Safety and Efficacy of KPI-121 in Subjects With Postsurgical Inflammation (Hawaii-1)

A Phase III, Double-Masked, Randomized, Controlled Trial of KPI-121 in Postsurgical Inflammation

The primary purpose of this study is to determine the efficacy and safety of KPI-121 ophthalmic suspension compared to placebo in subjects who have undergone cataract surgery. The efficacy and safety of two different concentrations and two different dosing regimens of KPI-121 are also being assessed.

Study Overview

• Status: Completed
• Conditions: Ocular Infections, Irritations and Inflammations
• Intervention / Treatment: Drug: KPI-121 0.25%; Drug: KPI-121 1.0%; Drug: Vehicle of KPI-121 0.25%; Drug: Vehicle of KPI-121 1.0%

Detailed Description

This is a Phase III, multicenter, double-masked, randomized, placebo-controlled, parallel-group study designed to evaluate the efficacy and safety of two doses and two dosing regimens of KPI-121 ophthalmic suspension versus placebo in subjects who require treatment of postoperative anterior ocular inflammation.

Approximately 500 subjects will be screened and up to 402 subjects with one study eye each will be randomized in this study at approximately 25 centers located in the United States. Subjects who experience postoperative inflammation on the first day following routine, uncomplicated, cataract surgery and who meet all other eligibility criteria will be randomized to one of four study groups (0.25% four times daily or 1.0% two times daily) or Placebo A four times daily or Placebo B two times daily. Drug product or placebo will be initiated on the day following surgery and instilled as one to two drops in the study eye according to the assigned dosing regimen for 14 days.

This study will include up to 7 clinic visits (including the surgery day) over 18 to 33 days total study duration. Visit 1 (Screening) will occur between 14 to 1 day(s) prior to surgery, and subjects who meet preoperative screening inclusion/exclusion criteria will be entered into the study. At Visit 2 (Surgery/Day 0) subjects will undergo routine cataract surgery according to the Investigator's normal procedures. Visit 3 (Randomization/Day 1) will occur on the day following surgery.

Following randomization, subjects will be instructed to return to the clinic to be evaluated at Visit 4 (Day 3 +2 day), Visit 5 (Day 8 ±1 day), and Visit 6 (Day 15 ±1 day). The last dose of study product will be administered upon completion of 14 days of evaluation. Following the End of Study Product Use Visit (Visit 6; Day 15 ±1 day), subjects will be asked to return to the clinic on Day 17-19 for Visit 7 (Follow-Up) and will be released from the study.

• Study Type: Interventional
• Enrollment (Actual): 380
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
    • Mission Hills, California, United States, 91345
      • North Valley Eye Medical Group
    • Rancho Cordova, California, United States, 95670
      • Martel Eye Medical Group
    • Torrance, California, United States, 90505
      • Wolstan & Goldberg Eye Associates
  • Georgia
    • Morrow, Georgia, United States, 30260
      • Clayton Eye Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group
    • New Albany, Indiana, United States, 47150
      • John-Kenyon American Eye Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Taustine Eye Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
    • Saint Louis, Missouri, United States, 63131
      • Ophthalmology Associates
    • Saint Louis, Missouri, United States, 63128
      • Tekwani Vision Center
    • Saint Louis, Missouri, United States, 63131
      • Ophthalmology Consultants
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Las Vegas Physicians Research Group
  • New York
    • New York, New York, United States, 10013
      • Raymond Fong, MDPC
    • Rochester, New York, United States, 14618
      • Rochester Ophthalmological Group, PC
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Cornerstone Eye Care
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Cincinnati Eye Institute
    • Columbus, Ohio, United States, 43215
      • The Eye Center of Columbus
  • South Carolina
    • Spartanburg, South Carolina, United States, 29306
      • Westside Research, LLC
  • Texas
    • League City, Texas, United States, 77573
      • The Eye Clinic of Texas, Affiliate of Houston Eye Associates
    • San Antonio, Texas, United States, 78229
      • R&R Eye Research, LLC
    • San Antonio, Texas, United States, 78230
      • Kozlovsky Delay & Winter Eye Consultants, LLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Eye Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

FURTHER STUDY DETAILS PROVIDED BY KALA PHARMACEUTICALS, INC.

Inclusion Criteria:

• Candidates for routine, uncomplicated cataract surgery
• In Investigator's opinion, potential postoperative Snellen Distance VA by pinhole method of at least 20/200 in study eye.

