A Study to Investigate the Effect of IOP-lowering With TO-O-1001 Eye Drops in Healthy Subjects and in Patients With Open-Angle Glaucoma or Ocular Hypertension

A 3-Part, First-in-human, Double-Blind, Randomized, and Placebo-Controlled Study Assessing the Safety, Tolerability, and Efficacy of TO-O-1001 Ophthalmic Solution in Healthy Subjects and in Patients With Open-Angle Glaucoma or Ocular Hypertension

This is a Phase I/II stage to investigate the safety, tolerability, and ocular hypotensive efficacy of TO-O-1001 in healthy volunteers and patients with Open-Angle Glaucoma or Ocular Hypertension.

The proposed trial consists of 3 study parts to be conducted at Nucleus Network Melbourne.

This study will enroll up to 34 evaluable healthy volunteers in part 1(SAD) and part 2(MD) and 16 evaluable patients with Open-Angle Glaucoma or Ocular Hypertension in part 3(MD).

Note- As of 14Mar2023, enrolment has been completed for Part 1 and Part 2 and recruitment is pending now for Part 3.

Study Overview

• Status: Active, not recruiting
• Conditions: Ocular Hypertension; Open Angle Glaucoma
• Intervention / Treatment: Drug: TO-O-1001; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network Melbourne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

For Healthy Subjects (Parts 1 & 2)

1. 18 - 59-year-old healthy male or female subjects who are non-lactating and non-pregnant.
2. BMI 18.0~32.0(kg/m2) and body weight more than 45kg.
3. Intraocular pressure between 10 - 21 mm Hg (inclusive) in each eye.
4. Best-corrected visual acuity (BCVA) in each eye of 20/40 ETRDS or better.
5. The informed consent form has been read, signed and dated by the subjects.
6. Able to communicate well with the investigator and comply with the requirements of the study.

For Patients (Part 3)

1. Must be 18 years of age or older.
2. Diagnosis of primary open angle glaucoma (POAG) or ocular hypertension (OHT).
3. Unmedicated or after washout intraocular pressure (IOP) >20 mmHg and < 30 mmHg in study eye at T0 (T0 = 08:00AM~10:00 AM) of the first qualification visit (Day 1).
4. Best-corrected visual acuity (BCVA) equivalent to 20/200 ETRDS or better.
5. The informed consent form has been read, signed and dated by the subjects.
6. Able to communicate well with the investigator and comply with the requirements of the study

Exclusion Criteria:

For Healthy Subjects (Parts 1 & 2)

1. Subjects has chronic or acute ophthalmic disease including glaucoma, macular degeneration, and clinically significant cataract (primary or secondary).
2. Subjects has previous glaucoma intraocular surgery or glaucoma laser procedures within 3 years.
3. Subjects has refractive surgery (e.g., radial keratotomy, PRK, LASIK, etc.) within 5 years.
4. Subjects has ocular trauma within the past 6 months, or ocular surgery or laser treatment within the past three months (e.g., laser treatment for glaucoma or retina).

For Patients (Part 3)

1. Closed or very narrow angles (Grade 0-1) or those the investigator judges as occludable and/or with evidence of peripheral anterior synechiae (PAS) ≥ 180 degrees by gonioscopy within 6 months prior to Screening Visit in either eye. (Patent laser iridotomy with Grade 1-2 angles is acceptable in either eye, providing the PAS criteria are still met).
2. Previous glaucoma intraocular surgery in either eye. Prior laser trabeculoplasty (ALT or SLT) in either eye is allowed if performed more than 6 months prior to Screening Visit.
3. Any non-glaucoma intraocular surgery within 3 months prior to Screening Visit in either eye.
4. Participation in a clinical study with use of any investigational drug or treatment within 28 days prior to Baseline (Day 1).
5. Clinically significant abnormalities in: laboratory tests, physical examination, vital signs and/or ECG at Screening Visit. If in the investigator's judgment a subjects with clinically significant abnormalities is appropriate for enrollment in the study, a discussion between the investigator and the Medical Monitor must occur and be documented prior to enrollment of this subjects in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (TO-O-1001); Drug: TO-O-1001 Dose level: 0.05% and 0.1% Dosage form: ophthalmic solution Route of administration: topical ocular	Drug: TO-O-1001; TO-O-1001 ophthalmic solution in two concentration (0.05% and 0.1%) ocular administration only one drop in one eye
Placebo Comparator: B (Placebo); Dosage form: ophthalmic solution Route of administration: topical ocular	Other: Placebo; The placebo is of same visual appearance and identical formulation as TO-O-1001, except the active component TO-168 ocular administration only one drop in one eye

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of TO-O-1001 though the incidence of adverse events.	Number of participants with treatment-emergent adverse events (AEs).	Up to 28 days
Evaluate the ocular hypotensive efficacy of TO-O-1001 through Goldmann Applanation Tonometry.	The primary efficacy outcome is mean IOP.	Up to 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of TO-O-1001. Blood samples obtained to evaluate the systemic exposure.	Parameter: Area Under the Curve (AUC)	Up to 8 days
Pharmacokinetics of TO-O-1001. Blood samples obtained to evaluate the systemic exposure.	Parameter: Maximum Concentration	Up to 8 days
Pharmacokinetics of TO-O-1001. Blood samples obtained to evaluate the systemic exposure.	Parameter: Maximum observed concentration (Cmax in first and last dose)	Up to 8 days
Pharmacokinetics of TO-O-1001. Blood samples obtained to evaluate the systemic exposure.	Parameter: Area under the concentration-time curve (AUC0-t and AUC0-inf in first and last dose)	Up to 8 days
Pharmacokinetics of TO-O-1001. Blood samples obtained to evaluate the systemic exposure.	Parameter: Time of observed Cmax	Up to 8 days
Pharmacokinetics of TO-O-1001. Blood samples obtained to evaluate the systemic exposure.	Parameter: Terminal elimination half-life and elimination constant in first and last dose	Up to 8 days
Best Corrected Visual Acuity (BCVA) of TO-O-1001.	Visual function of the study eye was assessed using the ETDRS protocol. A higher score represents better functioning.	Up to 28 days
Safety and tolerability of TO-O-1001 through the incidence, severity and causality of serious adverse events (SAEs).	Number of participants with treatment-emergent serious adverse events.	Up to 28 days

Collaborators and Investigators

• Sponsor: Theratocular Biotek Co.
• Collaborators: Novotech (Australia) Pty Limited
• Investigators: Principal Investigator: Sam Francis, Nucleus Network Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2022
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: June 27, 2022
• First Submitted That Met QC Criteria: July 11, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension
• Other Study ID Numbers: TO-01C101

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