare the informed consent form, assent and HIPAA authorization 
and provide the documents to the Sponsor or designee for approval prior to submission to 
the IRB/IEC.  The consent form generated by the Investigator must be acceptable to the 
Sponsor and be approved by the IRB/IEC.  The written consent document will embody the 
elements of informed consent as described in the International Conference on 
Harmonisation and will also comply with local regulations. The Investigator will send an 
IRB/IEC-approved copy of the Informed Consent Form to the Sponsor (or designee) for 
the study file. 
A properly executed, written, informed consent will be obtained from each subject prior to 
entering the subject into the trial.  Information should be given in both oral and written 
form and subjects must be given ample opportunity to inquire about details of the study.  
If appropriate and required by the local IRB/IEC, assent from the subject will also be 
obtained.  If a subject is unable to sign the informed consent form (ICF) and the HIPAA 
authorization, a legal representative may sign for the subject.   A copy of the signed 
consent form (and assent) will be given to the subject and the original will be maintained 
with the subject’s records. 
16.4 Publications  
The preparation and submittal for publication of manuscripts containing the study results 
shall be in accordance with a process determined by mutual written agreement among the 
study Sponsor and participating institutions.  The publication or presentation of any study 
results shall comply with all applicable privacy laws, including, but not limited to, the 
Health Insurance Portability and Accountability Act of 1996.  

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16.5 Investigator Responsibilities 
By signing the Agreement of Investigator form, the Investigator agrees to: 
1. Conduct the study in accordance with the protocol and only make changes after 
notifying the Sponsor (or designee), except when to protect the safety, rights or 
welfare of subjects. 
2. Personally conduct or supervise the study (or investigation). 
3. Ensure that the requirements relating to obtaining informed consent and IRB review 
and approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. Report to the Sponsor or designee any AEs that occur in the course of the study, in 
accordance with §21 CFR 312.64. 
5. Ensure that all associates, colleagues and employees assisting in the conduct of the 
study are informed about their obligations in meeting the above commitments. 
6. Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to 
make those records available for inspection with the Sponsor (or designee). 
7. Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be 
responsible for initial and continuing review and approval of the clinical study. 
8. Promptly report to the IRB and the Sponsor (or designee) all changes in the research 
activity and all unanticipated problems involving risks to subjects or others (to 
include amendments and IND safety reports). 
9. Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients/subjects. 
10. Comply with all other requirements regarding the obligations of clinical investigators 
and all other pertinent requirements listed in § 21 CFR part 312. 
 

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APPENDIX 1.  SCHEDULE OF STUDY VISITS 
 
VISIT 1 
Screening Visit and Device 
Placement 
VISIT 2 
Device Retrieval Visit 
(72 +/- 24 hours after device 
placement) 
VISIT 3  
Optional Suture Removal Visit 
(~2 weeks after Visit 2) 
 
Informed Consent 
X 
 
 
Demographics Data 
X 
 
 
Medical History 
X 
 
 
Concomitant Medications 
X 
 
 
Skin Examination 
X 
X 
 
Placement of Microdevices 
X 
 
 
Monitoring (15 minutes) 
X 
 
 
Adverse Experiences 
 
X 
 
Skin Biopsy  
 
X 
 
Retrieval of Microdevices 
 
X 
 
Provide Verbal and Written Discharge 
Instructions 
X 
X 
 
(If applicable) Schedule surgical excision 
procedure within 14 days of implantation 
 
X 
 
Suture removal and biopsy site check 
 
 
X 
 
 
 
 
 
 
 
 

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NOTES:  
 
Section 1: Concept for in-vivo drug sensitivity assay and description of 
device 
The microdevice is a drug delivery chamber smaller than a grain of rice with reservoirs that 
delivers up to 20 drugs of any class (small molecules and monoclonal antibodies) into 
spatially distinct regions of a rash, matching intra-lesional skin concentrations to those 
from systemic dosing. This allows for direct assessment of local cutaneous responses. 
During implantation, drugs diffuse into confined regions. Each such region can be assayed 
independently to assess the specific response of a given drug. Following incubation, a 
second biopsy procedure is administered in which a coring needle selectively retrieves a 
small column of tissue that immediately surrounds the device. This tissue contains the 
regions of drug diffusion and is sufficient for determination of efficacy of drugs. Adapted 
from Jonas, O., Landry, H. M., Fuller, J. E., Santini, J. T., Jr, Baselga, J., Tepper, R. I., 
Cima, M. J., & Langer, R. (2015). An implantable microdevice to perform high-throughput 
in vivo drug sensitivity testing in tumors. Science translational medicine, 7(284), 284ra57. 
https://doi.org/10.1126/scitranslmed.3010564. 
 
Figure 1. Representative depiction of in situ microdevice 
 
 
Section 2: Percutaneous device placement and retrieval 
 
Device Delivery: 
The small size of the microdevice enables its placement via a percutaneous approach using 
an 18-gauge needle, a fraction of the size compared to standard punch tools for skin 
biopsies.  
 
In the current study, a coaxial system comprising a 18G metal outer needle and an inner 
hollow needle stylet will be used for microdevice delivery (see below figure). The 
microdevice is placed at the tip of the delivery needle and the guide wire is coaxially 
placed inside the inner stylet. Bone wax is placed at the tip of the needle, keeping the 
microdevice from prematurely advancing beyond the needle tip. The entire coaxial delivery 
needle is guided to the desired depth determined by markings on the delivery needle, which 
will be no more than 5-6mm deep. Once satisfactory location of the needle is clinically 
assessed by visual examination, the inner stylet is advanced at least 5mm to deploy/release 
the microdevice. The needle and inner stylet is then removed over the guidewire, leaving 

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the microdevice and guidewire in place. The external portion of the guidewire is secured to 
the participant’s skin using a sterile adhesive cover to prevent dislodgement. 
 
