Safety and Efficacy of CBT-001 Ophthalmic Solution in Patients With Pterygium

• Sponsor: Cloudbreak Therapeutics, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03049852
• Collaborator: (none)
• Enrollment: 75
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.5
• Patients Per Site Per Month: 6

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Pterygium	Drug: CBT-001 single dose; Drug: Vehicle; Drug: CBT-001 Multi-dose	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Apr 15, 2017
• Actual Primary Completion Date: Apr 30, 2018
• Actual Study Completion Date: Apr 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CBT-001 Ophthalmic Solution Single dose One drop in the study administered one time only for one day	Drug: CBT-001 single dose; One drop in the study administered one time
Placebo Comparator: Vehicle One drop in the study administered three times daily (TID) for 4 weeks	Drug: Vehicle; One drop in the study administered three times daily (TID) for 4 weeks
Experimental: CBT-001 Ophthalmic Solution Multidose One drop in the study administered three times daily (TID) for 4 weeks	Drug: CBT-001 Multi-dose; One drop in the study administered three times daily (TID) for 4 weeks

Outcome Measures

Primary Outcome Measures

1. Pterygium Vascularity Change Assessed Using the Pterygium Hyperemia Grading Scale [Change from baseline at 4 weeks]

   The primary efficacy variable is the change from baseline (Day 1) in severity grade of pterygium vascularity at Week 4. Pterygium vascularity intensity is based on color coordinates as measured by digital image analysis of pterygium photographs. The quantitative analysis of photographs using a 5-point Pterygium Hyperemia Grading Scale (0 = absent, 1 = trace, 2 = mild, 3 = moderate, 4 = severe) will be conducted at an independent image reading center.

2. Ocular and General Safety and Tolerability [One day]

   The ocular safety and tolerability are measured 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

Secondary Outcome Measures

1. Corneal Pterygium Lesion Length Change From Baseline [4 weeks]

   The Corneal Pterygium Lesion Length is measured from digital images of the eye by an independent image reading center.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary pterygium with moderate vascularity (Pterygium Hyperemia Grading Scale ≥ 3)

Exclusion Criteria:

• 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 ocular surgical procedure within the last 3 months

• Female patients who are pregnant, nursing, or planning a pregnancy during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Harvard Eye Associates	Laguna Beach	California	United States	92651

Sponsors and Collaborators

• Cloudbreak Therapeutics, LLC

Investigators

• Principal Investigator: John Hovanesian, M.D., Harvard Eye Associates

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 12, 2017

More Information

Publications

None provided.

• Responsible Party: Cloudbreak Therapeutics, LLC
• ClinicalTrials.gov Identifier: NCT03049852
• Other Study ID Numbers: CBT-CS101
• First Posted: Feb 10, 2017
• Last Update Posted: Feb 24, 2020
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Pterygium

Study Results

Participant Flow

Arm/Group Title	CBT-001 Ophthalmic Solution Single Dose	Vehicle Multi-dose	CBT-001 Ophthalmic Solution Multi-dose
Arm/Group Description	CBT-001 Ophthalmic Solution Single dose in one day	One drop in the study administered three times daily (TID) for 4 weeks	One drop in the study administered three times daily (TID) for 4 weeks
Period Title: Overall Study
STARTED	24	25	26
COMPLETED	24	24	26
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	CBT-001 Ophthalmic Solution Single Dose	Vehicle Multi-dose	CBT-001 Ophthalmic Solution Multi-dose	Total
Arm/Group Description	One drop in the study administered one time CBT-001: One drop in the study administered one time	One drop in the study administered three times daily (TID) for 4 weeks Vehicle: One drop in the study administered three times daily (TID) for 4 weeks	One drop in the study administered three times daily (TID) for 4 weeks CBT-001: One drop in the study administered three times daily (TID) for 4 weeks	Total of all reporting groups
Overall Participants	24	25	26	75
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.8 (11.6)	49.4 (10.7)	52.0 (12.1)	50.7 (11.4)
Sex: Female, Male (Count of Participants)
Female	13 54.2%	11 44%	14 53.8%	38 50.7%
Male	11 45.8%	14 56%	12 46.2%	37 49.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	1 3.8%	1 1.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	24 100%	21 84%	24 92.3%	69 92%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	4 16%	1 3.8%	5 6.7%
Region of Enrollment (participants) [Number]
United States	24 100%	25 100%	26 100%	75 100%

Outcome Measures

1. Primary Outcome

Title	Pterygium Vascularity Change Assessed Using the Pterygium Hyperemia Grading Scale
Description	The primary efficacy variable is the change from baseline (Day 1) in severity grade of pterygium vascularity at Week 4. Pterygium vascularity intensity is based on color coordinates as measured by digital image analysis of pterygium photographs. The quantitative analysis of photographs using a 5-point Pterygium Hyperemia Grading Scale (0 = absent, 1 = trace, 2 = mild, 3 = moderate, 4 = severe) will be conducted at an independent image reading center.
Time Frame	Change from baseline at 4 weeks

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	Vehicle Multi-dose	CBT-001 Ophthalmic Solution Multi-dose
Arm/Group Description	One drop in the study administered three times daily (TID) Vehicle: One drop in the study administered three times daily (TID) for 4 weeks	One drop in the study administered three times daily (TID) CBT-001: One drop in the study administered three times daily (TID) for 4 weeks
Measure Participants	23	25
Mean (Standard Deviation) [grade]	0 (0.5)	-0.8 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vehicle Multi-dose, CBT-001 Ophthalmic Solution Multi-dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Primary Outcome

Title	Ocular and General Safety and Tolerability
Description	The ocular safety and tolerability are measured 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
Time Frame	One day

Outcome Measure Data

Analysis Population Description

mITT

Arm/Group Title	CBT-001 Ophthalmic Solution Single Dose
Arm/Group Description	One drop in the study administered one time One drop in the study administered one time in one day
Measure Participants	24
Mild eye irritation	3 12.5%
Mild foreign body sensation	1 4.2%

3. Secondary Outcome

Title	Corneal Pterygium Lesion Length Change From Baseline
Description	The Corneal Pterygium Lesion Length is measured from digital images of the eye by an independent image reading center.
Time Frame	4 weeks

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population

Arm/Group Title	CBT-001 Ophthalmic Solution	Vehicle
Arm/Group Description	One drop in the study administered three times daily (TID) CBT-001: One drop in the study administered three times daily (TID)	One drop in the study administered three times daily (TID) Vehicle: One drop in the study administered three times daily (TID)
Measure Participants	25	23
Mean (Standard Deviation) [mm]	-0.11 (0.3)	0.16 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vehicle Multi-dose, CBT-001 Ophthalmic Solution Multi-dose
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	CBT-001 Ophthalmic Solution Single Dose		Vehicle Multi-dose		CBT-001 Ophthalmic Solution Multi-dose
Arm/Group Description	One drop in the study administered one time One drop in the study administered one time in one day		One drop in the study administered three times daily (TID) Vehicle: One drop in the study administered three times daily (TID) for 4 weeks		One drop in the study administered three times daily (TID) CBT-001: One drop in the study administered three times daily (TID) for 4 weeks
All Cause Mortality
	CBT-001 Ophthalmic Solution Single Dose		Vehicle Multi-dose		CBT-001 Ophthalmic Solution Multi-dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/25 (0%)		0/26 (0%)
Serious Adverse Events
	CBT-001 Ophthalmic Solution Single Dose		Vehicle Multi-dose		CBT-001 Ophthalmic Solution Multi-dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		1/25 (4%)		0/26 (0%)
Blood and lymphatic system disorders
Transient ischaemic attack	/24 (NaN)		1/25 (4%)	1	0/26 (0%)	0
Other (Not Including Serious) Adverse Events
	CBT-001 Ophthalmic Solution Single Dose		Vehicle Multi-dose		CBT-001 Ophthalmic Solution Multi-dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/24 (16.7%)		2/25 (8%)		20/26 (76.9%)
Eye disorders
Conjunctival Discoloration	0/24 (0%)	0	0/25 (0%)	0	14/26 (53.8%)	0
Foreign Body Sensation in Eyes	1/24 (4.2%)	1	0/25 (0%)	1	2/26 (7.7%)	1
Lacrimation Increased	0/24 (0%)	0	0/25 (0%)	0	2/26 (7.7%)	0
Eye irritation	3/24 (12.5%)	3	0/25 (0%)	0	0/26 (0%)	0
General disorders
Dysgeusia	0/24 (0%)	0	0/25 (0%)	0	2/26 (7.7%)	0
Infections and infestations
Influenza A infection	0/24 (0%)	0	2/25 (8%)	0	0/26 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.