VEGA-2: Safety and Efficacy of Nyxol Eye Drops as a Single Agent and With Adjunctive Low-Dose Pilocarpine Eye Drops in Subjects With Presbyopia

Sponsor

Ocuphire Pharma, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05646719

Collaborator

(none)

320

Enrollment

Arms

12.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The objectives of this study are:

To evaluate the safety and efficacy of Nyxol alone and with adjunctive low dose pilocarpine to improve distance-corrected near visual acuity (DCNVA) in subjects with presbyopia.

Condition or Disease	Intervention/Treatment	Phase
Presbyopia	Drug: Phentolamine Opthalmic Solution 0.75% Other: Placebo Drug: Low dose pilocarpine Other: Low dose pilocarpine vehicle	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

320 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Study of the Safety and Efficacy of Nyxol (Phentolamine Ophthalmic Solution 0.75%) as a Single Agent and With Adjunctive Low-Dose Pilocarpine Hydrochloride Ophthalmic Solution 0.4% in Subjects With Presbyopia

Anticipated Study Start Date :

Dec 12, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nyxol + low dose pilocarpine	Drug: Phentolamine Opthalmic Solution 0.75% phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist Other Names: Nyxol Drug: Low dose pilocarpine Pilocarpine hydrochloride ophthalmic solution 0.4% Other Names: Pilocarpine LDP
Experimental: Nyxol + low dose pilocarpine vehicle	Drug: Phentolamine Opthalmic Solution 0.75% phentolamine ophthalmic solution 0.75% (Nyxol), a non-selective alpha-1 and alpha-2 adrenergic antagonist Other Names: Nyxol Other: Low dose pilocarpine vehicle Vehicle for low dose pilocarpine
Experimental: Placebo + low dose pilocarpine	Other: Placebo Vehicle for Phentolamine Ophthalmic Solution Other Names: Phentolamine Ophthalmic Solution Vehicle Drug: Low dose pilocarpine Pilocarpine hydrochloride ophthalmic solution 0.4% Other Names: Pilocarpine LDP
Placebo Comparator: Placebo + low dose pilocarpine vehicle	Other: Placebo Vehicle for Phentolamine Ophthalmic Solution Other Names: Phentolamine Ophthalmic Solution Vehicle Other: Low dose pilocarpine vehicle Vehicle for low dose pilocarpine

Outcome Measures

Primary Outcome Measures

Percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA in Nyxol-treated subjects [Visit 2 at 12 hours post-Nxyol/placebo]
The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA from Baseline in Nyxol-treated subjects at 12 hours post-Nyxol/placebo at Visit 2

Secondary Outcome Measures

Percent of subjects with ≥ 15 letters improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA in LDP+Nyxol-treated subjects [Visit 5 at 0.5 hours post-LDP/vehicle]
The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA at 0.5 hours post-LDP/vehicle at Visit 5
Percent of subjects with ≥ 15 letters improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA in Nyxol-treated subjects [Visit 2 at 0.5, 1, 3, 5 and 8 hours post-Nyxol/placebo]
The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA from Baseline in Nyxol-treated subjects at 0.5, 1, 3, 5 and 8 hours post-Nyxol/placebo at Visit 2
Percent of subjects with ≥ 15 letters improvement in photopic binocular DCNVA and with < 5 letters of loss in in photopic binocular BCDVA in LDP+Nyxol-treated subjects [Visit 5 at 1, 3, 5 and 8 hours post-LDP/vehicle]
The percent of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA and with < 5 letters of loss in photopic binocular BCDVA at 1, 3, 5 and 8 hours post-LDP/vehicle in LDP+Nyxol-treated subjects at Visit 5
Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular distance-corrected intermediate visual acuity (DCIVA) from Baseline in Nyxol-treated subjects [Visit 2 at 0.5, 1, 3, 5, 8 and 12 hours post-Nyxol/placebo]
Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular DCIVA from Baseline in Nyxol-treated subjects at 0.5, 1, 3, 5, 8 and 12 hours post-Nyxol/placebo at Visit 2
Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular DCIVA from Baseline in LDP+Nyxol-treated subjects [Visit 5 at 0.5, 1, 3, 5 and 8 hours post-LDP/vehicle]
Percentage of subjects with ≥ 5, ≥ 10, and ≥ 15 letters of improvement in photopic binocular DCIVA from Baseline in LDP+Nyxol-treated subjects at 0.5, 1, 3, 5 and 8 hours post-LDP/vehicle on Visit 5

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males or females ≥ 40 and ≤ 64 years of age.
BCDVA of 0.1 LogMAR (20/25 Snellen equivalent) or better in each eye in photopic conditions.
DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse but not > 0.7 LogMAR (20/100 Snellen equivalent) in photopic conditions in each eye and binocularly.
For subjects who depend on reading glasses or bifocals, binocular best-corrected near VA is 0.1 LogMAR (20/25 Snellen equivalent) or better.
Photopic PD of ≥ 3 mm in either eye.

Exclusion Criteria:

Ophthalmic (in either eye):

Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind within 7 days of Screening until study completion, with the exception of lid scrubs with OTC products and artificial tears as specified in Exclusion # 2 below.
Use of any OTC artificial tears (preserved or unpreserved) during Visit days or 15 min before or after instillation of study medication.
Current use of any topical ophthalmic therapy for dry eye.
Tear break-up time of < 5 seconds or corneal fluorescein staining Grade ≥ 2 in the inferior zone or Grade ≥ 1 in the central zone using the National Eye Institute scale..
Clinically significant ocular disease that might interfere with the study as deemed by the Investigator.
Recent or current evidence of ocular infection or inflammation in either eye.
Any history of herpes simplex or herpes zoster keratitis.
Known allergy, hypersensitivity, or contraindication to any component of the phentolamine, pilocarpine, or vehicle formulations.
Prior participation in a study involving the use of Nyxol for the treatment of presbyopia.
History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal.
Ocular trauma within 6 months prior to Screening.
Ocular surgery or any ocular laser treatment within 6 months prior to Screening.
Subjects with surgical monovision, multifocal or extended depth of focus intraocular lenses (IOLs) are excluded.
History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris.
Contact lens wear on the day of any study visit and contact lenses must be removed for home dosing and for at least 10 minutes following dosing.

Systemic:

Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists .
Known hypersensitivity or contraindication to any systemic cholinergic parasympathomimetic agent.
Clinically significant systemic disease that might interfere with the study as deemed by the judgment of the Investigator.
Initiation of treatment with, or any changes to, the current dosage, drug, or regimen of any systemic adrenergic or cholinergic drugs within 7 days prior to Screening or during the study.
Participation in any investigational study within 30 days prior to Screening.
Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control.
Resting HR outside the range of 50 to 110 beats per min.
Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg.