Use of Platelet-rich Plasma (PRP) Therapy in Patients With Brittle Nail Syndrome
Phase: PHASE4
Conditions: Nail Diseases
Sponsor: Weill Medical College of Cornell University

Page # i 
TITLE:  Use of Platelet-rich plasma (PRP) therapy in patients with Brittle Nail Syndrome 
IRB Protocol #: 20-07022437 
Version Date: 04/14/2023 
NCT04941807
Principal Investigator: 
Co-Investigators: 
Shari R. Lipner MD, PhD 
Yu Wang BA 
Jose Ricardo MD 
Participating Sites:   
Weill Cornell Dermatology - 1305 York Avenue, NY, NY 10021 

Protocol # 20-07022437 
Version Date: 04/14/2023 
Page # ii 
Table of Contents 
CONFIDENTIALITY STATEMENT ............................................................................................. VI 
LIST OF ABBREVIATIONS ............................................. ERROR! BOOKMARK NOT DEFINED. 
1. PROTOCOL SUMMARY .......................................................................................................... 1 
1.1 
Schema ............................................................................................................................. 3 
1.2 
Study Objectives and End Points .................................................................................. 4 
1.2.1 
Primary Objectives ................................................................................................... 4 
1.2.2 
Secondary Objectives .............................................................................................. 4 
1.2.3 
Exploratory Objectives ............................................................................................ 4 
1.2.4 
Primary Endpoints ................................................................................................... 4 
1.2.5 
Secondary Endpoints .............................................................................................. 4 
2. BACKGROUND ....................................................................................................................... 4 
2.1 
Disease ............................................................................................................................. 4 
2.2 
Investigational Agent/Device, or Surgical Treatment/Method .................................... 4 
2.3 
Rationale .......................................................................................................................... 5 
2.4 
 Risk/Benefit Assessment .............................................................................................. 6 
2.4.1 
Known Potential Risks ............................................................................................ 6 
2.4.2 
Known Potential Benefits ........................................................................................ 6 
2.4.3 
Assessment of Potential Risks and Benefits ........................................................ 6 
3. STUDY DESIGN ....................................................................................................................... 6 
3.1 
Overall Design ................................................................................................................. 6 
3.2 
Scientific Rationale for Study Design ........................................................................... 8 
3.3 
Justification for Dose ...................................................................................................... 9 
3.4 
End of Study Definition ................................................................................................... 9 
4. SUBJECT SELECTION ........................................................................................................... 9 
4.1 
Study Population ............................................................................................................. 9 
4.2 
Inclusion Criteria ............................................................................................................. 9 
4.3 
Exclusion Criteria ............................................................................................................ 9 
4.4 
Lifestyle Considerations ................................................................................................. 9 
4.5 
Screen Failures ................................................................................................................ 9 
4.6 
Strategies for Recruitment and Retention .................................................................. 10 
5. REGISTRATION PROCEDURES .......................................................................................... 10 
5.1 
Subject Registration (WCM only) ................................................................................. 10 
5.2 Subject Registration (Sub-sites) ............................................ Error! Bookmark not defined. 
6. STUDY PROCEDURES ......................................................................................................... 10 
6.1 
Schedule of Assessments ............................................................................................ 10 
6.1.1 
Screening Visit (-X days before start of treatment) ............................................ 11 
6.1.2 
Treatment Phase .................................................................................................... 11 
6.1.2.1 
Visit 1 (baseline; Cycle 1 Day 1) .............................. Error! Bookmark not defined. 
6.1.2.2 
Visit 2 (± X day(s)) ..................................................... Error! Bookmark not defined. 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # iii 
 
6.1.3 
Follow-up Phase ..................................................................................................... 12 
7. STUDY INTERVENTION ........................................................................................................ 12 
7.1 
Study Intervention/Device Description ....................................................................... 12 
7.2 
Availability ..................................................................................................................... 12 
7.3 
Acquisition and Accountability .................................................................................... 12 
7.4 
Formulation, Appearance, Packaging, and Labeling ................................................. 12 
7.5 
Product Storage and Stability ...................................................................................... 12 
7.6 
Preparation .................................................................................................................... 13 
7.7 
Dosing and Administration .......................................................................................... 13 
7.7.1 
Dosing Delays/Dose Modifications ...................................................................... 13 
7.8 
General Concomitant Medication and Supportive Care Guidelines ......................... 13 
7.9 
Duration of Therapy and Criteria for Removal from Study ....................................... 13 
7.10  Duration of Follow Up .................................................................................................... 14 
7.11 Measures to Minimize Bias: Randomization and Blinding .......................................... 14 
7.12 Study Intervention/Follow-up Compliance .................................................................... 14 
8. STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................................ 14 
8.1 
Discontinuation of Study Intervention ........................................................................ 14 
8.2 
Participant Discontinuation/Withdrawal from the Study ........................................... 15 
8.3 
Lost to Follow Up .......................................................................................................... 15 
9. CORRELATIVE/SPECIAL STUDIES ..................................................................................... 15 
9.1 
Laboratory Correlative Studies .................................................................................... 16 
9.1.1 
Title – Laboratory Correlative Study #1 ............................................................... 16 
9.1.1.1 
Collection of Specimen(s) ................................................................................. 16 
9.1.1.2 
Handling of Specimen(s) ................................................................................... 16 
9.1.1.3 
Shipping of Specimen(s) (if multicenter) ......................................................... 16 
9.1.1.4 
Site(s) Performing Correlative Study (if multicenter) ...................................... 16 
9.2 
Special Studies .............................................................................................................. 16 
9.2.1 
Title – Special Correlative Study #1 ..................................................................... 16 
9.2.1.1 
Assessment ........................................................................................................ 16 
9.2.1.2 
Method of Assessment ...................................................................................... 16 
9.2.1.3 
Timing of Assessment ....................................................................................... 16 
10.  MEASUREMENT OF EFFECT ............................................................................................ 16 
10.1 Response Criteria ............................................................................................................ 16 
10.2 Duration of Response ..................................................................................................... 16 
10.3 Progression-Free Survival .............................................................................................. 17 
10.4 Other Response Parameters .......................................................................................... 17 
11. DATA REPORTING / REGULATORY CONSIDERATIONS ................................................ 17 
11.1 Data Collection ................................................................................................................. 17 
11.1.1 REDCap ..................................................................................................................... 17 
11.2 Regulatory Considerations ............................................................................................. 17 
11.2.1 Institutional Review Board/Ethics Committee Approval ....................................... 17 
11.2.2 Ethical Conduct of the Study ................................................................................... 18 
11.2.3 Informed Consent ..................................................................................................... 18 
11.2.4 Compliance with Trial Registration and Results Posting Requirements ............ 19 

