Clinical trial NCT04475432
Conditions: Blepharitis
Keywords: Demodex
Sponsor: Tarsus Pharmaceuticals, Inc.
Start date: 2020-09-09; Completion date: 2021-05-04
Enrollment: 421 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare the safety and efficacy of TP-03, 0.25%, an eyedrop, to its vehicle control for the treatment of blepharitis due to Demodex, a microscopic mite frequently found in human hair follicles. The hypothesis for the study is the proportion of participants cured at Day 43 with treatment by TP-03, 0.25%, is greater than the proportion cured by treatment with its vehicle.

Detailed description:
This Phase 2b/3 study is a randomized, controlled, multicenter, double-masked, parallel trial to compare the safety and efficacy of TP-03, 0.25%, to vehicle control for the treatment of Demodex blepharitis. The primary objective of the study is to assess the safety and efficacy of TP-03 compared to its vehicle from Day 1 to Day 43 in adult participants with mild to severe Demodex blepharitis. The primary efficacy endpoint will be cure based upon collarettes. Safety will be determined by assessing adverse effects related to the treatment as well as evaluating any changes in visual acuity, intraocular pressure, slit lamp biomicroscopy and dilated ophthalmoscopy findings.

Arms: arm 1: TP-03, lotilaner ophthalmic solution, 0.25%, administered topically twice a day for approximately 43 days arm 2: Vehicle of TP-03 ophthalmic solution, administered topically twice a day for approximately 43 days
Interventions: intervention 1: TP-03, 0.25% intervention 2: TP-03 Vehicle
Intervention descriptions: intervention 1: TP-03, lotilaner ophthalmic solution, 0.25%, administered twice a day intervention 2: Vehicle of TP-03 ophthalmic solution, administered twice a day

Protocol documents:
Prot_002.pdf: 
Randomized, Controlled, Multicenter, Double-Masked, 
Parallel, Phase 2b/3 Trial to Evaluate the Safety and 
Efficacy of TP-03 for the Treatment of Demodex 
Blepharitis (Saturn-1)  
Protocol Number: TRS-009 
IND Sponsor: Tarsus Pharmaceuticals, Inc. 
Funded by: Tarsus Pharmaceuticals, Inc. 
 
25-Jan-2021
            NCT04475432


Saturn-1 Trial 
 
Protocol TRS-009 
 
  
 
1 
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, and 21 CFR Part 312)  
 
Investigators and clinical trial site staff who are responsible for the conduct, management, or oversight 
of 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. 
 
1 
 
PROTOCOL SUMMARY 
  
1.1 
SYNOPSIS  
Title: 
Randomized, Controlled, Multicenter, Double-Masked, Parallel, Phase 
2b/3 Trial to Evaluate the Safety and Efficacy of TP-03 for the Treatment 
of Demodex Blepharitis (Saturn-1) 
  
Study Description and 
Hypotheses: 
This Phase 2b/3 study is a randomized, controlled, multicenter, double-
masked, parallel trial to compare the safety and efficacy of TP-03 to 
vehicle control for the treatment of Demodex blepharitis.  The 
hypothesis for the study is the proportion of participants cured at Day 43 
with treatment by TP-03, lotilaner ophthalmic solution, 0.25%, is greater 
than the proportion cured by treatment with vehicle.    
  
Test Article: 
TP-03, lotilaner ophthalmic solution, 0.25% 
 
Control Article: 
Vehicle of TP-03 
 
Study Design: 
Prospective, randomized, double-masked, multicenter, two-arm, parallel 
vehicle-controlled study 
 
Objective: 
To demonstrate the safety and efficacy of TP-03, 0.25%, for the 
treatment of Demodex blepharitis 
 
Endpoints: 
Primary Endpoint:  Proportion of participants cured based on their 
collarette score of the upper eyelid of the analysis eye at Day 43. 


Saturn-1 Trial 
 
Protocol TRS-009 
 
  
 
2 
 
Secondary Endpoints:   
• 
Proportion of participants with their Demodex mites eradicated in 
the analysis eye at Day 43. 
• 
Proportion of participants cured based on a composite of collarette 
and erythema scores of the upper eyelid of the analysis eye at Day 
43. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety will be determined by assessing adverse effects related to the 
active treatment as well as evaluating any changes in visual acuity, 
intraocular pressure, slit lamp biomicroscopy and dilated 
ophthalmoscopy findings.  
 
 
 
 
Phase: 
2b/3 
 
Number of Participants: 
 
Up to 418 participants 
 
 
 
Study Population: 
Participants with blepharitis due to Demodex infestation defined as 
having an elevated mite density, collarettes and erythema 
 
Description of Sites: 
 
   
Description of Study 
Treatment: 
Participants eligible to be randomized will receive one of the following 
treatments administered bilaterally BID for 43 days:  TP-03, 0.25%, or 
the TP-03 vehicle ophthalmic solution.   
  
Study Duration: 
 
 
Participant Duration: 
The study duration for an individual participant is estimated to be 
approximately  weeks for participants enrolled in 
 and 
 
weeks for participants enrolled in 
 
 







SAP_003.pdf: 
STATISTICAL ANALYSIS PLAN 
Randomized, Controlled, Multicenter, Double-Masked, 
Parallel, Phase 2b/3 Trial to Evaluate the Safety and 
Efficacy of TP-03 for the Treatment of Demodex 
Blepharitis (Saturn-1)
Sponsor:  
Tarsus Pharmaceuticals, Inc. 
Protocol Number: 
TRS-009 
  
 
 
 
Date:  
26MAY2021 
 
 
NCT04475432


Protocol TRS-009 SAP
 
26MAY2021 
Confidential & Proprietary 
Page 3 of 38 
 
Table of Contents 
1. 
Introduction............................................................................................................................... 6 
2. 
Study Objectives ...................................................................................................................... 6 
2.1 Primary Endpoint ...................................................................................................................... 6 
2.2 Secondary Endpoints ............................................................................................................... 6 
 
2.4 Safety and Other Assessments................................................................................................ 7 
2.5 Statistical Hypotheses .............................................................................................................. 7 
3. 
Study Design and Procedures ................................................................................................. 8 
3.1 General Study Design .............................................................................................................. 8 
3.2 Schedule of Visits and Assessments ....................................................................................... 9 
4. 
Study Treatments ................................................................................................................... 12 
4.1 Method of Assigning Subjects to Treatment Groups ............................................................. 12 
4.2 Masking and Unmasking ........................................................................................................ 12 
5. 
Sample Size and Power Considerations ................................................................................ 13 
6. 
Data Preparation .................................................................................................................... 13 
6.1 Input Data ............................................................................................................................... 13 
6.2 Output Data ............................................................................................................................ 14 
7. 
Analysis Populations .............................................................................................................. 15 
7.1 Full Analysis Set ..................................................................................................................... 15 
7.2 COVID-19 Analysis Set .......................................................................................................... 15 
7.3 Per-Protocol Set ..................................................................................................................... 15 
7.4 Safety Set ............................................................................................................................... 15 
8. 
General Statistical Considerations ......................................................................................... 15 
8.1 Unit of Analysis....................................................................................................................... 15 
8.2 Missing or Inconclusive Data Handling .................................................................................. 16 
8.3 Definition of Baseline ............................................................................................................. 17 
8.4 Data Analysis Conventions .................................................................................................... 17 
8.5 Adjustments for Multiplicity ..................................................................................................... 17 
9. 
Disposition of Subjects ........................................................................................................... 18 
10. 
Demographic and Pretreatment Variables ............................................................................. 19 
10.1 Demographic Variables .......................................................................................................... 19 
11. 
Medical History and Concomitant Medications ...................................................................... 19 
11.1 Medical History ....................................................................................................................... 19 
11.2 Concomitant Medications ....................................................................................................... 19 
11.3 Concomitant Procedures ........................................................................................................ 20 
12. 
Dosing Compliance and Treatment Exposure ....................................................................... 20 


