Clinical trial NCT05261386
Conditions: Meibomian Gland Dysfunction
Sponsor: Cloudbreak Therapeutics, LLC
Start date: 2022-03-04; Completion date: 2023-03-29
Enrollment: 95 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Study Design

Structure: Multicenter, randomized, double-masked, vehicle-controlled, parallel group study Duration: 1 month of TID treatment Treatment Groups, Dosing, and Treatment Regimen Study Treatment: CBT-008 topical ophthalmic solution Control Treatment: CBT-008 vehicle

Detailed description:
Structure Multicenter, randomized, double-masked, vehicle-controlled, parallel group study.

Duration Stage 1: 1 month Stage 2: 1 day (1 dose)

Treatment Groups, Dosing, and Treatment Regimen

1. Study Treatment Stage 1: CBT-008 ophthalmic solution was administered as 1 drop OU TID Stage 2: CBT-008 ophthalmic solution was administered as 1 drop in the study eye
2. Control Treatment CBT-008 vehicle
3. Methods for Masking Study medication will be packaged in identical kits and will be labeled with medication kit numbers. The central randomization system will provide the site with a specific medication kit number for the patient corresponding to the treatment group assigned.
4. Instructions for Storage, Use, and Administration Study medication will be supplied as preservative free-unit dose containers, where 1 mL of CBT-008 ophthalmic solution will be aseptically filled into 3 mL Low Density Polyethylene (LDPE) ophthalmic dropper bottles. Study medication should be stored at room temperature in a secure area at clinical sites and dispensed only to patients enrolled into the clinical study. Patients will be instructed to store study medication in a cool place at room temperature at home. Study medication will be administered TID, one drop, to both eyes. First instillation of study medication on the first day will be applied by subject or care provider with site staff's observation for training and supervision. During the rest of the study treatment, patients will self-administer the medication TID for 1 month.

Arms: arm 1: Vehicle arm 2: lower concentration dose arm 3: higher concentration dose
Interventions: intervention 1: CBT-008
Intervention descriptions: intervention 1: Treat MGD

Protocol documents:
Prot_SAP_ICF_000.pdf: 
CBT-008 
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CLOUDBREAK THERAPEUTICS 
 
Protocol-short 
 
A Phase 2 multicenter, double-masked, randomized, vehicle-controlled, parallel study 
to evaluate the safety, efficacy and pharmacokinetics of CBT-008 ophthalmic solution in 
patients with Meibomian Gland Dysfunction associated Dry Eye Disease (MGD-DED) 
 
Protocol Number:   
 
 
 
 
 
 
CBT-CS105 
ClinicalTrials.gov Identifier  
 
 
 
 
NCT05261386 
Name of Investigational Product:   
 
 
CBT-008 Ophthalmic Solution 
Governing IRB/IEC:  
 
 
 
 
 
 
Sterling IRB 
Sponsor:   
 
 
 
 
 
 
 
 
 
ADS Therapeutics, LLC 
15615 Alton Parkway, Suite 450 
Irvine, CA 92618, USA 
Emergency Phone Numbers:   
 
 
 
1-949-678-9752 
SAE Reporting Fax Number:   
 
 
 
1-949-271-6302 
SAE Reporting Email Address:  
 
 
 
leng_bing@cloudbreaktherapeutics.com 
Medical Safety Monitor Contact:   
 
 
Ken Sall, M.D. 
Tel (office): 1-562-754-2947 
Email: drsall@sallresearch.com 
 
 
 
 
Date:  
 
 
 
 
 
 
 
 
 
 
March 29, 2023 


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Study Number: CBT-CS105 
Name of Sponsor:  ADS Therapeutics Inc 
Name of Finished Product: Ophthalmic Solution of CBT-008  
Name of Active Ingredient: CBT-008 
Title of Study: A Phase 2 multicenter, double-masked, randomized, vehicle-controlled, parallel study to 
evaluate the safety, efficacy and pharmacokinetics of CBT-008 ophthalmic solution in patients with 
Meibomian Gland Dysfunction associated Dry Eye Disease (MGD-DED) 
Study Period:  
Study Initiation Date (First Subject Enrolled): 04 March 2022 
Study Completion Date (Last Subject Completed): 07 September 2022 
Phase of Development: Phase 2 
Objectives:   
The study objective for Stage 1 was to evaluate the safety and efficacy of CBT-008 topical ophthalmic 
solution for treating meibomian gland dysfunction−associated dry eye disease (MGD-DED). 
 
The study objective for Stage 2 was to determine the pharmacokinetics (PK) profile of CBT-008 topical 
ophthalmic solution after a single topical ocular dose in meibomian gland dysfunction (MGD) or 
healthy patients. 
Methodology:   
This was a multicenter, randomized, double-masked, vehicle-controlled, parallel-group study with a 
4-week treatment period (Stage 1). The co-primary endpoints were measured at Week 4. Stage 2 used a 
2-day, single-center, randomized, open-label design to assess PK. Patients from a single center who 
completed Stage 1 participated in Stage 2 (unless more patients were needed, in which case healthy 


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volunteers could be enrolled). 
 
Stage 1: Randomized comparison of CBT-008 (2 concentrations) vs CBT-008 vehicle 
In Stage 1, patients were randomized in a 1:1:1 treatment allocation to receive CBT-008 2.5%, CBT-008 
10%, or CBT-008 vehicle, with no stratification by site or by baseline signs and/orsymptoms. One drop of 
study drug was self-administered in both eyes (OU) 3 times daily (TID) for 1 month, starting at the Day 1 
Visit, with additional visits at Weeks 1, 2, and 4. Efficacy was assessedby co-primary endpoints – change 
from baseline at Week 4 in ocular discomfort score (ODS) and in cornea staining grade using the National 
Eye Institute (NEI) scale of 0 to 3. Additional efficacy variables were change in ocular discomfort as 
assessed with a visual analog scale (VAS), change in BLepharitIS Symptom (BLISS) score, change in 
meibum quality score (MQS), change in eyelid margin vascularity grade (EMVG), change in tear break-
up time (TBUT), and change in Schirmer I Test score. Safety was assessed by adverse events (AEs), best-
corrected visual acuity (BCVA), intraocular pressure (IOP), slit lamp biomicroscopy, dilated 
ophthalmoscopy, vital signs, urine pregnancy test (for women of childbearing potential), and laboratory 
assessments. 
 
Stage 2: Pharmacokinetic analysis of CBT-008 
Following at least a 1-month waiting period after completion of Stage 1, patients from a single site 
enrolled in an optional PK substudy (healthy volunteers could have been used if not enough patients were 
enrolled). Patients were dosed by site staff to receive 1 drop of CBT-008 2.5% or CBT-008 10% 
in the study eye only. Blood was collected from these patients at pre-dose and at the following postdose 
time points: 15 ± 3 min, 30 ± 5 min, 1 hr ± 10 min, 2 hr ± 10 min, 4 hr ± 15 min, and 8 hr ± 30 min. 
 
Number of Subjects:  
Stage 1 
Planned: Approximately 90 patients 
Analyzed: 95 patients 
Stage 2 
Planned: Sixteen patients 
Analyzed: 19 patients 
Diagnosis and Main Criteria for Eligibility: 
Major Inclusion Criteria 
Stage 1 inclusion criteria 
 
Diagnosed with MGD in both eyes and meet the following: 
a. 
ODS ≥ 2  
b. VAS score between 35-90% for at least 1 of the 7 categories 
c. 
Total Cornea staining grade ≥ 3  
d. Total meibum quality score (MQS) between 6-17 from the sum of the 6 lower eyelid 
central glands in at least one lower eyelid  
e. 
FTBUT ≤ 5 s  
f. 
Schirmer I Test (anaesthetized) ≥ 5 mm after 5 minutes in study eye 


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g. BCVA LogMAR ≥ +0.7 in each eye. 
 
 
Subject continues to qualify at visit 2 despite the ability and willingness to apply eyelid hygiene 
as instructed.  Willing to withhold the use of artificial tears and eye lubricants during the treatment 
phase. 
 
≥ 18 years old 
 
Able to provide written informed consent and comply with study assessments for the full duration 
of the study. 
Stage 2 inclusion criteria 
1. Patients who completed the Stage 1 Exit Visit for at least 1 month or healthy volunteers 
2. At least 18 years of age at time of consent and able to provide written informed consent 
 
Major Exclusion Criteria 
Stage 1 exclusion criteria 
 
Uncontrolled systemic disease in the opinion of the Investigator 
 
Active allergy, infection, or ocular surface inflammatory disease unrelated to MGD 
 
History of ocular herpes disease in either eye 
 
Ocular surgery history within 6 months  
 
Patients taking eye lubricants must stop after Day 1 visit 
 
Use of topical treatment of the eye/eyelid with antibiotics, NSAIDS, or vasoconstrictors to treat 
MGD or DED within 14 days of screening; steroids, cyclosporin A or lifitegrast within 28 days 
of screening 
 
Current or anticipated use of other topical ophthalmic medications. Patients must have 
discontinued use of ophthalmic medications for at least 2 weeks prior to the screening visit, the 
use of artificial tears is allowed. 
 
Anticipated wearing of contact lenses during any portion of the study. Patients, who wear soft 
contact lenses should discontinue wearing them at least 3 days prior to screening visit. Patients 
wearing rigid gas permeable or hard contact lenses should discontinue wearing them at least 3 
weeks prior to screening visit 
 
Active rosacea involving the eyelids within 60 days of Screening 
 
Current enrollment in an investigational drug or device study or participation in such a study 
within 30 days prior to entry into this study 
 
Any condition or situation which may put the patient at significant risk, may confound the study 
results, or may interfere significantly with the patient’s participation in the study 
 
Female who are pregnant or nursing or planning a pregnancy during the study 
Stage 2 exclusion criteria 
1. Females who were pregnant or nursing 
2. Current enrollment in an investigational drug or device study or participation in such a study 
within 30 days prior to entry into this study 
3. Previously randomized in the CBT-CS102 clinical trial and dosed with CBT-006 


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Test Product, Dose and Mode of Administration, Batch Number:  
Stage 1: CBT-008 ophthalmic solution (2.5% or 10%) was administered as 1 drop OU TID 
Stage 2: CBT-008 ophthalmic solution (2.5% or 10%) was administered as 1 drop in the study eye 
Reference Therapy, Dose and Mode of Administration, Batch Number: Not applicable. 
Duration of Treatment:  
Stage 1: 1 month 
Stage 2: 1 day (1 dose) 
Study Measurements:  
 
Stage 1 efficacy: 
• ODS (co-primary endpoint at Week 4) 
• Cornea staining grade (co-primary endpoint at Week 4) 
• Ocular discomfort using the VAS 
• BLISS 
• MQS 
• EMVG 
• TBUT 
• Schirmer I Test score 
Stage 1 safety: 
• BCVA 
• IOP 
• Slit lamp biomicroscopy 
• Dilated ophthalmoscopy 
• Vital signs 
• Urine pregnancy test 
• Urinalysis 
• Hematology and blood chemistry 
• AEs 
Stage 2 pharmacokinetics: 
• Peak concentration at Tmax (Cmax), time of peak concentration (Tmax), and, if applicable, area 
under the curve from time 0 to 8 hours post-dose (AUC0-8hr) and terminal half-life (t1/2)  
 
Statistical Methods:  
 
Stage 1 statistical methods: 
Continuous (quantitative) variable summaries included the number of patients (n) with non-missing 
values, mean, standard deviation (SD), median, minimum, and maximum. Categorical (qualitative) 


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variable summaries included the frequency and percentage of patients who were in the particular 
category of each possible value. 
Unless otherwise indicated, all statistical tests were conducted at the 0.05 significance level using 
2-tailed tests, and P values were reported. Corresponding 95% confidence intervals were presented for 
statistical tests, if applicable. 
The analyses and documentation described in this Statistical Analysis Plan (SAP) were for the final 
analysis of the study. All statistical analyses were programmed using SAS® software version 9.4 (SAS 
Institute, Cary, NC, USA). 
Due to the exploratory nature of this study, the planned sample size was determined empirically. To 
account for premature discontinuation, 90 patients were planned to be enrolled, with the expectation 
that at least 75 patients (25 per treatment group) would complete the study. It was anticipated that this 
sample size would be adequate to identify trends in the data. 
Stage 2 statistical methods: 
Prior to database lock, a detailed SAP was approved. Descriptive statistics (mean, SD, etc.) were 
calculated for plasma CBT-008 concentrations for each treatment group. If applicable, plasma PK 
parameters were calculated. Parameters included Cmax, Tmax, and, if applicable, AUC0-8hr and t1/2. 
Duration of Study Follow-Up: None 
 


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Stage 1 Schedule of Events 
Study Procedures 
Visit 1 
Screening 
Day -14±2
Visit 2 
Day 1a 
 
Visit 3 
Week 2 
(± 3 days)
Visit 4 
Week 4 
(± 5 days)
Informed 
Consent/Authorization 
X 
 
 
 
Subject ID Assignment 
X 
 
 
 
Demographics 
X 
 
 
 
Medical / Ocular History 
X 
 
 
 
Concomitant 
Medications/Concurrent 
Procedures 
X 
X 
X 
X 
Vital Sign measurements 
(blood pressure, heart rate, 
body temperature) 
X 
X 
X 
X 
Pregnancy test, if applicable 
X 
X 
X 
X 
Blood chemistry & 
hematology 
X 
 
 
X 
VAS assessment  
X 
X 
X 
X 
ODS assessment 
X 
X 
X 
X 
BLISS assessment 
X 
X 
X 
X 
Best-Corrected Visual Acuity
X 
X 
 
X 
Intraocular Pressure 
X 
X 
 
X 
Biomicroscopy 
X 
X 
X 
X 
Slit-lamp assessment 
including MQS and lid 
margin grading 
X 
X 
X 
X 
TBUT 
X 
X 
X 
X 
Cornea staining grading 
X 
X 
X 
X 
Schirmer I test 
(anaesthetized, last to 
perform prior to 
ophthalmoscopy) 
X 
X 
X 
X 
Ophthalmoscopy (dilated) 
X 
 
 
X 
Query for Serious Medical 
Events/Adverse Events 
X 
X 
X 
X 
Randomization 
 
X 
 
 
Inclusion/Exclusion Criteria 
X 
X 
 
 
Study Medication 
 
Dispense Dispense+ 
Collect 
Collect 
Exit 
 
 
 
X 
a 
All measurements at baseline Day 1 are prior to the instillation of first dose. 
 


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Stage 2 Schedule of Events 
 
Study Period  
Visit 1 – 
Screening 
(Day -7 ± 
4) 
Visit 2 – Day 1 (time after dosing in hour) 
Time Points
Anytime
Pre-dose
H: 0
H: 0.25
H: 0.5
H: 1.0
H: 2.0
H: 4.0
H: 8.0
Inform Consent Form
X
Medical History
X
X
Demographics
X
Pregnancy Test
X
Serious Medical 
Events
X 
X 
 
 
 
 
 
 
 
Dosing
X
Blood PK Sampling
X
X
X
X
X
X
X
Exit
X