Protocol # 20-07022437 
Version Date: 04/14/2023 
Page # iv 
11.2.5 Record Retention ...................................................................................................... 19 
12. STATISTICAL CONSIDERATIONS ..................................................................................... 19 
12.1 Study Design/Endpoints ................................................................................................. 19 
12.2 Sample Size/Accrual Rate ............................................................................................... 19 
12.3 Stratification Factors ....................................................................................................... 20 
12.4 Analysis of Endpoints ..................................................................................................... 20 
12.4.1 
Analysis of Primary Endpoints ......................................................................... 20 
12.4.2 
Analysis of Secondary Endpoints .................................................................... 20 
12.5 Interim Analysis ............................................................................................................... 20 
12.6 Reporting and Exclusions .............................................................................................. 20 
12.6.1 
Evaluation of Toxicity ........................................................................................ 20 
12.6.2 
Evaluation of Response ..................................................................................... 20 
13. ADVERSE EVENT REPORTING REQUIREMENTS ........................................................... 20 
13.1 Adverse Event Definition ................................................................................................ 20 
13.1.1 
Investigational Agent or Device Risks (Expected Adverse Events) .............. 21 
13.1.2 
Adverse Event Characteristics and Related Attributions ............................... 21 
13.1.3 
Recording of Adverse Events ........................................................................... 21 
13.1.4 
Reporting of AE to WCM IRB ............................................................................. 21 
13.1.5 
Reporting Events to Participants ...................................................................... 21 
13.1.6 
Events of Special Interest .................................................................................. 21 
13.1.7 
Reporting of Pregnancy ..................................................................................... 21 
13.2 Definition of SAE ............................................................................................................. 22 
13.2.1 
Reporting of SAE to IRB .................................................................................... 22 
13.2.2 
Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor-
Investigator] ......................................................................................................................... 22 
13.2.3 
Reporting of SAE to Eclipse Medical ................................................................ 22 
13.3 AE/SAE Follow Up ........................................................................................................... 23 
13.4 Time Period and Frequency for Event Assessment and Follow Up ........................... 23 
14. UNANTICIPATED PROBLEMS INVOLVING RISKS TO SUBJECTS OR OTHERS .......... 23 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others 
(UPIRTSO) ................................................................................................................................ 23 
14.1.2 
Unanticipated Problem Reporting .................................................................... 24 
15. DATA AND SAFETY MONITORING PLAN (DSMP) ........................................................... 24 
16. REFERENCES ..................................................................................................................... 26 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # v 
 
 
 
Statement of Compliance 
 
The trial will be carried out in accordance with International Conference on Harmonisation Good 
Clinical Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies 
(45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR 
Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are 
responsible for the conduct, management, or oversight of NIH-funded clinical trials have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials 
will be submitted to the Institutional Review Board (IRB) for review and approval.  
Approval of both the protocol and the consent form must be obtained before any 
participant is enrolled.  Any amendment to the protocol will require review and approval by 
the IRB before the changes are implemented to the study.  In addition, all changes to the 
consent form will be IRB-approved; a determination will be made regarding whether a new 
consent needs to be obtained from participants who provided consent, using a previously 
approved consent form. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # vi 
 
 
 
 
 
Confidentiality Statement 
 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or 
institutional review boards. The contents of this document shall not be disclosed to others without 
written authorization from WCM, unless disclosure on ClinicalTrials.gov is federally required. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # vii 
 
List of Abbreviations 
 
WCM 
PRP 
PPP 
PGIA 
PGA 
AE 
ADE 
SAE 
UADE 
NSI 
Weill Cornell Medicine 
Platelet-rich plasma  
Platelet-poor plasma 
Physician Global Improvement Score 
Physician Global Assessment 
Adverse events 
Adverse Device Effect 
Serious Adverse Event 
Unanticipated Adverse Device Effect 
Nail Superficial Abnormality Index 
 
 

Protocol #20-07022437 
Version Date: 01/15/2021 
 
  
Page # 1 
 
1. Protocol Summary 
 
Full Title: Use of Platelet-rich plasma (PRP) therapy in patients with Brittle Nail Syndrome 
Short Title: 
 
 
 
Platelet-rich Plasma for Brittle Nail Syndrome  
Clinical Phase: 
 
 
Phase 4 
Principal Investigator:  
Shari R. Lipner MD, PhD 
Study Description:   
Brittle nail syndrome is a common condition with no available 
effective treatments. The purpose of this study is to assess the 
efficacy and safety of platelet-rich plasma therapy for brittle nail 
syndrome. 8 of 10 fingernails per participant will be treated with 
platelet-rich plasma (PRP), while the remaining 2 fingernails will 
receive injections with platelet-poor plasma (PPP). Efficacy will be 
assessed at the end of the study by an independent blinded 
endpoint committee. 
 
Sample Size: 
 
N=10 participants.  
Enrollment: 
 
This study will enroll 10 subjects and screen up to 20.   
Study Population: 
 
Patients presenting with brittle nail syndrome to the Weill Cornell 
Medicine, Department of Dermatology, specialized nail clinic.  
Enrollment Period:  
1 year.  
Study Design: 
            This is a single center study with a PROBE design- Prospective 
Randomized Open Label Blinded Endpoint Design, i.e. Treatment 
is open label with respect to patient and investigators but is 
blinded to the endpoint committee. 10 patients presenting que 
signs and symptoms of brittle nail syndrome will be included. 8 of 
10 nails will be randomized to receive treatment with platelet-rich 
plasma, and 2 of 10 nails will receive injections with platelet-poor 
plasma (controls). Each patient will receive 3 treatments and high-
quality images will be taken. At the end of the study an 
independent blinded endpoint committee composed of 3 experts 
on nail diseases will assess efficacy using the Physician Global 
Improvement score. Adverse effects associated to treatment will 
be collected throughout the study.  
 
Description of Sites/  
Facilities Enrolling 
Participants:  
 
Weill Cornell Dermatology - 1305 York Avenue, NY, NY 10021 
Weill Cornell Dermatology - East Side, 425 E 61st St 4th floor, New York, NY 10065 
 
 
Study Duration: 
 
October 2022. 
Participant Duration: 
12 - 14 weeks. 
Study Agent/Device Name  

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 2 
 
Intervention Description: 
Platelet-rich plasma (PRP), injected into the proximal nail fold 
monthly for 3 months. It is defined as a device by the Food and 
Drug Administration (FDA), and it is a self-contained disposable kit 
containing two sterile blood separating vacuum tubes, two sleeve 
filters, various needles and a transferring device. 
 
Primary Objective: 
The primary objective of this study is to demonstrate the efficacy 
of platelet-rich plasma (PRP) injections for brittle nails.  
 
Secondary Objectives: 
The secondary objective of this study is to demonstrate the safety 
and tolerability of PRP injections for brittle nails. 
 
Primary Endpoints: 
The Primary efficacy endpoint will be the change in the Physician 
Global Improvement Assessment (PGIA) of the 8 target nails from 
baseline to weeks 12 - 14 of follow-up to determine efficacy of 
PRP injection in the treatment of brittle nail syndrome.   
 
Secondary Endpoints: 
Subject reported assessments of nail health will be analyzed using 
descriptive statistics. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 3 
 
1.1 
Schema 
 
Flow diagram 
 
Screening Visit 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screen potential participants by inclusion and exclusion criteria; obtain history, review of medications, document, take 
nail clipping sample for histopathology to tule out onychomycosis.  
 
Administer initial study intervention for participants that fulfill inclusion and exclusion criteria and have a negative 
histopathology result for onychomycosis. Patient instructions, take digital phonographs  
Review of eligibility criteria. Collection of adverse events. Collection of Patient Satisfaction Survey. Take digital photographs. 
Final Assessment by independent blinded 
endpoint committee. 
 
Arm 2 (controls) 
N fingernails: 2/10 per 
participant 
Arm 1(treatment) 
N fingernails: 8/10 per 
participant 
Randomize 
fingernails of patients that fulfil all inclusion criteria and have a negative 
histopathology result from the past 6 months  
Final 
Visit 4: 
Week 12 or 14 
Visit 2: 
Week 4 or 6 
Visit 1: Week 
0 or 2 
 
Administer thirst study intervention Review of eligibility criteria and collection of adverse events. Take digital photographs.  
 
Administer second study intervention. Review of eligibility criteria and collection of adverse events. Take digital photographs.  
Visit 3: 
Week 8 or 10 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 4 
 
1.2 
Study Objectives and End Points 
 
1.2.1  Primary Objectives  
 
The primary objective of this study is to demonstrate the efficacy of platelet-rich plasma 
(PRP) injections for brittle nails. 
 
1.2.2  Secondary Objectives  
 
The secondary objective of this study is to demonstrate the safety and tolerability of PRP 
injections for brittle nails. 
 
