Molokini: Exploratory Study of KPI-121 Effect on Intra- or Subretinal Fluid Due to Retinal Vein Occlusion/Diabetic Macular Edema

• Sponsor: Kala Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02245516
• Collaborator: (none)
• Enrollment: 16
• Locations: 2
• Arms: 2
• Duration (Months): 5
• Patients Per Site: 8
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The primary objectives of the study are to evaluate the safety and effect of KPI-121 0.25% ophthalmic suspension and KPI-121 1.0% ophthalmic suspension on intraretinal or subretinal fluid secondary to Retinal Vein Occlusion or Diabetic Macular Edema.

Condition or Disease	Intervention/Treatment	Phase
Retinal Vein Occlusion; Diabetic Macular Edema	Drug: KPI-121 0.25% Ophthalmic Suspension; Drug: KPI-121 1.0% Ophthalmic Suspension	N/A

Detailed Description

This is a multicenter, randomized, single-masked study evaluating the safety and effect of topical ocular administration of either KPI-121 0.25% ophthalmic suspension or KPI-121 1.0% ophthalmic suspension in subjects with intraretinal or subretinal fluid secondary to Retinal Vein Occlusion or Diabetic Macular Edema.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: An Exploratory, Multi-Center, Randomized, Single-Masked Study Evaluating the Effect of KPI-121 on Intraretinal or Subretinal Fluid Secondary to Retinal Vein Occlusion or Diabetic Macular Edema
• Study Start Date: Jul 1, 2014
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: KPI-121 0.25% Ophthalmic Suspension KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema	Drug: KPI-121 0.25% Ophthalmic Suspension; KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.; Other Names: Loteprednol etabonate 0.25%
Active Comparator: KPI-121 1.0% Ophthalmic Suspension KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema	Drug: KPI-121 1.0% Ophthalmic Suspension; KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.; Other Names: Loteprednol etabonate 1.0%

Outcome Measures

Primary Outcome Measures

1. Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) [Day 1 to Day 57]

   Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.

2. Macular Volume by SD-OCT [Day 1 to Day 57]

   Change in measurement (in microns) in macular volume as measured by Spectral Domain Optical Coherence Tomography (OCT)

3. Center Subfield Retinal Thickness by SD-OCT [Day 1 to Day 57]

   Change in measurement (in microns) in the central subfield retinal thickness as measured by Spectral Domain Optical Coherence Tomography (OCT)

4. Investigator's Assessment of Leakage on the Fluorescein Angiogram [Day 1 to Day 57]

   Change in leakage by investigator's assessment of the fluorescein angiogram

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have documented presence of intraretinal or subretinal fluid secondary to Retinal Vein Occlusion or Diabetic Macular Edema at Screening

Exclusion Criteria:

• Treatment with topical, intravitreal injection, posterior sub-Tenon's, or periocular corticosteroids within 120 days prior to Visit 1 and for the duration of the study

• History of uncontrolled glaucoma, IOP over 21 mmHg at Visit 1, or are being treated for glaucoma in the study eye

• Any significant ocular disease that could compromise vision in the study eye (including ongoing ocular infection, wet age-related macular degeneration, myopic degeneration with active subfoveal choroidal neovascularization)

• Known hypersensitivity or contraindication to the investigational product(s) or their components

• Diagnosis of severe/serious ocular condition that in the judgment of the Investigator could confound study assessments or limit compliance; or severe/serious systemic disease or uncontrolled medical condition that in the judgment of the Investigator could confound study assessments or limit compliance

• Exposed to an investigational drug within 30 days prior to Visit 1 and for the duration of the study

• In the opinion of the Investigator or study coordinator, an unwillingness or inability to comply with the study protocol or inability to successfully instill eye drops

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
2	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Kala Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kala Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02245516
• Other Study ID Numbers: KPI-121-C-004
• First Posted: Sep 19, 2014
• Last Update Posted: Dec 10, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by Kala Pharmaceuticals, Inc.: Intraretinal Fluid; Subretinal Fluid; Retinal Vein Occlusion; Diabetic Macular Edema
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Loteprednol Etabonate

Study Results

Participant Flow

Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension	KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Period Title: Overall Study
STARTED	9	7
COMPLETED	9	4
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension	KPI-121 0.25% Ophthalmic Suspension	Total
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	Total of all reporting groups
Overall Participants	9	7	16
Age, Customized (years) [Mean (Standard Deviation) ]
Age (years)	63.2 (12.93)	65.4 (10.34)	64.2 (11.54)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	2 28.6%	4 25%
Male	7 77.8%	5 71.4%	12 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 33.3%	1 14.3%	4 25%
White	6 66.7%	6 85.7%	12 75%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	9 100%	7 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Best Corrected Visual Acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS)
Description	Best Corrected Visual Acuity (BCVA) was measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score starting at 4 meters. More letters read correctly results in a higher letter score, which represents better visual acuity.
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Intent to treat- all subjects randomized

Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension	KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Measure Participants	9	7
Mean (Standard Deviation) [ETDRS letters]	-0.9 (7.83)	-2.0 (2.00)

2. Primary Outcome

Title	Macular Volume by SD-OCT
Description	Change in measurement (in microns) in macular volume as measured by Spectral Domain Optical Coherence Tomography (OCT)
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Intent to Treat (all randomized subjects) minus subjects in each treatment group that discontinued the study prior to this time point or otherwise did not have this assessment completed

Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension	KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Measure Participants	9	4
Mean (Standard Deviation) [mm^3]	-0.237 (1.1607)	-0.377 (0.8190)

3. Primary Outcome

Title	Center Subfield Retinal Thickness by SD-OCT
Description	Change in measurement (in microns) in the central subfield retinal thickness as measured by Spectral Domain Optical Coherence Tomography (OCT)
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Intent to Treat (all randomized subjects) minus subjects in each treatment group that discontinued the study prior to this time point or otherwise did not have this assessment completed

Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension	KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Measure Participants	9	4
Mean (Standard Deviation) [micrometers (μm)]	-8.2 (52.37)	4.8 (13.99)

4. Primary Outcome

Title	Investigator's Assessment of Leakage on the Fluorescein Angiogram
Description	Change in leakage by investigator's assessment of the fluorescein angiogram
Time Frame	Day 1 to Day 57

Outcome Measure Data

Analysis Population Description

Unable to analyze the FA data for efficacy. The efficacy variable defined in the protocol was the mean change from baseline in total area of fluorescein leakage and unfortunately the total area was not collected during the study.

Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension	KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.	KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were collected from the time a subjects signed the informed consent until they exited the study at the end of Visit 5 (up to 57 days).
Arm/Group Title	KPI-121 1.0% Ophthalmic Suspension		KPI-121 0.25% Ophthalmic Suspension
Arm/Group Description	KPI-121 1.0% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 1.0% Ophthalmic Suspension: KPI-121 drug product will be supplied a 1.0% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.		KPI-121 0.25% Ophthalmic Suspension dosed QID for 4 weeks in subjects with Retinal Vein Occlusion or Diabetic Macular Edema KPI-121 0.25% Ophthalmic Suspension: KPI-121 drug product will be supplied a 0.25% loteprednol etabonate as a suspension packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.
All Cause Mortality
	KPI-121 1.0% Ophthalmic Suspension		KPI-121 0.25% Ophthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	KPI-121 1.0% Ophthalmic Suspension		KPI-121 0.25% Ophthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		1/7 (14.3%)
General disorders
generalized weakness	0/9 (0%)		1/7 (14.3%)
Other (Not Including Serious) Adverse Events
	KPI-121 1.0% Ophthalmic Suspension		KPI-121 0.25% Ophthalmic Suspension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/9 (33.3%)		2/7 (28.6%)
Eye disorders
Increase in floaters	1/9 (11.1%)	1	0/7 (0%)	0
Pain	1/9 (11.1%)	1	0/7 (0%)	0
Punctate Epithelial Erosions	1/9 (11.1%)	1	0/7 (0%)	0
Soreness	0/9 (0%)	0	1/7 (14.3%)	1
General disorders
generalized weakness	0/9 (0%)	0	1/7 (14.3%)	1
Worsening of Hypercholesterolemia	0/9 (0%)	0	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

No submission for publication or public disclosure will be made by the PI until after the publication of the results of the multi-center clinical trial by the Sponsor. Thereafter, PI shall provide KALA with an advance copy of any proposed publication or public disclosure at least sixty (60) days prior to the planned date of submission or disclosure and KALA shall have forty-five (45) days from the date of its receipt to recommend changes.