A Single-Center, Double-Masked Evaluation of the Efficacy and Safety of PRX-100 in the Treatment of Early to Moderate Presbyopia

• Sponsor: LENZ Therapeutics, Inc (Other)
• Overall Status: Completed
• CT.gov ID: NCT03201562
• Collaborator: (none)
• Enrollment: 58
• Location: 1
• Arms: 3
• Actual Duration (Months): 12.6
• Patients Per Site Per Month: 4.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Presbyopia	Drug: Aceclidine+tropicamide combination; Drug: Aceclidine; Drug: Vehicle	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Single-Center, Double-Masked Evaluation of the Efficacy and Safety of PRX-100 in the Treatment of Early to Moderate Presbyopia
• Actual Study Start Date: Apr 30, 2017
• Actual Primary Completion Date: May 20, 2018
• Actual Study Completion Date: May 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aceclidine+tropicamide combination Aceclidine+tropicamide combination single dose (PRX-100 Ophthalmic Solution)	Drug: Aceclidine+tropicamide combination; Ophthalmic Solution; Other Names: PRX-100
Active Comparator: Aceclidine Aceclidine single dose	Drug: Aceclidine; Ophthalmic Solution
Sham Comparator: Vehicle Vehicle single dose	Drug: Vehicle; Ophthalmic Solution

Outcome Measures

Primary Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 48 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts 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:

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

16. bladder medication (eg Urecholine®, bethanechol)

17. antipsychotics

18. antidepressants

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

20. alpha-blockers (eg, tamsulosin, Flomax®, Jayln®, Uroxatral®, Rapaflo®)

21. anticholinergics (eg, atropine, belladonna, benztropine, dicyclomine, donepezil, hyoscyamine, propantheline, scopolamine, trihexphenidyl)

22. muscarinic receptor agonists or cholinergic agonists (eg, Salagen®, Evoxac®)

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

24. any prescribed topical ophthalmic medications

25. recreational drug use (eg, marijuana, methadone, heroin, cocaine);

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

27. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Andover Eye Associates	Andover	Massachusetts	United States	01810

Sponsors and Collaborators

• LENZ Therapeutics, Inc

Investigators

• Principal Investigator: Gail Torkildsen, MD, Andover Eye Associates

Study Documents (Full-Text)

• Study Protocol - Jul 3, 2018
• Statistical Analysis Plan - Jul 3, 2018

More Information

Publications

None provided.

• Responsible Party: LENZ Therapeutics, Inc
• ClinicalTrials.gov Identifier: NCT03201562
• Other Study ID Numbers: PRX100.FDAIIb
• First Posted: Jun 28, 2017
• Last Update Posted: May 14, 2021
• Last Verified: Apr 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Presbyopia; Tropicamide; Aceclidine

Study Results

Participant Flow

Arm/Group Title	Crossover Sequence 1	Crossover Sequence 2	Crossover Sequence 3
Arm/Group Description	Aceclidine+tropicamide combination Visit 1, Aceclidine Visit 2, Vehicle Visit 3	Aceclidine Visit 1, Vehicle Visit 2, Aceclidine+tropicamide combination Visit 3	Vehicle Visit 1, Aceclidine+tropicamide combination Visit 2, Aceclidine Visit 3
Period Title: Overall Study
STARTED	18	20	20
COMPLETED	18	19	16
NOT COMPLETED	0	1	4

Baseline Characteristics

Arm/Group Title	Crossover Sequence 1	Crossover Sequence 2	Crossover Sequence 3	Total
Arm/Group Description	Aceclidine+tropicamide combination Visit 1, Aceclidine Visit 2, Vehicle Visit 3	Aceclidine Visit 1, Vehicle Visit 2, Aceclidine+tropicamide combination Visit 3	Vehicle Visit 1, Aceclidine+tropicamide combination Visit 2, Aceclidine Visit 3	Total of all reporting groups
Overall Participants	18	20	20	58
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.8 (3.29)	55.7 (4.28)	56.2 (4.51)	55.6 (4.05)
Sex: Female, Male (Count of Participants)
Female	9 50%	7 35%	11 55%	27 46.6%
Male	9 50%	13 65%	9 45%	31 53.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 11.1%	0 0%	0 0%	2 3.4%
Not Hispanic or Latino	16 88.9%	20 100%	20 100%	56 96.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	2 10%	0 0%	2 3.4%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 5.6%	0 0%	0 0%	1 1.7%
White	15 83.3%	18 90%	20 100%	53 91.4%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	2 11.1%	0 0%	0 0%	2 3.4%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects With at Least a 3 Line (15 Letter) Improvement in Near Visual Acuity in the Study Eye
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Aceclidine+Tropicamide Combination	Aceclidine	Vehicle
Arm/Group Description	Aceclidine+tropicamide combination single dose	Aceclidine single dose	Vehicle single dose
Measure Participants	36	36	42
Number [percentage of participants]	47.22 262.3%	47.22 236.1%	2.38 11.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aceclidine+Tropicamide Combination, Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	Generalized Estimating Equation (GEE)
	Comments	GEE model includes 3-line improvement as response variable with sequence, period, treatment as fixed effect, subject within sequence as random effect.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	38.436
	Confidence Interval	(2-Sided) 90%; 6.262 to 235.936
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Aceclidine, Vehicle
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Generalized Estimating Equation (GEE)
	Comments	GEE model includes 3-line improvement as response variable with sequence, period, treatment as fixed effect, subject within sequence as random effect.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	36.893
	Confidence Interval	(2-Sided) 90%; 5.936 to 229.310
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Aceclidine+Tropicamide Combination, Aceclidine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9298
	Comments
	Method	Generalized Estimating Equation (GEE)
	Comments	GEE model includes 3-line improvement as response variable with sequence, period, treatment as fixed effect, subject within sequence as random effect
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.042
	Confidence Interval	(2-Sided) 90%; 0.485 to 2.239
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse Events were collected for up to 50 days.
Adverse Event Reporting Description	Safety population includes all randomized subjects who receive at least one dose of the study medication.
Arm/Group Title	Aceclidine+Tropicamide Combination		Aceclidine		Vehicle
Arm/Group Description	Aceclidine+tropicamide combination single dose		Aceclidine single dose		Vehicle single dose
All Cause Mortality
	Aceclidine+Tropicamide Combination		Aceclidine		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)		0/57 (0%)
Serious Adverse Events
	Aceclidine+Tropicamide Combination		Aceclidine		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/54 (0%)		0/54 (0%)		0/57 (0%)
Other (Not Including Serious) Adverse Events
	Aceclidine+Tropicamide Combination		Aceclidine		Vehicle
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/54 (40.7%)		22/54 (40.7%)		10/57 (17.5%)
Eye disorders
Instillation site pain (mild)	17/54 (31.5%)		16/54 (29.6%)		6/57 (10.5%)
Instillation site pain (moderate)	2/54 (3.7%)		5/54 (9.3%)		4/57 (7%)
Ocular hyperaemia	3/54 (5.6%)		0/54 (0%)		0/57 (0%)
Nervous system disorders
Headache	3/54 (5.6%)		3/54 (5.6%)		0/57 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The PI must not present the study results until the aggregate multi-site study results are published. The PI must submit to sponsor any proposed publication or presentation at least 60 days prior to the submission. Sponsor may require the delay of publication or presentation for an additional period of time not to exceed 120 days for the purposes of filing patent applications to patentable subject matter or the resolution of any inaccuracies or misleading statements.