Protocol TRS-009 SAP
 
26MAY2021 
Confidential & Proprietary 
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12.1 Dosing Compliance ................................................................................................................ 20 
12.2 Treatment Exposure ................................................................. Error! Bookmark not defined. 
13. 
Efficacy Analyses ................................................................................................................... 20 
13.1 Primary Analysis .................................................................................................................... 22 
13.1.1 
Sensitivity Analyses.................................................................................................... 22 
13.1.1.1 
Sensitivity Analysis I ........................................................................................... 23 
13.1.1.2 
Sensitivity Analysis II .......................................................................................... 23 
13.1.1.3 
Sensitivity Analysis III ......................................................................................... 23 
13.1.1.4 
Sensitivity Analysis IV ........................................................................................ 23 
13.1.1.5 
Sensitivity Analysis V ......................................................................................... 23 
13.2 Secondary Analyses .............................................................................................................. 24 
13.2.1 
First Secondary Efficacy Endpoint ............................................................................. 24 
13.2.2 
Second Secondary Efficacy Endpoint ........................................................................ 24 
 
14. 
Safety Analyses ..................................................................................................................... 25 
14.1 Adverse Events ...................................................................................................................... 25 
14.2 Corrected Distance Visual Acuity ........................................................................................... 28 
14.3 Slit-Lamp Biomicroscopy Examination ................................................................................... 28 
14.4 Dilated Fundus Examination .................................................................................................. 29 
 
14.6 Intraocular Pressure ............................................................................................................... 29 
 
14.8 Urine Pregnancy Test ............................................................................................................ 30 
 
 
 
14.11 
Corneal Staining ............................................................................................................. 30 
15. 
Interim Analyses ..................................................................................................................... 31 
16. 
Changes from Protocol-Stated Analyses ............................................................................... 31 
 
 
 
 
 
 
 
 
 
 
 


Protocol TRS-009 SAP
 
26MAY2021 
Confidential & Proprietary 
Page 5 of 38 
List of Abbreviations 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ATC 
Anatomical Therapeutic Chemical 
BID 
Bis in die (Two Times a Day) 
CDVA 
Corrected Distance Visual Acuity 
CI 
Confidence Interval 
COVID-19 
Coronavirus Disease 2019 
CS 
Clinically Significant 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IOP 
Intraocular Pressure 
IRB 
Institutional Review Board 
logMAR 
Logarithm of the Minimum Angle of Resolution 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
NCS 
Not Clinically Significant 
PDF 
Portable Document Format 
PP 
Per Protocol 
PT 
Preferred Term 
RDC 
Remote Data Capture 
RTF 
Rich Text Format 
SaaS 
Software-as-a-Service 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SDC 
Statistics & Data Corporation 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment-Emergent Adverse Event 
WHODrug 
World Health Organization Drug Dictionary 
WOCBP 
Women of Childbearing Potential 
 
 


Protocol TRS-009 SAP
 
26MAY2021 
Confidential & Proprietary 
Page 6 of 38 
1. 
Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and reporting for 
protocol TRS-009, version 3.0 dated 25JAN2021. 
This SAP is being written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, efficacy, and safety 
assessments that will be evaluated. This SAP provides details of the specific statistical methods that will 
be used. The statistical analysis methods presented in this document will supersede the statistical analysis 
methods described in the clinical protocol. If additional analyses are required to supplement the planned 
analyses described in this SAP, they may be completed and will be identified in the clinical study report. 
2. 
Study Objectives 
The objective of this study is to demonstrate the safety and efficacy of lotilaner ophthalmic solution(TP-03), 
0.25% compared to its vehicle as a cure of mild to severe Demodex blepharitis. 
The secondary objectives of this study are: 
• 
To demonstrate the efficacy of TP-03, 0.25%, to eradicate Demodex mites from the eyelid margin; 
and  
• 
To demonstrate the efficacy of TP-03, 0.25%, to eliminate collarettes and erythema from the eyelid 
margin. 
 
 
  
2.1 
Primary Endpoint  
The primary efficacy endpoint is the proportion of subjects cured based on their collarette score of 0 at Day 
43 of the upper eyelid of the analysis eye. The primary safety endpoint is assessment of treatment-related 
adverse effects.  
2.2 
Secondary Endpoints 
The secondary efficacy endpoints include the following: 
• 
Proportion of subjects with their Demodex mites eradicated, mite density of 0 at Day 43 in the 
analysis eye 
• 
Proportion of subjects cured based on a composite of collarette score (0) and erythema cure/score 
(0) of the upper eyelid of the analysis eye at Day 43 








Protocol TRS-009 SAP
 
26MAY2021 
Confidential & Proprietary 
Page 10 of 38 
Table 2. Schedule of Visits and Assessments