A Phase 1/ Phase 2 Study of TTHX1114(NM141) (INTREPID)

A Phase 1/ Phase 2 Study Evaluating the Safety and Efficacy of the Investigational New Drug TTHX1114(NM141) on the Regeneration of Corneal Endothelial Cells in Patients With Corneal Endothelial Dystrophies Following Intracameral Delivery

Prospective, multicenter, randomized, masked, vehicle-controlled, dose-escalation study

Study Overview

• Status: Completed
• Conditions: Endothelial Dysfunction; Corneal Endothelial Dystrophy; Pseudophakic Bullous Keratopathy; Fuchs Endothelial Corneal Dystrophy
• Intervention / Treatment: Other: Vehicle (placebo); Drug: TTHX1114(NM141)

Detailed Description

This is a prospective, multi-center, randomized, masked, vehicle-controlled, dose-escalation study that will include an observational (no intervention) sub-study. Eligible subjects with moderate to severe corneal endothelial dystrophy (defined as Endothelial Cell Density < 2000 mm^2) in at least one eye will be enrolled and randomized.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Petaluma, California, United States, 94954
      • North Bay Eye Associates, Inc.
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Levenson Eye Associates, Inc
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Chicago Corneal Consultants
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
  • Nebraska
    • Omaha, Nebraska, United States, 68137
      • Vance Thompson Vision - Omaha
  • New York
    • Poughkeepsie, New York, United States, 12603
      • Alterman, Modi and Wolter
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • Vance Thompson Vision - Sioux Falls

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Fuchs Endothelial Corneal Dystrophy, pseudophakic bullous keratopathy, or endothelial dysfunction/ insufficiency due to surgical intervention diagnosed more than 6 months prior to Study Day 0
• Central endothelial cell count of < 2000 mm^2 in at least one eye as determined by the central reading facility

Key Exclusion Criteria:

• Conditions that would impair examination of the anterior chamber structure
• Documented repeated elevated intra ocular pressure (in either eye)
• Corneal transplant (in either eye)
• Posterior Polymorphous Corneal Dystrophy (PPCD)
• History of uveitis or herpetic keratitis
• Cataract surgery within the past 3 months
• Refractive surgery (in the Study Eye)
• Anterior Chamber IOL placement (in the Study Eye)
• Active extra-ocular inflammation from any non-infectious or infectious cause within the past 6 months
• Expected or planned ocular surgery within the next 3 months
• Use of cytotoxic chemotherapy within the last 1 month
• Treatment with a rho kinase inhibitor within the last 3 months
• Use of cyclosporine ophthalmic emulsion or lifitegrast ophthalmic solution in the last 30 days
• Systemic or ophthalmic corticosteroid use in the 30 days prior to Study Day 0 unless approved by the Medical Monitor
• History of significant allergy, hypersensitivity, or intolerance to any drug compound, food, or other substance
• Unwilling to use birth control

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
Placebo Comparator: Vehicle (placebo); Placebo weekly x 4	Other: Vehicle (placebo); Placebo
Experimental: Low dose; TTHX1114(NM141) low-dose weekly x 4	Drug: TTHX1114(NM141); engineered FGF-1 delivered intracamerally
Experimental: Mid-dose; TTHX1114(NM141) mid-dose weekly x 4	Drug: TTHX1114(NM141); engineered FGF-1 delivered intracamerally
Experimental: High-dose; TTHX1114(NM141) high-dose weekly x 4	Drug: TTHX1114(NM141); engineered FGF-1 delivered intracamerally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLTs/ Adverse Reactions	Suspected Adverse Reactions Reported Following Study Drug Adminsitration	Day 90

Collaborators and Investigators

• Sponsor: Trefoil Therapeutics, Inc.
• Investigators: Study Director: Thomas M Tremblay, RN BSN, Trefoil Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2020
• Primary Completion (Actual): April 23, 2021
• Study Completion (Actual): May 18, 2021

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): October 30, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Genetic Diseases, Inborn; Eye Diseases, Hereditary; Corneal Diseases; Corneal Dystrophies, Hereditary; Fuchs' Endothelial Dystrophy
• Other Study ID Numbers: TTHX-001

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No