Conditions: Pterygium
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 75
Healthy volunteers: no

Brief summary:
Stage 1: Single Ascending Dose, Safety, Tolerability and Pharmacokinetics (n=24)

Stage 2: Multiple Dose, Safety and Efficacy Study with 28-day Dosing and 5 months Followup (n=51)

Detailed description:
Stage 1: Single Ascending Dose, Safety, Tolerability and Pharmacokinetics (n=24)

Objectives are to evaluate ocular safety and tolerability by biomicroscopy, ophthalmoscopy, intraocular pressure and visual acuity, and to assess general safety by physical exams, vital signs, clinical laboratory tests and adverse events reporting and to evaluate systemic CBT-001 exposure by Cmax, Tmax and an estimation of the area under the curve (AUC).

Three dose cohorts will be planned with a dose ascending strategy to guide dose concentrations (n=8 per Cohort x 3 cohorts = 24). Primary pterygium patients will be selected in this phase because the main goal is to assess the safety and tolerability of CBT-001 and primary pterygium patients are much easier to recruit. The \~8 primary pterygium patients from each Cohort will be administered a single ocular drug dose at Day 1 in the eye with primary pterygium; the unaffected eye will be dosed with vehicle. Examinations will be performed at both screening day (Day 0) and Day 1. Blood samples at pre-dose, 0.25, 0.5, 1, 2, 4 and 8 hours post dose will be taken at Day 1 to assess systemic pharmacokinetics (PK). The data will be reviewed by Data Review Committee (DRC) to determine whether to initiate enrollment for the next Cohort.

Cohort 1 will begin at the lowest CBT-001 concentration of 0.02%, followed by an increasing dose to 0.05% for Cohort 2 and then to 0.2% for Cohort 3. If no safety issues are found at all doses, the highest dose of 0.2% will be used for the next phase study.

Stage 2: Multiple Dose, Safety and Efficacy Study with 28-day Dosing and 5 months Followup (n=51)

Objectives are to evaluate ocular and systemic safety of CBT-001 in primary or recurrent patients that have moderate to severe pterygium vascularity and to assess whether CBT-001 is efficacious in reducing pterygium vascularity and pterygium lesion growth. The dosing will be 4 weeks. The followup period will be 5 months.

Study Population Characteristics: Approximately 50 (30 primary pterygium and 20 recurrent) patients will be enrolled at up to 3 centers to have an estimated 40 patients complete the study based on an anticipated dropout rate of 20%. Although we have no evidence to suggest attrition due to Adverse Effects (AEs), the dropout rate is most conservative based on industry experience in comparable clinical studies. Patients will be randomized in a 1:1 treatment allocation to receive either CBT-001 0.2% or Vehicle.

Dosage/Dose regimen: One drop of the assigned study medication will be administered in the study eye TID for 4 weeks. The study eye is defined as the qualified eye (i.e., the eye meeting the inclusion criterion for primary or recurrent pterygium). If both eyes are qualified, then the eye with the more severe vascularity grade on the Pterygium Hyperemia Grading Scale at the baseline (Day 1) visit will be the study eye. If both eyes meet the criterion and have the same severity, the right eye will be the study eye. Patients with bilateral pterygium will administer study medication only in the study eye. The fellow eyes in all study subjects will be untreated.

Arms:
arm 1: One drop in the study administered one time only for one day arm 2: One drop in the study administered three times daily (TID) for 4 weeks arm 3: One drop in the study administered three times daily (TID) for 4 weeks

Interventions: intervention 1: CBT-001 single dose intervention 2: Vehicle intervention 3: CBT-001 Multi-dose
Intervention descriptions: intervention 1: One drop in the study administered one time intervention 2: One drop in the study administered three times daily (TID) for 4 weeks intervention 3: One drop in the study administered three times daily (TID) for 4 weeks

Protocol document:
Prot_SAP_000.pdf: 
CLOUDBREAK THERAPEUTICS  
Protocol-short 
A Phase 2a Multicenter, Randomized, Vehicle-Controlled, Dose Escalating Study to 
Evaluate the Safety, Efficacy and Pharmacokinetics of CBT-001 Ophthalmic Solution in 
Patients with Primary or Recurrent Pterygium 
 
Protocol Number: 
 
 
 
CBT-CS101 
ClinicalTrials.gov Identifier 
 
NCT03049852 
 
Name of Investigational Product:   
CBT-001 Ophthalmic Solution  
Governing IRB/IEC: 
 
 
Sterling IRB 
Sponsor: 
 
 
 
 
Cloudbreak 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: 
 
ni_jinsong@cloudbreaktherapeutics.com 
Medical Safety Monitor Contact:  
Robert David, M.D. 
 
 
 
 
 
 
Tel (office): 1-949-200-7899 
 
 
 
 
 
 
Tel (mobile): 1-949-246-8368 
 
 
 
 
 
 
Email: robert.david@clindevop.com 
Date:   
 
 
 
 
April 12, 2017 
 


 
 
Study Number: CBT-CS101 
Name of Sponsor:  
Cloudbreak Therapeutics, LLC 
15615 Alton Parkway, Suite 450 
Irvine, CA 92618 
Tel: 1-949-678-9752 
Email: ni_jinsong@cloudbreaktherapeutics.com 
Contact Person: Jinsong Ni, Ph.D. 
Name of Finished Product: Ophthalmic Solution of CBT-001 
Name of Active Ingredient: CBT-001 
Title of Study: A Phase 2a multicenter, randomized, vehicle-controlled, dose escalating study to evaluate the 
safety, efficacy and pharmacokinetics of CBT-001 ophthalmic solution in patients with primary or recurrent 
pterygium 
Study Period:  
Study Initiation Date (First Subject Enrolled): May, 2017 
Study Completion Date (Last Subject Completed): December, 
2017 
 
Phase of Development: Phase 2a Stage 2 
Objectives:  
To evaluate the safety, tolerability and effect in patients with primary pterygium or pterygium recurrence via 
unilateral topical ocular dosing of CBT-001 ophthalmic solution for 28 days with 5 months follow-up observation  
Methodology:  
Strategy:  
• 
Evaluate ocular and systemic safety profile of CBT-001 ophthalmic solution in patients with primary or 
recurrent pterygium, that are associated with moderate to severe pterygium vascularity; 
• 
Establish whether CBT-001 is efficacious in reducing pterygium vascularity; 
• 
Assess whether CBT-001 is efficacious in inhibiting pterygium lesion growth; 
Plan:  
A multicenter, double-masked, vehicle-controlled and parallel study is designed with 28 days TID repeat ocular 
dosing of vehicle and the highest tolerable dose (e.g., 0.2%), followed by 5-month post dose observation. 
Ophthalmic and physical examinations will be performed at screening, Day 1 and weeks 2, 4, 8, 16, and 24. External 
photograph of the pterygium eye will be taken using a digital camera and the lesion length, width and area as well 
as pterygium vascularity will be measured or graded from these images at an independent image reading center.  
Number of Subjects: 50 patients with primary or recurrent pterygium. 
Diagnosis and Main Criteria for Eligibility: 
Major Inclusion Criteria 
• 
Primary pterygium with 0.6-3.5 mm lesion length from the anterior edge of limbus to the central cornea, 
associated with pterygium vascularity ≥ Grade 3 using the 5-point Pterygium Hyperemia Grading Scale 


a. 
A minimum of Grade 3 (moderate) pterygium vascularity in the study eye at the screening (day 
-60 to day -7) and baseline (day 1) visits, using the 5-point Pterygium Hyperemia Grading 
Scale (0 = absent, 1 = trace, 2 = mild, 3 = moderate, 4 = severe); 
b. About 0.6-3.5 mm of encroachment of the pterygium onto the cornea of the study eye at the 
screening (day -60 to day -7) and baseline (day 1) visits as measured by slit lamp examination 
(investigator assessment). The measurement is as described by Welch et al [Welch et al, 2011]. 
A standard magnification of 16 is used and the variable aperture is focused on the pterygium 
from the limbus to the apex. Reading the size on the slit lamp scale, measurements are taken 
from the limbus to the apex of the lesion on the cornea and recorded to the nearest tenth of a 
millimeter. 
c. 
T2 (intermediate) or T3 (fleshy) grade in study eye at the screening (day -60 to day -7) and 
baseline (day 1) visits, using the Pterygium Morphology Grading Scale. Pterygium Morphology 
Grading Scale is classified as T1 = atrophic, T2 = intermediate, T3 = fleshy based upon the 
pterygium morphology photographic-based clinical grading system created by Tan and 
colleagues [Tan et al, 1997]. 
i. T1 (Atrophic): Pterygium in which episcleral vessels underlying the body of the 
pterygium are unobscured and clearly distinguished. 
ii. T2 (Intermediate): Pterygium in which episcleral vessel details are indistinctly seen or 
partially obscured. 
iii. T3 (Fleshy): Thick pterygium in which episcleral vessels underlying the body of the 
pterygium are totally obscured. Pterygium vessels are distinguished from episcleral 
vessels by the straightened radial orientation of the pterygium vessels. 
• 
Pterygium recurrence, defined as the presence of corneal vessels with concomitant conjunctival 
vascularity of ≥ Grade 3 after excision surgery of primary pterygium. 
• 
All patients of both genders 18 years of age or older 
Able to provide written informed consent and comply with study assessments for the full duration of the study. 
Major Exclusion Criteria 
• 
Uncontrolled systemic disease 
• 
Active ocular disease, corneal abnormalities other than pterygium, active ocular infection, or any ocular 
pathology unrelated to pterygium in either eye that could affect the assessment of the pterygium 
• 
History of ocular herpes disease in either eye 
• 
Any retina disease that could affect visual acuity (e.g., age-related macular degeneration) 
• 
Any ocular surgical procedure within the last 3 months 
• 
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 Day 1 visit. Patients wearing rigid gas 
permeable or hard contact lenses should discontinue wearing them at least 3 weeks prior to Day 1 visit 
• 
Female patients who are pregnant, nursing, or planning a pregnancy during the study 
• 
Current enrollment in an investigational drug or device study or participation in such a study within 
30 days prior to entry into this study 
• 
History of myocardial infarction or stroke 
• 
Any condition or situation which, in the investigator’s opinion, may put the patient at significant risk, 
may confound the study results, or may interfere significantly with the patient’s participation in the 
study 
• 
Known allergy or sensitivity to the study medication(s) or its components 


• 
Double pterygium (i.e., eye with nasal and temporal pterygia)  
• 
Pterygium that would require surgery 
• 
Pingueculae, pseudo-pterygia (e.g., chemical or thermal burn, trauma, marginal corneal disease); 
neoplasia (e.g., carcinoma in situ, squamous cell carcinoma, other neoplastic diseases)  
• 
Current or anticipated use of topical ophthalmic medications in the study eye. Patients must have 
discontinued use of ophthalmic medications in the study eye for at least 2 weeks prior to Day 1 visit. 
• 
Eye: an eye does not qualify for the study if any of these criteria are present. However, if none of these 
criteria are present in the other eye, the patient may still qualify for enrollment based on that eye 
provided the patient/eye meets all the inclusion and none of the exclusion criteria. 
Test Product, Dose and Mode of Administration, Batch Number: CBT-001 ophthalmic solution of vehicle or 
the highest tolerable dose (e.g., 0.2%), unilateral topical ocular dosing 
Duration of Treatment: 28 days of continuous unilateral ocular dosing with follow-up period of 1, 3, and 5-month 
post dose 
Study Measurements:  
Safety: 
• 
Ocular: visual acuity, intraocular pressure, biomicroscopy, ophthalmoscopy 
Systemic: vital signs, clinical laboratory (Chem-panel), hematology 
Adverse event reporting 
Efficacy:  
Primary Efficacy Endpoint: 
Comparison between drug-treated and vehicle-treated groups on changes of the severity grade of pterygium 
vascularity from baseline (Day 1) at Week 4; 
 
Secondary Efficacy Endpoints:  
Comparison between drug-treated and vehicle-treated groups on change from baseline (Day 1) at Weeks 2, 4, 8, 16 
and 24 in: 
• 
Corneal lesion length, defined from the anterior edge of the limbus onto the central cornea 
• 
Corneal lesion area; 
• 
Corneal lesion width; 
 
Comparison between drug-treated and vehicle-treated groups on changes of the severity grade of pterygium 
vascularity from baseline (Day 1) at Weeks 2, 8, 16 and 24; 
 
Changes from baseline (Day 1) at Weeks 2, 4, 8, 16, and 24 in: 
• 
Corneal lesion length 
• 
Corneal lesion area 
• 
Corneal lesion width 
 
Change in severity grade of pterygium vascularity from baseline (Day 1) at Weeks 2, 4, 8, 16, and 24 


 
Comparison between drug-treated and vehicle-treated groups on change from baseline (Day 1) at Weeks 2, 4, 8, 16 
and 24 in: 
• 
Topographic astigmatism in diopters 
 
Comparison between drug-treated and vehicle-treated groups on change from baseline (Day 1) at Weeks 2, 4, 8, 16 
and 24 in: 
Scores of Pterygium Symptom and Life Quality (PSLQ) questionnaire 
Statistical Methods: Two database locks are planned for the study, interim and final. The interim analysis will be 
performed after at least 80% of patients have completed their week 4 visit or discontinued prematurely. The final 
analysis will be performed after study completion.  
 
The O’Brien-Fleming group-sequential method will be used for a multiple-comparison adjustment of p-values for 
efficacy due to analyzing the data for both interim and final analyses. For the final analysis, a 2-sided test with p-
value ≤ 0.048 will be considered statistically significant for all between and within treatment comparisons. 
 
• 
In general, continuous data will be summarized with descriptive statistics (number of patients, 
mean, standard deviation, median, minimum and maximum) and will be analyzed using analysis 
of variance (ANOVA) techniques or 2-sample t-tests for between-group comparisons, and paired 
t-tests for within-group analyses. Categorical variables will be summarized by sample size (N), 
frequency count and percent, and analyzed using Pearson’s chi-square test or Fisher’s exact 
test. Ordinal variables will be analyzed using the Cochran-Mantel-Haenszel (CMH) or the 
Wilcoxon rank-sum test for between-treatment comparisons and the sign-rank test for within-
treatment comparisons. No imputation for missing data will be performed. 
Duration of Study Follow-Up: 1, 3, and 5 months after the completion of 28 days of continuous ocular dosing. 
 


ATTACHMENT: SCHEDULE OF EVENTS 
Study Procedures 
Screening 
Days -60 
to -7 
Day 1a 
Week 2 
(± 5 
days) 
Week 
4 
(± 5 
days) 
Week 
8 
(± 7 
days) 
Week 
16 
(± 7 
days) 
Week 
24 
(± 7 
days) 
Informed Consent/Authorization  
X 
 
 
 
 
 
 
Inclusion/Exclusion Criteria  
X 
X 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical / Ocular History 
X 
 
 
 
 
 
 
Pregnancy Test 
X 
X 
X 
 
 
 
 
Serious Medical Events (SME) 
X 
X 
 
 
 
 
 
Subject ID Assignment 
X 
 
 
 
 
 
 
Concomitant Medications/Concurrent 
Procedures 
X 
X 
X 
X 
X 
X 
X 
Pterygium Symptom and Life Quality 
(PSLQ) questionnaire 
X 
X 
X 
X 
X 
X 
X 
Vital Sign measurements (blood 
pressure, heart rate, body 
temperature)  
X 
X 
X 
X 
X 
X 
X 
Hematology & Blood Chemistry 
X 
 
 
X 
 
 
X 
Pterygium Photographyb 
 
X 
X 
X 
X 
X 
X 
Pterygium Vascularity Assessment 
X 
X 
 
 
 
 
 
Pterygium Morphology Assessment 
X 
X 
 
 
 
 
 
Pterygium Size Assessment  
X 
X 
 
 
 
 
 
Biomicroscopy  
X 
X 
X 
X 
X 
X 
X 
Topographic Astigmatism 
X 
X 
X 
X 
X 
X 
X 
Best-Corrected Visual Acuity  
X 
X 
X 
X 
X 
X 
X 
Intraocular Pressure  
X 
X 
X 
X 
X 
X 
X 
Ophthalmoscopy (dilated) 
X 
X 
 
X 
 
 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
Randomization  
 
X 
 
 
 
 
 
Study Medication  
 
Dispense 
Collect  Collect Collect 
 
 
Exit  
 
 
 
 
 
 
X 
a 
All measurements at baseline Day 1 are prior to the instillation of first dose 
b 
Efficacy endpoints will be assessed using pterygium photography at an independent image reading center