Figure 2. 
 
 
 
 
 
After placement, the microdevice will dwell in the tissue for approximately 72 +/- 24 
hours, enabling micro-doses of drugs to be released from the reservoirs and elicit local 
inflammatory responses.  
 
Device retrieval: 
To analyze the effects on the tissue, the microdevice will be removed along with a rim of 
intact surrounding tissue. Microdevice retrieval can be achieved through two approaches, 
using dermatologic procedural techniques, similar to obtaining a skin punch biopsy or 
surgical excision. Given the straightforward nature and minimal risk involved in utilizing a 
punch biopsy tool this technique will be employed for microdevice retrieval. In the event 
the punch biopsy tool cannot retrieve the microdevice in totality, participants may undergo 
surgical excision of skin with embedded microdevice. 
 
The retrieval procedure is as follows: The sterile adhesive covering is removed from the 
participant and the guidewire extending from the participant is straightened. The 6 mm skin 
biopsy punch tool is placed coaxially around the guidewire (see below figure). The biopsy 
tool is advanced to the hub of the tool, ensuring a full thickness biopsy from epidermis to 
subcutaneous fat. Following biopsy device advancement into the participant, the tissue to 
be removed is lift with the use of forceps or the guide wire and cut at the base in the 
subcutaneous fat, allowing sampling/cutting of the tissue surrounding the microdevice. The 
microdevice and tissue is submitted in formalin for histopathologic analysis. 
 
 
 
 
 
 
 
 
Microdevice implantation apparatus: An outer needle houses an inner hollow stylet and an innermost 
guidewire with microdevice at its tip. The microdevice attached to the end of the guidewire is deployed 
into tissue by advancing the inner stylet. This is similar to the mechanism used for deploying fiducial 
markers and brachytherapy seeds. 
Guidewire 
Outer needle (17-19G) 
Microdevice attached to guidewire 
Hollow inner stylet 

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Figure 3. 
 
 
 
 
 
 
 
Section 3: Description, Form, Storage and Stability, Compatibility 
All agents used in this study are FDA approved for use in atopic dermatitis and 
psoriasis. 
3.1 Handling 
Qualified personnel, familiar with procedures that minimize undue exposure to themselves 
and the environment, will undertake the preparation, handling, and safe disposal of the 
chemotherapeutic agent in a self-contained and protective environment. 
3.2 Availability 
Drugs will be obtained directly from the DFCI (Dana Farber Cancer Institute) pharmacy. 
Drugs are commercially available agents available from various manufacturers. The 
specific manufacturer will be determined by the DFCI formulary.   
3.3 Preparation 
The drug will be prepared, mixed with polyethylene glycol matrix, and loaded into the 
microdevice in a sterile manner in the Jonas laboratory at BWH Harvard), using protocols 
developed with the FDA. Each step in the process will be monitored by a research 
pharmacist and recorded on a checklist. Of note, the volume of each reservoir is physically 
limited in capacity so there is a maximum amount of drug solution that can be added per 
reservoir. Pure PEG (polyethylene glycol) will be used in control conditions. 
Microdevice retrieval: Biopsy 
The retrieval device is guided to the edge of the microdevice over the guidewire (image not to scale). 
After satisfactory position of the biopsy device, it will be inserted into the skin to the subcutaneous fat 
around the microdevice to the cut surrounding tissue, and the tissue/microdevice is removed from the 
participant.  

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3.4 Administration  
Drugs will be released from the microdevice into local tissues. The drug will be released 
from the microdevice via passive diffusion, as has been extensively characterized in pre-
clinical studies. The drug will only penetrate the local cutaneous tissues. The duration of 
drug release will be for a period of 72 +/- 24 hours while the microdevice is in the skin prior 
to retrieval. The local tissue is retrieved along with the microdevice, and no residual drug 
will remain. 
 
The drug amounts released from a given reservoir on the microdevice into the skin are 
approximately 1 microgram which is on the order of one-millionth of the systemic dose. 
The FDA defines “micro-doses as <1% of the total systemic dose” and provides 
streamlined approval for human testing of compounds at these doses. The doses released 
from the microdevices are less than a thousandth of what the FDA terms a microdose. 
Additionally, per the microdevice structure and preliminary data, the drugs will only be 
released 300-400 micrometers into the local tissue area. This region containing virtually all 
of the drug is then removed from the body during microdevice retrieval. Nonetheless, even 
if the entire contents of drug in the device were to reach the systemic circulation in some 
manner, they would be many thousands of times less than a physiologically relevant dose 
and therefore would have a minimal impact on the patient.    
 
The microdevice will only remain in place for 72 +/- 24 hours until its removal at surgery.  
3.5 Ordering 
Drugs will be obtained from the DFCI pharmacy or directly from manufacturers. 
3.6 Accountability 
All drugs will be dispensed from the DFCI pharmacy using standard procedures. Drugs 
will be loaded into the microdevice and tracked in detail under the supervision of a research 
pharmacy.  The microdevices containing drug will be tracked during sterilization, transfer, 
and storage until implanted and retrieved from patients. The investigator and clinical 
research team will be responsible for maintaining records of the inventory using standard 
drug accountability forms. 
3.7 Destruction and Return 
Any excess drug at the time of microdevice loading will be disposed of in the research 
pharmacy per standard procedures. Any unused microdevices will be destroyed following 
proper procedures for disposal of biohazardous materials.