Evaluation of the Efficacy and Safety of Aceclidine/Brimonidine (LNZ101) and Aceclidine (LNZ100) in the Treatment of Presbyopia

• Status: Recruiting
• Trial end date: 2022-07-01
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate the safety and efficacy of Aceclidine/Brimonidine (LNZ101) compared with Aceclidine (LNZ100) and vehicle in the treatment of Presbyopia.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: LENZ Therapeutics, Inc
• Collaborator: ORA, Inc.
• Treatments: Aceclidine; Brimonidine Tartrate; Ophthalmic Solutions; Pharmaceutical Solutions

Criteria

Inclusion Criteria:

Subjects MUST:

1. Be able and willing to provide written informed consent and sign Health Information Portability and Accountability Act (HIPAA) form prior to any study procedure being performed;

2. Be able and willing to follow all instructions and attend study visits;

3. Be 45-75 years of age of either sex and any race or ethnicity at Visit 1;

4. Have +1.00 to -4.00 diopter (D) of sphere (so that SE results in myopia no more severe than -4.00 SE. See Inclusion 5 below) in both eyes determined by manifest refraction documented at Visit 1;

5. Have up to 2.00 D of cylinder (minus cylinder) in both eyes determined by manifest refraction documented at Visit 1;

6. Be presbyopic as determined at Visit 1 with monocular and binocular BCDVA at 40 cm as follows:

1. Cohort 1 (Approximately 20% of population, or 12 subjects): Have baseline monocular (in at least one eye) and binocular BCDVA at 40 cm greater than or equal to 0.42 and less than 0.50 logMAR (approximately between 20/50-2 and 20/63 Snellen) at Visit 1 baseline assessed prior to placebo run-in.

2. Cohort 2 (80% of population, or 48 subjects): Have baseline monocular (in at least one eye) and binocular BCDVA at 40 cm greater than or equal to 0.50 logMAR (approximately 20/63 Snellen) at Visit 1 baseline assessed prior to placebo run-in.

7. Binocular BCDVA at 40 cm must be better than, or no more than 0.1 logMAR worse than, the monocular BCDVA at 40cm for the best eye;

8. For pseudophakic subjects, intraocular lens (IOL) must be confirmed monofocal and with no significant posterior capsular opacification (PCO);

9. Have a negative urine pregnancy test at Visit 1, if female of childbearing potential (those who have experienced menarche and who are not surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral oophorectomy] or post-menopausal [12 months after last menses]) and must use adequate birth control throughout the study period. Adequate birth control is defined as hormonal - oral, implantable, injectable, or transdermal contraceptives; mechanical - spermicide in conjunction with a barrier such as condom or diaphragm; intrauterine device (IUD); or surgical sterilization of partner. For non-sexually active females, abstinence may be regarded as an adequate method of birth control;

10. Be able and willing to avoid all disallowed medications for the appropriate washout period and during the study without significant risk to the subject.

Exclusion Criteria:

Subjects must NOT:

1. Be a female of childbearing potential who is currently pregnant, nursing or planning a pregnancy;

2. Have known contraindications or sensitivity to the use of any of the study medications(s) or their components;

3. Have an active ocular infection at Visit 1 (bacterial, viral or fungal), positive history of an ocular herpetic infection, preauricular lymphadenopathy, or ongoing, active ocular inflammation (e.g., moderate to severe blepharitis, allergic conjunctivitis, peripheral ulcerative keratitis, scleritis, uveitis) in either eye;

4. Have moderate or severe dry eye defined as total corneal fluorescein staining > 2 (Ora CalibraTM Scale) in either eye at Visit 1;

5. Have clinically significant abnormal lens findings (e.g., cataract) including early lens changes and/or any evidence of a media opacity in either eye during dilated slit-lamp biomicroscopy and fundus exam documented within 3 months of Visit 1;

6. Have greater than +0.75 D hyperopic shift in sphere from manifest refraction compared to cycloplegic refraction in either eye documented within 3 months of Visit 1 or at Visit 1;

7. Have greater than 0.2 logMAR (i.e., 10 letters) difference between eyes as determined by screening monocular BCDVA at 40 cm at Visit 1;

8. Have less than 0.3 logMAR (i.e., 15-letters) improvement in monocular BCDVA at 40 cm with +1.50 D Sphere Add compared to baseline monocular BCDVA at 40 cm in the eye or eyes with monocular BCDVA at 40 cm between 0.42 and 0.70 logMAR (approximately between 20/50-1 and 20/100 Snellen) documented within 3 months of Visit 1;

9. Have greater than 0.14 logMAR (i.e., 7 letters) improvement in (placebo) post-treatment monocular BCDVA at 40 cm compared to screening monocular BCDVA in either eye at 40 cm' at Visit 1;

10. Have dark-adapted pupillometry measurements of < 4.0 mm in either eye;

11. Have intraocular pressure (IOP) that is less than 5 millimeters of mercury (mmHg) or greater than 22 mmHg in either eye documented at Visit 1, or have a prior diagnosis of ocular hypertension or glaucoma or currently being treated with any type of topical IOP lowering (glaucoma) medication at Visit 1;

12. Have abnormal findings on dilated fundus exam in either eye documented within 3 months of Visit 1 or a known history of retinal detachment or clinically significant retinal disease in either eye;

13. Have a known history or diagnosis in the past of: iritis, scleritis or uveitis, whether active or inactive;

14. Have had surgical intervention (ocular or systemic) within 6 months prior to Visit 1, or planned surgical intervention within 30 days after Visit 4;

15. Have undergone small incision lenticule extraction (SMILE), corneal inlay procedures, or multifocal intraocular lens placement;

16. Have undergone prior LASIK or PRK surgery within 12 months of Baseline Visit

a. Patients who have undergone LASIK or PRK more than 12 months prior to Baseline Visit must qualify based on all other IE criteria.

17. Use artificial tears or lubricant eye ointment on a daily basis;

18. Planned use artificial tears on the day of or during Visit 1, Visit 2, Visit 3 and Visit 4;

19. Have an inability or refuse to discontinue soft contact lens wear 7 days prior to study Visit 1 and rigid gas permeable (RGP) contact lens wear 14 days prior to Visit 1 and during the study;

20. Use any of the following disallowed medications during the 2 weeks (14 days) prior to Visit 1 and during the study:

1. narcotic (opiate class) pain medication (eg, codeine, OxyContin®, Vicodin®, Tramadol®)

2. bladder medication (eg Urecholine®, bethanechol)

3. antipsychotics

4. antidepressants

5. attention -deficit/hyperactivity disorder (ADHD) medications

6. alpha-blockers (e.g., tamsulosin, Flomax®, Jayln®, Uroxatral®, Rapaflo®)

7. anticholinergics (e.g., atropine, belladonna, benztropine, dicyclomine, donepezil, hyoscyamine, propantheline, scopolamine, trihexphenidyl)

8. muscarinic receptor agonists or cholinergic agonists (e.g., Salagen®, Evoxac®)

9. over-the-counter (OTC) or prescription antihistamines or decongestants

10. any prescribed topical ophthalmic medications

11. recreational drug use (e.g., marijuana, methadone, heroin, cocaine);

21. Have a diagnosis of diabetes mellitus or a history of elevated blood sugar;

22. Have undergone any prior corneal surgery that is not described and allowed in other IE criteria;

23. Have a condition or a situation, which in the Investigator's opinion, may put the subject at increased risk, confound study data, or interfere significantly with the subject's study participation, including but not limited to unstable: cardiovascular, hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, hematologic, neurologic, or psychiatric disease.