1.2.4 Primary Endpoints 
 
The Primary efficacy endpoint will be the change in the Physician Global Improvement 
Assessment (PGIA) of the 8 target nails from baseline to weeks 12 – 14 of follow up to 
determine efficacy of PRP injection in the treatment of brittle nail syndrome.   
 
1.2.5 Secondary Endpoints 
 
Subject reported assessments of nail health will be analyzed using descriptive statistics. 
 
2. Background 
 
2.1 Disease 
 
Brittle Nail Syndrome is a heterogeneous abnormality characterized by roughness of the surface 
of the nail plate, fragility or raggedness of the distal nail, splitting and peeling. It is most frequent 
in elderly individuals and affects about 20% of the population with women affected twice as 
frequently as men. Many patients view brittle nails as a cosmetic problem and a substantial 
number indicate that these nail abnormalities may be painful, may impair daily activities, and 
may have a negative impact on occupational abilities. Treatment is challenging for the clinician 
and is dependent upon cooperation of the patient. Treatment of brittle nails is aimed at 
restoration and maintenance of a normal degree of nail plate hydration by minimizing exposure 
to dehydrating chemicals and by use of moisturizers, such as alpha-hydroxy acids. There are 
currently no consistently effective treatments for this condition. 
 
2.2 Investigational Agent/Device, or Surgical Treatment/Method 
 
Platelet-rich plasma (PRP) is an autologous concentration of platelets, which can 
release quantities of growth factors and cytokines. As previously reported, such a 
complex of bioactive agents can promote the healing and restoration of multiple tissues 
when injured. PRP injections have been used to promote hair growth in dermatology and 
alleviation of joint instability in orthopedics. PRP injections into the nail matrix may 
promote the growth nails in patients with brittle nails and offer them better functionality. 
 
 
2.3 Rationale 
 
Nail Plate (NP) brittleness is a very common nail complaint, with up to 20% of the population 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 5 
 
experiencing some form of brittleness in their nails and is much more common for women over 
50[1]. Nail brittleness is characterized by nails that split, flake and crumble, become soft and 
lose elasticity. All the signs of Brittle Nail Syndrome can be present at once or only partially 
present. Brittle Nail syndrome itself does not cause any pain, however it can cause functional 
problems due to the inability to use the nail and cosmetic problems, which can distress the 
patient [2]. Pain can occur due to the splitting of the nail, and in some studies, it correlates to 
depression in patients [3]. The most common cause of brittle nails is idiopathic, and the 
mechanism is poorly understood, it may have to do with the water content in the nails [4], but 
there very few studies in the area. Inflammatory disease such as psoriasis, lichen planus, lichen 
stratus, alopecia areata, Darier’s disease and eczema can also cause secondary Brittle Nail 
syndrome. When Brittle Nail Syndrome is caused by an inflammatory disease, treatment of the 
underlying condition can help with Brittle Nail syndrome, however most patients have idiopathic 
Brittle Nail Syndrome and there is no effective treatment for the condition [5]. Biotin has been 
suggested as a treatment; however, it is poorly studied and the FDA issued an warning 
suggesting that biotin can cause interference with laboratory testing [6,9,10]. PRP injections 
have been used successful in other dermatological conditions such as androgenetic alopecia [7] 
and non-dermatological conditions like sports-related muscle, tendon and ligament injuries [8]. 
Platelet-rich plasma (PRP) is an autologous concentration of platelets, which can release 
quantities of growth factors and cytokines. As previously reported, such a complex of bioactive 
agents can promote the healing and restoration of multiple tissues when injured. PRP injection 
into the nail matrix may help promote growth of health nails in patients with idiopathic Brittle Nail 
syndrome by releasing growth factors and cytokines. 
References: 
1. 
Chen, P., et al., Intra-articular platelet-rich plasma injection for knee osteoarthritis: a 
summary of meta-analyses. J Orthop Surg Res, 2019. 14(1): p. 385. 
2. 
Chessa, M.A., et al., Pathogenesis, Clinical Signs and Treatment Recommendations in 
Brittle Nails: A Review. Dermatol Ther (Heidelb), 2019. 
3. 
Dicle, O., A. Bilgic Temel, and K.H. Gulkesen, Platelet-rich plasma injections in the 
treatment of male androgenetic alopecia: A randomized placebo-controlled crossover study. J 
Cosmet Dermatol, 2019. 
4. 
Gequelim, G.C., et al., Perception of brittle nails in dermatologic patients: a cross-
sectional study. An Bras Dermatol, 2013. 88(6): p. 1022-5. 
5. 
Kazakos, K., et al., The use of autologous PRP gel as an aid in the management of 
acute trauma wounds. Injury, 2009. 40(8): p. 801-5. 
6. 
Lubach, D., W. Cohrs, and R. Wurzinger, Incidence of brittle nails. Dermatologica, 1986. 
172(3): p. 144-7. 
7. 
Scher, R.K., Brittle nails. Int J Dermatol, 1989. 28(8): p. 515-6. 
8. 
van de Kerkhof, P.C., et al., Brittle nail syndrome: a pathogenesis-based approach with 
a proposed grading system. J Am Acad Dermatol, 2005. 53(4): p. 644-51. 
9. 
Lipner SR. Rethinking biotin therapy for hair, nail, and skin disorders. J Am Acad 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 6 
 
Dermatol. 2018 Jun;78(6):1236-1238. 
10. 
John JJ, Lipner SR. Consumer Perception of Biotin Supplementation. J Cutan Med Surg. 
2019 Nov/Dec;23(6):613-616 
 
2.4  Risk/Benefit Assessment  
 
 
2.4.1 Known Potential Risks 
 
PRP therapy has not been studied for nail disease in the past. Risks associated 
with the use of PRP therapy in the context of hair restoration and skin aging are 
mostly mild and transient. They include pain, erythema, bruising/ecchymosis, 
edema, tenderness, scarring, bleeding or infection at the injection site.  
 
2.4.2 Known Potential Benefits  
 
Platelet-rich plasma (PRP) is an autologous concentration of platelets, which can release 
quantities of growth factors and cytokines. Such a complex of bioactive agents can promote the 
healing and restoration of multiple tissues when injured. PRP injections have been used to 
promote hair growth in dermatology and alleviation of joint instability in orthopedics. PRP 
injections into the nail matrix may promote the growth nails in patients with brittle nails and offer 
them better functionality. 
 
2.4.3 Assessment of Potential Risks and Benefits 
 
There are currently no consistently effective treatments for brittle nail syndrome. Risks 
associated with platelet-rich plasma (PRP) therapy for hair restoration and skin aging have been 
shown to be mostly mild and transient. If PRP is shown to be effective for brittle nail syndrome 
in this study, patient’s quality of life and functionality may significantly improve.  
 
3. Study Design 
 
3.1 Overall Design 
 
This is a single center evaluation of 10 patients with signs and symptoms of brittle nails. 
Patients will be consented and 8/10 fingernails will be treated with PRP and 2/10 fingernails 
will be used as controls. Computer software will be used to randomly generate a 
randomization table for each participant. Randomization for each participant will be done on 
the same day of their first treatment, after all inclusion and exclusion criteria, including a 
negative histopathology report for onychomycosis are fulfilled. Blood will be drawn from a 
vein in the patient's arm into a 11 ml Eclipse PRP Tube. The blood is processed using a 
centrifuge machine from eclipse medical. After centrifugation, the platelet poor portion will be 
separated from the platelet-rich portion. The proximal nail folds are cleansed with alcohol. 
Using a 1ml syringe and 30g needle, 0.1-0.2 ml of platelet-rich plasma is injected into 8 
proximal nail folds (treated nails), while 2 proximal nail folds (untreated nails) are injected 
with platelet-poor plasma. The study patients will be treated with PRP injections monthly for 
3 months. Study patients may not have used any medications on the nails 3 months prior to 
the study or nail polish 1 month prior to the study. The patient must abstain from using any 
medication, moisturizers, oils, or nail polishes during the study period. The primary efficacy 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 7 
 
endpoint will be the individual physician observed Physician Global Improvement Score 
(PGIA), which encompasses observed improvement of lamellar splitting, transverse splitting, 
ridges and longitudinal grooves, longitudinal splitting, and nail thickness of target nails. This 
is a PROBE design- Prospective Randomized Open Label Blinded Endpoint Design, i.e. 
Treatment is open label with respect to patient and investigators but is blinded to the 
endpoint committee. High quality images will be obtained utilizing a Canon camera and 
reviewed by an independent blinded endpoint committee (3 dermatologists with expertise in 
nails disease Dr. Richard Scher, Dr. Matilde Iorizzo, and Dr. Bianca Maria Piraccini) for 
PGIA (Physician Global Improvement Assessment. If necessary due to poor image quality 
(e.g. light source not properly deployed), exposure correction post-imaging may be applied 
to images that are deemed unsatisfactory. The present study Is not funded, Eclipse Medical 
provided the required PRP kits, including the sterile tubes.  
 
PGA (Physician Global Assessment) Score:  
The Principal Investigator will utilize the Physician Global Assessment (PGA) score for 
screening purposes during the screening/baseline visit to determine eligibility. The PGA will 
be comprised of five components: lamellar splitting, transverse splitting, ridging and 
longitudinal groove, longitudinal splitting, and nail thickness. Lamellar splitting, which 
represents onychoschizia, is defined as distal furrows or splits encompassing the distal nail 
plate involving the complete free edge of the nail plate.  The second component, transverse 
splitting, is described as horizontal splitting from the free edge of the nail plate- with at least 
2 or 3 horizontal splits of the distal nail plate. The third component, ridging and longitudinal 
grooves, is defined by at least 50% of the nail plate showing deep ridges and corresponding 
grooves. The fourth component, longitudinal splitting, which represents onychorrhexis, is 
defined as at least one deep longitudinal split of the entire nail plate. The fifth component, 
nail thickness, is defined by a clearly visible change in nail thickness. The presence of each 
of these components during the screening/baseline visit will represent 1 point on a scale. 
The inclusion criterion requires patients to have a score of at least 2 out of a maximum of 5 
points.  
The components used in the PGA assessment have been based on the scoring system 
used by Van der Kerkhof et. Al in their study, “Brittle nail syndrome: A pathogenesis-based 
approach with a proposed grading system”. In this study, a grading system of 0-3 was used 
for each component, with 0-none, 1-mild, 2-moderate, 3-severe. The scale used for 
screening in the present study mirrors the moderate (score of 2) criteria used in the study by 
van der Kerkhof et. Al.  
 
The Nail Superficial Abnormality Index (NSI): 
The surface of the nails is divided into four quadrants, and each quadrant is scored for four 
parameters, namely, pitting, discoloration, longitudinal ridging and horizontal ridging. The 
presence or absence of any of these four parameters is scored as 1 or 0, respectively. Thus, 
the maximum possible score for a nail is 16 and minimum is 0. 
 
Adverse Events and Reporting  
Adverse events (AE) assessment will be ongoing throughout the study. All adverse events 
shall be reported by the clinical Investigator to the IRB as described below.  
  
Adverse Device Effect (ADE)  
Any sign, symptom, or disease in a study subject that occurs during the course of a clinical 
trial that is determined by the investigator to have a causal relationship or possible causal 
relationship with the device under investigation.  

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 8 
 
  
Serious Adverse Event (SAE)  
Any untoward medical occurrence in a subject, regardless of whether the event is related to 
the device that:  
 
a.  results in death;  
b.  results in a life-threatening illness or injury;  
c.   results in a permanent impairment of a body structure or body function;  
d.  requires in-subject hospitalization or prolongation of existing hospitalization  
e.  requires a medical or surgical intervention that was necessary to preclude permanent 
impairment of a body function, or prevent permanent damage to a body structure, either 
situation suspected to be due to the use of a medical product.  
f.   If exposed prior to conception or during pregnancy may have resulted in an adverse 
outcome in the child.  
g.  Does not fit the other outcomes, but the event may jeopardize the patient and may 
require medical or surgical intervention (treatment) to prevent one of the other outcomes. 
Examples include allergic bronchospasm (a serious problem with breathing) requiring 
treatment in an emergency room, serious blood dyscrasias (blood disorders) or 
seizures/convulsions that do not result in hospitalization. The development of drug 
dependence or drug abuse would also be examples of important medical events.  
  
Serious adverse events (SAEs) and unanticipated adverse device effects (UADEs) must be 
reported within 24 hours of knowledge of the event to the IRB.  
  
Unanticipated Adverse Device Effect (UADE) Any serious adverse effect on health and 
safety or any life-threatening problem or death caused by, or associated with a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application, or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects.  
  
The Investigator shall be responsible for determination of the causal relationship of all 
adverse events to the device and/or procedure. The Principal Investigator is responsible for 
monitoring the safety of the subjects enrolled.  
  
Any serious adverse events will be reviewed and analysed by the Principal Investigator as 
soon as the event occurs and will be documented in the subject’s binder.  
  
INVESTIGATIONAL DEVICE SUPPLY  
 PRP (medical device) will be supplied by Eclipse Medical. 
 
3.2 Scientific Rationale for Study Design 
 
This is a PROBE design- Prospective Randomized Open Label Blinded Endpoint Design, i.e. 
Treatment     is open label with respect to patient and investigators but is blinded to the endpoint 
committee. 8/10 Fingernails per participant will be randomized to receive treatment with platelet-
rich plasma and the remaining 2 nails will receive injections with platelet-poor plasma. Potential 
problems with the control group include nonuniform results due to the lack of response for the 2 
nails receiving injections with platelet-poor plasma.  
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 9 
 
3.3 Justification for Dose  
 
The nail matrix, located at the proximal nail fold, functions as the nail growth center. We 
hypothesize that injecting 0.1-0.2 ml of platelet-rich plasma in this area will promote nail 
growth. On the other hand, injecting platelet-poor plasma, which lacks bioactive agents 
compared with the platelet-rich section, should not promote nail growth.  
 
3.4 End of Study Definition 
 
A participant is considered to have completed the study if he or she has completed all 
phases of the study including the last visit. The end of the study is defined as completion of 
the last visit or procedure. 
 
4. Subject Selection 
 
4.1 Study Population 
 
Subjects with a diagnosis of brittle nail syndrome in all 10 fingernails who meet the inclusion 
and exclusion criteria will be eligible for participation in this study.   
 
4.2 Inclusion Criteria 
 
1. Patients who have been diagnosed with brittle nails  
2. Must understand and voluntarily sign an informed consent form  
3. Must be male or female and aged 18-95 years at time of consent  
4. Must be able to adhere to the study visit schedule and other protocol requirements  
5. A nail clipping with histopathology that is negative for the presence of dermatophyte 
infection  
6. Patient must present with at least a score of 2 on the PGA scale. 
4.3 Exclusion Criteria   
1. Inability of the patient to provide written informed consent for any reason.  
2. Subject has psoriasis, lichen planus, dermatophyte infection or other confounding 
abnormalities that are severe enough to result in a clinically abnormal fingernail  
3. Use of any medication within 90 days prior to start of study 
4. Inability to abstain for nail polishes, nail gels during the study period  
5. Subject is pregnant or planning pregnancy. 
 
4.4 Lifestyle Considerations 
 
During this study, participants are asked to: 
• 
Abstain from using any medication, moisturizers, oils, or nail polishes during the study 
period. Participants that do not fulfill this criterion will be excluded from the study.  
 
4.5 Screen Failures  
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 10 
 
Screen failures are defined as participants who consent to participate in the clinical trial but 
are not subsequently randomly assigned to the study intervention or entered in the study. A 
minimal set of screen failure information is required to ensure transparent reporting of 
screen failure participants, to meet the Consolidated Standards of Reporting Trials 
(CONSORT) publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because 
of a <specify modifiable factor> may be rescreened. Rescreened participants should be 
assigned the same participant number as for the initial screening. 
 
4.6 Strategies for Recruitment and Retention 
 
 
Patients attending Weil Cornell Medicine, Department of Dermatology, specialized nail clinic run 
by PI Dr. Shari Lipner, with signs and symptoms of brittle nail syndrome will be targeted. 10 
participants will be included in the study and approximately 20 patients will be screened. All 
participants will be enrolled in one of two U.S. locations:  
Weill Cornell Dermatology - 1305 York Avenue, NY, NY 10021 
In the present study, participants will not be compensated or provided any incentives.  
 
5. Registration Procedures 
 
5.1 Subject Registration (WCM only) 
 
Subjects will be registered within the WRG-CT as per the standard operating procedure 
for Subject Registration.  
 
6. Study Procedures 
 
6.1 Schedule of Assessments 
Table 1. Schedule of trial event 
   
Screeni
ng visit 
Visit 1: 
Wk 0 
or 2 
Visit 2: 
Wk 4 or 
6 
 Visit 3: 
Wk 8 or 
10 
Visit 4: 
Wk 12 or 
14 
Off Studyd 
 
Agent Administration  
 
 
 
X 
 
X 
 
X 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical exam 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Concurrent medications 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 11 
 
 
 
 
 
 
6.1.1 Screening Visit (visit 1) 
 
Screening visit 
 
During the screening visit, all inclusion and exclusion criteria will be reviewed. Obtaining patient 
consent, history and review of medications will take place. A nail clipping will be obtained for 
those patients that have not had a negative histopathology result for onychomycosis within the 
past 6 months. If the patient has had a previous nail clipping within the past 6 months, that will 
suffice. Therefore, for some patients Visit 1 can take place on the same day of the Screening 
Visit, while for others Visit 1 will take place on week 2 (after a negative histopathology result for 
onychomycosis is received). 
 
 
 
 
6.1.2 Treatment Phase  
 
The 10 fingernails of each participant will be randomly assigned to treatment with 
platelet-rich plasma or platelet-poor plasma (placebo) treatment groups in a 8:2 
ratio using a computer-generated randomization scheme developed by the data 
manager.   
 
 
Study Visits  
Visit 1: Week 0 - 2 
  
Subjects who fulfill all inclusion and exclusion criteria, and sign informed consent are eligible 
to enroll and begin Visit 1 procedures that same day. For those patients that do not have a 
negative histopathology result for onychomycosis within the past 6 months, a nail clipping is 
obtained during screening visit and visit 1 procedure will take place in week 2 assuming the 
patient fulfill all inclusion and exclusion criteria.  
  
Visit 1 Procedures:  
 
• 
Patient Instructions  
• 
Take High resolution digital photographs  
• 
Randomization of participants that fulfilled all inclusion and exclusion criteria 
• 
First Injection of PRP 
 
Visits 2 and 3: Week 4 - 6 (±7 days) and Week 8 - 10 (± 7 days)  
The following procedures will be performed on these visits:  
• 
Second and third injections of PRP 
Obtain 
nail 
clipping 
sample 
 
X 
 
 
 
 
 
 
 
 
 
 
Adverse 
event 
evaluation 
 
 
 
X 
 
X 
 
X 
 
X 
 
 
 
Digital photographs 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Patient 
satisfaction 
survey 
 
 
 
 
 
 
 
 
 
X 
 
 
Efficacy assessment 
 
 
 
 
 
 
X 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 12 
 
• 
Review of eligibility criteria including review of concomitant medications/cosmetics  
• 
Collection of adverse events  
• 
Take High resolution digital photographs 
 
Visit 4: Week 12 – 14 (± 7 days)  
Collection of adverse events  
 
•    Take High resolution digital photographs 
• 
Collection of Patient Satisfaction Survey  
 
 
6.1.3 Follow-up Phase 
 
After visit 4 (week 12 - 14) is completed, the independent blinded endpoint committee will judge 
improvement of brittle nail syndrome based on high quality digital photography taken throughout 
the study. 
7. Study Intervention 
 
 
7.1 Study Intervention/Device Description   
 
Platelet-rich plasma kit it is defined as a device by the Food and Drug Administration 
(FDA).  
 
7.2 Availability 
 
Platelet-rich plasma kit and centrifuge machine is an investigational device supplied to 
investigators by Eclipse Medical. 
 
7.3 Acquisition and Accountability  
 
 
 
Agent Inventory Records/Device Logs – The investigator, or a responsible party 
designated by the investigator, will maintain a careful record of the inventory and 
disposition of all agents/device received from Eclipse Medical on a Drug Accountability 
Record Form (DARF) or Device Log.  
 
7.4 Formulation, Appearance, Packaging, and Labeling  
 
Platelet-rich plasma kit is a self-contained disposable kit containing two sterile blood 
separating vacuum tubes, two sleeve filters, various needles and a transferring device. 
 
 
7.5 Product Storage and Stability 
 
Sterile tubes and centrifuge machine should be stored in temperature between 41°F – 100°F. 
PRP should be applied to the same patient from whom the blood was drawn.  
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 13 
 
 
7.6 Preparation 
 
Blood will be drawn from a vein in the patient's arm into a 11 ml Eclipse PRP Tube. The 
blood is processed using a centrifuge machine from eclipse medical. After centrifugation, 
the platelet poor portion will be separated from the platelet-rich portion.  
 
7.7 Dosing and Administration 
 
The proximal nail folds are cleansed with alcohol. Using a 1ml syringe and 30g needle, 
0.1-0.2 ml of platelet-rich plasma is injected into 8 proximal nail folds (treated nails), 
while 2 proximal nail folds (untreated nails) are injected with platelet-poor plasma. The 
same volume will be administered during each study visit.  
 
 
7.7.1 Dosing Delays/Dose Modifications 
 
Table 2. 
AGENT(S) 
DOSE 
ROUTE 
VISIT 
PRP, PPP 
0.1-0.2 ml 
Intramatricial 
1 
PRP, PPP 
0.1-0.2 ml 
Intramatricial 
2 
PRP, PPP 
0.1-0.2 ml 
Intramatricial 
3 
 
 
7.8 General Concomitant Medication and Supportive Care Guidelines 
 
All concomitant medications will be recorded and/or updated on subject medication chart 
throughout the course of the study and saved in subject binder, if applicable. 
 
7.9 Duration of Therapy and Criteria for Removal from Study  
 
In the absence of treatment delays due to adverse event(s), treatment may continue for 
3 cycles or until one of the following criteria applies: 
 
• 
Intercurrent illness that prevents further administration of treatment, 
• 
Unacceptable adverse event(s), 
• 
Subject decides to withdraw from the study, or 
• 
General or specific changes in the subject’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator. 
  
Study Termination Guidelines: A subject’s follow-up in the study will end after one of the 
following applies: 
• 
Subject’s voluntary withdrawal 
• 
Subject lost to follow-up 
• 
Subject death 
• 
Completion of all scheduled study follow-up appointments 
• 
Any other rules specific to your study 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 14 
 
 
7.10 Duration of Follow Up 
 
Subjects will be followed 4 weeks after their last treatment. Subjects removed from study 
for unacceptable adverse events will be followed until resolution or stabilization of the 
adverse event. 
 
 
7.11 Measures to Minimize Bias: Randomization and Blinding  
 
Computer software will be used to randomly generate a randomization table. 8/10 fingernails will 
be randomly allocated to treatment with PRP and the remaining 2 fingernails will receive 
injections with PPP. Randomization for each participant will be done on the same day of their 
first treatment, after all inclusion and exclusion criteria, including a negative histopathology 
report for onychomycosis are fulfilled. For the present study, treatment will be open label with 
respect to patient and investigators but is blinded to the endpoint committee. High quality 
images will be obtained utilizing a Canon camera and reviewed by an independent blinded 
endpoint committee (3 dermatologists with expertise in nails disease Dr. Richard Scher, Dr. 
Matilde Iorizzo, and Dr. Bianca Maria Piraccini) for PGIA (Physician Global Improvement 
Assessment. 
 
7.12 Study Intervention/Follow-up Compliance 
 
During the baseline visit (standard of care visit), participants will be asked to schedule 
their follow-up study visits. In addition, patients will receive a call prior to their scheduled 
visit in order to confirm attendance.  
 
8. Study Intervention Discontinuation and Participant Discontinuation/Withdrawal 
 
Participants may withdraw voluntarily from the study or the PI may discontinue a 
participant from the study. Participants will be excluded if they have/develop psoriasis, 
lichen planus, dermatophyte infection or other confounding abnormalities that are severe 
enough to result in a clinically abnormal fingernail. Have used any medication within 90 
days prior to the start of the study. Use of nail polishes or gels during the study period. 
The subject gets pregnant or is planning pregnancy.  
 
8.1 Discontinuation of Study Intervention 
 
Discontinuation from PRP does not mean discontinuation from the study, and remaining 
study procedures should be completed as indicated by the study protocol. If a clinically 
significant finding is identified (including, but not limited to changes from baseline) after 
enrollment, the investigator or qualified designee will determine if any change in 
participant management is needed. Any new clinically relevant finding will be reported as 
an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the 
following: 
• 
Reason(s) for discontinuation, take digital photographs, assessment of concomitant 
medications.   
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 15 
 
8.2 Participant Discontinuation/Withdrawal from the Study 
 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following 
reasons: 
 
• 
Pregnancy 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition 
or situation occurs such that continued participation in the study would not be in the 
best interest of the participant 
• 
If the participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation 
• 
Participant unable to receive PRP.  
• 
Participant lost to follow-up after several attempts to contact subject to schedule 
study visit. 
The reason for participant discontinuation or withdrawal from the study will be recorded 
on the Case Report Form (CRF). Subjects who sign the informed consent form and are 
randomized but do not receive the study intervention may be replaced.  Subjects who 
sign the informed consent form, and are randomized and receive the study intervention, 
and subsequently withdraw, or are withdrawn or discontinued from the study, will be 
replaced. 
8.3 Lost to Follow Up 
A participant will be considered lost to follow-up if he or she fails to return for one or 
more scheduled visits and is unable to be contacted by the study site staff.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit up to 7 
days after the 4 weeks from the previous visit and counsel the participant on the 
importance of maintaining the assigned visit schedule and ascertain if the participant 
wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and if possible, 1 email). These contact attempts should be documented in the 
participant’s medical record or study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up. 
 
9. Correlative/Special Studies  
Not applicable  
 
9.1 Laboratory Correlative Studies 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 16 
 
9.1.1 Title – Laboratory Correlative Study #1 
 
9.1.1.1 Collection of Specimen(s) 
 
9.1.1.2 Handling of Specimen(s) 
 
9.1.1.3 Shipping of Specimen(s) (if multicenter) 
 
9.1.1.4 Site(s) Performing Correlative Study (if multicenter) 
 
9.2 Special Studies 
 
9.2.1 Title – Special Correlative Study #1 
 
9.2.1.1 Assessment 
 
9.2.1.2 Method of Assessment 
 
9.2.1.3 Timing of Assessment 
 
10.  Measurement of Effect 
 
PGA (Physician Global Assessment) Score:  
The Principal Investigator will utilize the Physician Global Assessment (PGA) score for 
screening purposes during the screening/baseline visit to determine eligibility. The PGA will 
be comprised of five components: lamellar splitting, transverse splitting, ridging and 
longitudinal groove, longitudinal splitting, and nail thickness. Lamellar splitting, which 
represents onychoschizia, is defined as distal furrows or splits encompassing the distal nail 
plate involving the complete free edge of the nail plate.  The second component, transverse 
splitting, is described as horizontal splitting from the free edge of the nail plate- with at least 
2 or 3 horizontal splits of the distal nail plate. The third component, ridging and longitudinal 
grooves, is defined by at least 50% of the nail plate showing deep ridges and corresponding 
grooves. The fourth component, longitudinal splitting, which represents onychorrhexis, is 
defined as at least one deep longitudinal split of the entire nail plate. The fifth component, 
nail thickness, is defined by a clearly visible change in nail thickness. The presence of each 
of these components during the screening/baseline visit will represent 1 point on a scale. 
The inclusion criterion requires patients to have a score of at least 2 out of a maximum of 5 
points. An independent blinded endpoint committee will assess change from baseline based 
on the PGA.  
 
10.1 Response Criteria 
 
 
Change in the PGA from baseline.  
 
10.2 Duration of Response  
 
Duration of overall response:  The duration of overall response is measured from the 
time measurement criteria are met for CR or PR (whichever is first recorded) until the 
first date that recurrent or progressive disease is objectively documented (taking as 
reference for progressive disease the smallest measurements recorded since the 
treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are first met 
for CR until the first date that recurrent disease is objectively documented. 
 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 17 
 
Duration of stable disease:  Stable disease is measured from the start of the treatment 
until the criteria for progression are met, taking as reference the smallest measurements 
recorded since the treatment started.  
 
10.3 Progression-Free Survival  
 
Not Applicable. 
 
10.4 Other Response Parameters 
 
Please see section 12.5 Secondary Endpoints. 
 
 
11. Data Reporting / Regulatory Considerations 
 
11.1 Data Collection 
 
 
The data collection plan for this study is to utilize REDCap to capture all treatment, 
toxicity, efficacy, and adverse event data for all enrolled subjects.  
 
11.1.1 REDCap 
 
REDCap (Research Electronic Data Capture) is a free data management 
software system that is fully supported by the Weill-Cornell Medical Center 
CTSC.  It is a tool for the creation of customized, secure data management 
systems that include Web-based data-entry forms, reporting tools, and a full 
array of security features including user and group-based privileges, 
authentication using institution LDAP system, with a full audit trail of data 
manipulation and export procedures.  REDCap is maintained on CTSC-owned 
servers that are backed up nightly and support encrypted (SSL-based) 
connections.  Nationally, the software is developed, enhanced and supported 
through a multi-institutional consortium led by the Vanderbilt University CTSA. 
 
11.2 Regulatory Considerations 
 
11.2.1 Institutional Review Board/Ethics Committee Approval  
 
As required by local regulations, the Investigator will ensure all legal aspects are covered, 
and approval of the appropriate regulatory bodies obtained, before study initiation.  
Before initiation of the study at each study center, the protocol, the ICF, other written 
material given to the patients, and any other relevant study documentation will be 
submitted to the appropriate Ethics Committee. Written approval of the study and all 
relevant study information must be obtained before the study center can be initiated or the 
IP is released to the Investigator. Any necessary extensions or renewals of IRB approval 
must be obtained for changes to the study, such as amendments to the protocol, the ICF, 
or other study documentation. The written approval of the IRB together with the approved 
ICF must be filed in the study files.  

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 18 
 
The Investigator will report promptly to the IRB any new information that may adversely 
affect the safety of the patients or the conduct of the study. The Investigator will submit 
written summaries of the study status to the IRB as required. On completion of the study, 
the IRB will be notified that the study has ended.  
 
All agreed protocol amendments will be clearly recorded on a protocol amendment form 
and will be signed and dated by the original protocol approving signatories. All protocol 
amendments will be submitted to the relevant institutional IRB for approval before 
implementation, as required by local regulations. The only exception will be when the 
amendment is necessary to eliminate an immediate hazard to the trial participants. In this 
case, the necessary action will be taken first, with the relevant protocol amendment 
following shortly thereafter.  
Once protocol amendments or consent form modifications are implemented at the lead 
site, Weill Cornell Medicine, updated documents will be provided to participating sites, as 
applicable. Weill Cornell Medicine must approve all consent form changes prior to local 
IRB submission.  
Relevant study documentation will be submitted to the regulatory authorities of the 
participating countries, according to local/national requirements, for review and approval 
before the beginning of the study. On completion of the study, the regulatory authorities 
will be notified that the study has ended.  
 
11.2.2 Ethical Conduct of the Study  
The Investigators and all parties involved should conduct this study in adherence to the 
ethical principles based on the Declaration of Helsinki, GCP, ICH guidelines and the 
applicable national and local laws and regulatory requirements.  
 
This study will be conducted under a protocol reviewed and approved by the applicable 
ethics committees and investigations will be undertaken by scientifically and medically 
qualified persons, where the benefits of the study are in proportion to the risks. 
 
11.2.3 Informed Consent 
 
The investigator or qualified designee must obtain documented consent according to ICH-
GCP and local regulations, as applicable, from each potential subject or each subject’s 
legally authorized representative prior to participating in the research study. Subjects who 
agree to participate will sign the approved informed consent form and will be provided a 
copy of the signed document.   
 
The initial ICF, any subsequent revised written ICF and any written information provided 
to the subject must approved by IRB prior to use. The ICF will adhere to IRB requirements, 
applicable laws and regulations. 
 
11.2.4 Compliance with Trial Registration and Results Posting Requirements  
 
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the 
Food and Drug Administration Amendments Act (FDAAA), the Sponsor-Investigator of the 
trial is solely responsible for determining whether the trial and its results are subject to the 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 19 
 
requirements for submission to http://www.clinicaltrials.gov. Information posted will allow 
subjects to identify potentially appropriate trials for their disease conditions and pursue 
participation by calling a central contact number for further information on appropriate trial 
locations and trial site contact information. 
 
11.2.5 Record Retention 
 
Essential documents are those documents that individually and collectively permit 
evaluation of the study and quality of the data produced.  After completion of the study, all 
documents and data relating to the study will be kept in an orderly manner by the 
Investigator in a secure study file.  Essential documents should be retained for 2 years 
after the final marketing approval in an ICH region or for at least 2 years since the 
discontinuation of clinical development of the IP. In addition, all subjects medical records 
and other source documentation will be kept for the maximum time permitted by the 
hospital, institution, or medical practice.   
 
12. Statistical Considerations 
 
12.1 Study Design/Endpoints 
 
For study design, please see section 3. Study Design. 
 
Endpoints  
The Primary efficacy endpoint will be the Physician Global Improvement Assessment (PGIA), 
which will be compared between follow-up point (week 12 - 14) and baseline point for nails with 
PRP injection, and between follow-up point (week 12 - 14) and baseline point for nails without 
PRP injection. The power analysis estimated that with approximately 44 nails with PRP injection 
enrolled in the study, a score change of 0.5 from baseline to week 12 – 14 can be detected 
through paired two-sided t-test with 90% power at 0.05 significant level for PRP group. The 
calculation assumed a standard deviation of 1 in scores. PGA is a novel tool that there is not 
enough reference to assume an accurate standard deviation, so the sample size estimation was 
also performed on a range of sd assumption. With assumption of sd in range of 0.5 to 1, 13 to 
97 nails would be needed for the PRP injection group to detect a score change of 0.5 from 
baseline to week 12 - 14 through paired two-sided t-test with 90% power at 0.05 significant 
level. 
Sample size estimation summary given different settings of standard deviation and meaningful 
changes 
 
sd=0.5 sd=1 sd=1.5 
Difference = 1 
5 
13 
26 
Difference = 0.5 
13 
44 
97 
 
Secondary  
 
Subject reported assessments of nail health will be analyzed using descriptive statistics. 
 
12.2 Sample Size/Accrual Rate 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 20 
 
 
With a total of 10 participants, 80 fingernails will be included in the treatment group, and 20 
fingernails in the control group.  
 
12.3 Stratification Factors  
 
Not applicable. 
 
 12.4 Analysis of Endpoints 
 
12.4.1 Analysis of Primary Endpoints 
 
Please see section 12.1 Study design/Endpoints 
 
12.4.2 Analysis of Secondary Endpoints 
 
Please see section 12.1 Study design/Endpoints 
 
12.5 Interim Analysis 
 
Not applicable.  
 
 12.6 Reporting and Exclusions 
 
12.6.1 Evaluation of Toxicity 
 
All subjects will be evaluable for toxicity from the time of their first treatment with PRP 
and PPP.  
 
12.6.2 Evaluation of Response 
 
All subjects included in the study will be assessed for response to treatment if they have 
received at least 3 treatments.  
 
13. Adverse Event Reporting Requirements  
 
Adverse event (AE) monitoring and reporting is a routine part of every clinical trial.  The 
investigator will be required to provide appropriate information concerning any findings that 
suggest significant hazards, contraindications, side effects, or precautions pertinent to the safe 
use of the drug or device under investigation.  Safety will be monitored by evaluation of adverse 
events reported by subjects or observed by investigators or research staff, as well as by other 
investigations such as clinical laboratory tests, x-rays, electrocardiographs, etc. 
 
13.1 Adverse Event Definition 
 
An adverse event (also referred to as an adverse experience) can be any unfavorable 
and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a drug, and does not imply any judgment about 
causality. An adverse event can arise with any use of the drug (e.g., off-label use, use in 
combination with another drug) and with any route of administration, formulation, or 
dose, including an overdose.  

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 21 
 
 
 
13.1.1 Investigational Agent or Device Risks (Expected Adverse Events) 
 
PRP has not been studied for nail diseases in the past. Adverse events associated with the use of PRP 
therapy in the context of hair restoration and skin aging are mostly mild and transient. They include 
pain, erythema, bruising/ecchymosis, edema, tenderness, scarring, bleeding and infection at the 
injection site. 
 
13.1.2 Adverse Event Characteristics and Related Attributions 
 
CTCAE term (AE description) and grade:  The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting.  A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site (http://ctep.cancer.gov). 
 
• 
Attribution of the AE: 
- Definite – The AE is clearly related to the study treatment. 
- Probable – The AE is likely related to the study treatment. 
- Possible – The AE may be related to the study treatment. 
- Unlikely – The AE is doubtfully related to the study treatment. 
- Unrelated – The AE is clearly NOT related to the study treatment. 
 
 
 
13.1.3 Recording of Adverse Events 
 
All adverse events will be recorded on a subject specific AE log. The AE log will be 
maintained by the research staff and kept in the subject’s research chart.    
 
 
13.1.4 Reporting of AE to WCM IRB 
 
All AEs occurring on this study will be reported to the IRB according to the IRB policy, 
which can be accessed via the following link:  
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting
_Policy.pdf.  
 
13.1.5 Reporting Events to Participants 
 
Not applicable.  
 
13.1.6 Events of Special Interest 
Any other confounding disease found in the histopathology analysis of the nail clipping during 
the screening phase will be communicated to the subject.  
 
13.1.7 Reporting of Pregnancy 
 
Discontinuation of study intervention, while continuing safety follow-up, requesting 
permission to follow pregnant women to pregnancy outcome.  
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 22 
 
13.2 Definition of SAE 
 
SAEs include death, life threatening adverse experiences, hospitalization or 
prolongation of hospitalization, disability or incapacitation, overdose, congenital 
anomalies and any other serious events that may jeopardize the subject or require 
medical or surgical intervention to prevent one of the outcomes listed in this 
definition.  
 
13.2.1 Reporting of SAE to IRB 
 
All SAEs occurring on this study will be reported to the IRB according to the IRB policy, 
which can be accessed via the following link:   
http://researchintegrity.weill.cornell.edu/forms_and_policies/forms/Immediate_Reporting
_Policy.pdf.  
 
13.2.2 Reporting of SAE to FDA [For Protocols Where WCMC is the Sponsor-
Investigator] 
 
IND application sponsor must report any suspected adverse reaction or adverse 
reaction to study treatment that is both serious and unexpected. Unexpected fatal 
or life-threatening suspected adverse reactions represent especially important 
safety information and must be reported to FDA as soon as possible but no later 
than 7 calendar days following the sponsor’s initial receipt of the information. 
i. death, 
ii. a life-threatening adverse event,   
iii. in-patient hospitalization or prolongation of existing hospitalization, 
iv. a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions, or   
v. a congenital anomaly or birth defect 
 
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 patient or research subject and may 
require medical or surgical intervention to prevent one of the outcomes listed as 
serious 
 
CDER-only Biologic INDs:  
Food and Drug Administration  
Center for Drug Evaluation and Research  
Therapeutic Biologic Products Document Room  
5901-B Ammendale Road  
Beltsville, MD 20705-1266  
 
13.2.3 Reporting of SAE to Eclipse Medical 
 
Institution will send Eclipse Medical copies of any and all serious adverse event 
reports filed with the FDA or other applicable regulatory authorities, as well as 
copies of any correspondence with the FDA or other applicable regulatory 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 23 
 
authorities, regarding any and all serious adverse events, irrespective of 
association with the Study Drug(s) in the course of the Clinical Trial, within 30  
business days of such report or correspondence being sent to the FDA or other 
applicable regulatory authorities.  Copies should be faxed directly to Eclipse 
Medical at (866)-558-0415.  
 
 
13.3 AE/SAE Follow Up 
 
All SAEs and AEs reported during this study will be followed until resolution or until the 
investigator confirms that the AE/SAE has stabilized and no more follow-up is required. 
This requirement indicates that follow-up may be required for some events after the 
subject discontinues participation from the study.  
 
13.4 Time Period and Frequency for Event Assessment and Follow Up 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to 
the attention of study personnel during study visits and interviews of a study participant 
presenting for medical care, or upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be 
captured on the appropriate case report form (CRF). Information to be collected includes 
event description, time of onset, clinician’s assessment of severity, relationship to study 
product (assessed only by those with the training and authority to make a diagnosis), 
and time of resolution/stabilization of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship. All AEs will be followed to 
adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s 
condition deteriorates at any time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. AEs characterized as 
intermittent require documentation of onset and duration of each episode. 
 
 
Jose Ricardo will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the 
last day of study participation.  At each study visit, the investigator will inquire about the 
occurrence of AE/SAEs since the last visit.  Events will be followed for outcome 
information until resolution or stabilization. 
 
 
14. Unanticipated Problems Involving Risks to Subjects or Others 
 
14.1 Definition of Unanticipated Problems Involving Risks to Subjects or Others 
(UPIRTSO) 
 
This definition could include an unanticipated adverse device effect, any serious adverse 
effect on health or safety or any life-threatening problem or death caused by, or associated 
with, a device, if that effect, problem, or death was not previously identified in nature, 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 24 
 
severity, or degree of incidence in the investigational plan or application (including a 
supplementary plan or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects (21 CFR 812.3(s)). 
 
14.1.2 Unanticipated Problem Reporting 
 
An investigator shall submit to the sponsor and to the reviewing Institutional Review 
Board (IRB) a report of any unanticipated adverse device effect occurring during an 
investigation as soon as possible, but in no event later than 10 working days after the 
investigator first learns of the effect (21 CFR 812.150(a)(1)), A sponsor who conducts an 
evaluation of an unanticipated adverse device effect under 812.46(b) shall report the 
results of such evaluation to the Food and Drug Administration (FDA) and to all 
reviewing IRB's and participating investigators within 10 working days after the sponsor 
first receives notice of the effect. Thereafter the sponsor shall submit such additional 
reports concerning the effect as FDA requests (21 CFR 812.150(b)(1)).    
 
15. Data and Safety Monitoring Plan (DSMP) 
 
In this section, please include a written plan of the measures that will be taken to ensure the safety 
of clinical research subjects and protect the validity and integrity of research data. The following 
questions should be addressed as a part of the DSMP and must be incorporated into your WCM 
eIRB application: 
 
• Include a description of the proposed monitoring entity (i.e. WCM DSMB, Independent 
Medical Monitor) and rationale for choosing the specified monitoring entity. If you are 
using an independent medical monitor or study monitoring committee/group, please 
specify their qualifications.  
• Describe the data/events that will be captured and submitted to the monitoring entity. 
Specify what data will be collected during the course of the study to assess both safety 
and efficacy.  
• Describe what adverse events may cause the subject to terminate protocol treatment. 
Specifically, describe treatment stopping rules for an individual subject. 
• How will adverse events and unanticipated problems be reported to the monitoring 
entity and with what frequency? 
• How often will the monitoring entity review data/events (i.e. annually, semi-annually, 
etc.)?  
• Describe the complete study stopping rules (criteria for study suspension and potential 
study termination) statistical considerations. If there are no defined stopping rules, 
please provide a rationale. Also, state any specific triggers for action.  
• All dose escalation trials are required to define dose limiting toxicities, rules for 
escalation of dose, and criteria for stopping the trial and defining the Maximum 
Tolerated Dose. 
• How will the monitoring entity’s comments/review be disseminated? (e.g. Submitted to 
the IRB at the time of continuing review and submitted to participating sites upon receipt 
of review comments.)  
 
 
 
 
 

Protocol # 20-07022437 
Version Date: 04/14/2023 
 
 
Page # 25 
 
16. References 
 
1. 
Chen, P., et al., Intra-articular platelet-rich plasma injection for knee osteoarthritis: a 
summary of meta-analyses. J Orthop Surg Res, 2019. 14(1): p. 385. 
2. 
Chessa, M.A., et al., Pathogenesis, Clinical Signs and Treatment Recommendations in 
Brittle Nails: A Review. Dermatol Ther (Heidelb), 2019. 
3. 
Dicle, O., A. Bilgic Temel, and K.H. Gulkesen, Platelet-rich plasma injections in the 
treatment of male androgenetic alopecia: A randomized placebo-controlled crossover study. J 
Cosmet Dermatol, 2019. 
4. 
Gequelim, G.C., et al., Perception of brittle nails in dermatologic patients: a cross-
sectional study. An Bras Dermatol, 2013. 88(6): p. 1022-5. 
5. 
Kazakos, K., et al., The use of autologous PRP gel as an aid in the management of 
acute trauma wounds. Injury, 2009. 40(8): p. 801-5. 
6. 
Lubach, D., W. Cohrs, and R. Wurzinger, Incidence of brittle nails. Dermatologica, 1986. 
172(3): p. 144-7. 
7. 
Scher, R.K., Brittle nails. Int J Dermatol, 1989. 28(8): p. 515-6. 
8. 
van de Kerkhof, P.C., et al., Brittle nail syndrome: a pathogenesis-based approach with 
a proposed grading system. J Am Acad Dermatol, 2005. 53(4): p. 644-51. 
9. 
Lipner SR. Rethinking biotin therapy for hair, nail, and skin disorders. J Am Acad 
Dermatol. 2018 Jun;78(6):1236-1238. 
10. 
John JJ, Lipner SR. Consumer Perception of Biotin Supplementation. J Cutan Med Surg. 
2019 Nov/Dec;23(6):613-616