Presbyopia
Conditions
Brief summary
To evaluate the safety and efficacy of PRX-100 compared with aceclidine alone and vehicle in the treatment of early to moderate presbyopia.
Interventions
DRUGAceclidine+tropicamide combination
Ophthalmic Solution
DRUGAceclidine
Ophthalmic Solution
DRUGVehicle
Ophthalmic Solution
Sponsors
LENZ Therapeutics, Inc
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
48 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
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 48-64 years of age of either sex and any race or ethnicity at visit 1; 4. Be an early to moderate presbyope determined by screening monocular best-corrected distance visual acuity (VA) at 45 cm 5. 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
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 (eg, moderate to severe blepharitis, allergic conjunctivitis, peripheral ulcerative keratitis, scleritis, uveitis) in either eye; 4. Have moderate or severe dry eye; 5. Have clinically significant abnormal lens findings (eg cataract) including early lens changes and/or any evidence of a media opacity in either eye; 6. Have dark-adapted pupillometry measurements of \< 4.0 mm in either eye; 7. 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; 8. 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; 9. Have a known history or diagnosis in the past of: iritis, scleritis or uveitis, whether active or inactive; 10. Have had surgical intervention (ocular or systemic) within 6 months prior to visit 1, or planned surgical intervention within 30 days after visit 4; 11. Have undergone refractive eye surgery (incisional keratotomy, photorefractive keratectomy \[PRK\], laser in situ keratomileusis \[LASIK\], laser-assisted sub-epithelial keratectomy \[LASEK\]), corneal inlay procedures, cataract extraction, or intraocular lens placement; 12. Use artificial tears or lubricant eye ointment on a daily basis; 13. 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; 14. 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 (eg, tamsulosin, Flomax®, Jayln®, Uroxatral®, Rapaflo®) 7. anticholinergics (eg, atropine, belladonna, benztropine, dicyclomine, donepezil, hyoscyamine, propantheline, scopolamine, trihexphenidyl) 8. muscarinic receptor agonists or cholinergic agonists (eg, Salagen®, Evoxac®) 9. over-the-counter (OTC) or prescription antihistamines or decongestants 10. any prescribed topical ophthalmic medications 11. recreational drug use (eg, marijuana, methadone, heroin, cocaine); 15. Have a diagnosis of diabetes mellitus or a history of elevated blood sugar; 16. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects With at Least a 3 Line (15 Letter) Improvement in Near Visual Acuity in the Study Eye | 1 hour post-treatment | Proportion of subjects with at least a 3 line (15 letter) improvement in near visual acuity in the study eye at 1 hour post-treatment in the mITT population |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Crossover Sequence 1 Aceclidine+tropicamide combination Visit 1, Aceclidine Visit 2, Vehicle Visit 3 | 18 |
| Crossover Sequence 2 Aceclidine Visit 1, Vehicle Visit 2, Aceclidine+tropicamide combination Visit 3 | 20 |
| Crossover Sequence 3 Vehicle Visit 1, Aceclidine+tropicamide combination Visit 2, Aceclidine Visit 3 | 20 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Crossover Sequence 1 | Crossover Sequence 2 | Crossover Sequence 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 3.29 | 55.7 years STANDARD_DEVIATION 4.28 | 56.2 years STANDARD_DEVIATION 4.51 | 55.6 years STANDARD_DEVIATION 4.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 20 Participants | 20 Participants | 56 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 18 Participants | 20 Participants | 53 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 11 Participants | 27 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 9 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 54 | 0 / 54 | 0 / 57 |
| other Total, other adverse events | 22 / 54 | 22 / 54 | 10 / 57 |
| serious Total, serious adverse events | 0 / 54 | 0 / 54 | 0 / 57 |
Outcome results
Primary
Proportion of Subjects With at Least a 3 Line (15 Letter) Improvement in Near Visual Acuity in the Study Eye
Proportion of subjects with at least a 3 line (15 letter) improvement in near visual acuity in the study eye at 1 hour post-treatment in the mITT population
Time frame: 1 hour post-treatment
Population: The treatment crossover design allowed for each treatment to be analyzed in all 58 subjects. The primary efficacy analysis was performed on a mITT population of subjects meeting the baseline criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aceclidine+Tropicamide Combination | Proportion of Subjects With at Least a 3 Line (15 Letter) Improvement in Near Visual Acuity in the Study Eye | 47.22 percentage of participants |
| Aceclidine | Proportion of Subjects With at Least a 3 Line (15 Letter) Improvement in Near Visual Acuity in the Study Eye | 47.22 percentage of participants |
| Vehicle | Proportion of Subjects With at Least a 3 Line (15 Letter) Improvement in Near Visual Acuity in the Study Eye | 2.38 percentage of participants |
p-value: 0.000990% CI: [6.262, 235.936]Generalized Estimating Equation (GEE)
p-value: 0.001290% CI: [5.936, 229.31]Generalized Estimating Equation (GEE)
p-value: 0.929890% CI: [0.485, 2.239]Generalized Estimating Equation (GEE)