Exclusion Criteria:

• Known hypersensitivity/contraindication to study product(s) or components.
• History of glaucoma, IOP >21 mmHg at the screening or randomization visits, or being treated for glaucoma in either eye.
• Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; severe/serious systemic disease or uncontrolled medical condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within the 30 days prior to screening or 19 days following surgery.
• In the opinion of Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: KPI-121 0.25% QID; KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.	Drug: KPI-121 0.25%; KPI-121 drug product will be supplied as 0.25% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.; Other Names: Loteprednol etabonate 0.25%; KPI-121 0.25% Ophthalmic Suspension
Active Comparator: KPI-121 1.0% BID; KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.	Drug: KPI-121 1.0%; KPI-121 drug product will be supplied as 1.0% as a suspension in identically packaged opaque dropper bottles. KPI-121 drug product is a sterile, aqueous, submicron suspension of loteprednol etabonate.; Other Names: Loteprednol etabonate 1.0%; KPI-121 1.0% Ophthalmic Suspension
Placebo Comparator: Vehicle of KPI-121 0.25%; Vehicle of KPI-121 0.25% Ophthalmic Suspension dosed 4 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.	Drug: Vehicle of KPI-121 0.25%; Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.; Other Names: Vehicle of KPI-121 0.25% Ophthalmic Suspension
Placebo Comparator: Vehicle of KPI-121 1.0%; Vehicle of KPI-121 1.0% Ophthalmic Suspension dosed 2 times daily for 14 days after routine, uncomplicated surgery for cataract removal and intraocular lens implant.	Drug: Vehicle of KPI-121 1.0%; Placebo control arms will receive the same bottles containing vehicle of KPI-121 including all components at the concentrations used in the KPI-121 drug product with the exception of the active component, loteprednol etabonate.; Other Names: Vehicle of KPI-121 1.0% Ophthalmic Suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Resolution of Anterior Chamber Cells	Subjects with complete resolution of anterior chamber cells (cell score = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6. 0= No cells seen; 1 to 5 cells; 6 to 15 cells; 16 to 30 cells; greater than 30 cells	Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15)
Resolution of Ocular Pain	Subjects with complete resolution of pain (grade = 0) without rescue medication at Day 8/Visit 5 and Day 15/Visit 6.	Visit 5 (postoperative day 8) and Visit 6 (postoperative day 15)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anterior Chamber Cell Grade at Visit 5.	Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 5/Day 8. The difference in mean grade of AC cell count grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen; 1 - 5 cells; 6 - 15 cells; 16 - 30 cells 4 = greater than 30 cells	Visit 5 (postoperative day 8)
Anterior Chamber Cell Grade at Visit 6.	Mean Grade of Anterior Chamber Cells (Scale 0-4) at Visit 6/Day 15. The difference in mean grade of AC cell count grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Investigators were asked to grade AC cell based on the following scale wherein higher scores indicate a higher degree of cells present and a decrease across time indicates the condition is getting better. Anterior Chamber Cells 0 = No cells seen; 1 - 5 cells; 6 - 15 cells; 16 - 30 cells 4 = greater than 30 cells	Visit 6 (postoperative day 15)
Ocular Pain Grades at Day 8.	Mean Grade of Ocular Pain (Scale 0-5) at Visit 5/Day 8. The difference in mean grade of ocular pain grade at Day 8 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None; Minimal; Mild; Moderate; Moderately Severe; Severe	Visit 5 (postoperative day 8)
Ocular Pain Grades at Day 15.	Mean Grade of Ocular Pain (Scale 0-5) at Visit 6/Day 15. The difference in mean grade of ocular pain grade at Day 15 for KPI-121 1% dosed twice daily (BID) or 0.25% dosed four times daily (QID) compared with vehicle (either dosed BID or QID). Subjects were given the Subject-Rated Ocular Pain Assessment to subjectively rate their pain. Higher scores were worse outcomes. The following scoring scale was used for ocular pain: 0 = None; Minimal; Mild; Moderate; Moderately Severe; Severe	Visit 6 (postoperative day 15)

Collaborators and Investigators

• Sponsor: Kala Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 12, 2014
• First Submitted That Met QC Criteria: June 12, 2014
• First Posted (Estimate): June 16, 2014

Study Record Updates

• Last Update Posted (Actual): January 29, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: pain; inflammation; cataract; corticosteroid; postoperative; ocular; postsurgical
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Eye Diseases; Inflammation; Eye Infections; Anti-Allergic Agents; Loteprednol Etabonate
• Other Study ID Numbers: KPI-121-C-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO