Clinical Trial of a Hydrophilic EMV Toric Lens RAO210T in the Correction of Aphakia and Corneal Astigmatism

This study is a prospective, multicenter, randomized, active controlled, masked (assessor and subject) pivotal investigation for unilateral implantation of low cylinder (1.50 D) toric IOL. It compares the Rayner RAO210T toric IOL to the Rayner RAO600C aspheric monofocal IOL. Subjects who sign the ICF are considered enrolled in the study. After signing the ICF, subjects will be screened for eligibility. Inclusion and Exclusion Criteria must be applied prior to subject randomization. Subjects who meet all protocol-specified eligibility criteria will be assigned to the randomized controlled study arms if the study eye's estimated IOL cylinder power using Barrett Toric Calculator is 1.50 D. Randomized subjects receive either the Rayner RAO210T Toric IOL (1.50 D low cylinder) or the Rayner RAO600C aspheric monofocal IOL in the study eye.

Up to 295 adult subjects will be enrolled (consented) assuming a 15% screen failure rate, then up to 250 subjects will be randomized, of which approximately 125 subjects will be randomized to receive low cylinder (1.50 D) RayOne EMV Toric (Model RAO210T) in one eye and approximately 125 subjects randomized to receive the RAO600C aspheric monofocal IOL in one eye, to complete 120-180 days follow-up for at least 100 subjects in each group.

All subjects who meet inclusion criteria will be assigned to the randomized controlled study arms to receive either the RAO210T toric IOL (1.50 D low cylinder) or the RAO600C aspheric monofocal IOL in the study eye according to a 1:1 ratio. Randomization will be stratified by site.

Up to 11 U.S. sites will be encouraged to enroll a minimum of 20 subjects. No site will enroll more than 25% of the subjects enrolled in the study.

If a subject has significant cataract in both eyes, it is recommended that cataract surgery is performed in one eye before the subject is enrolled in the study. Once a subject has been enrolled, it is recommended that the fellow eye does not undergo cataract surgery (except for a YAG capsulotomy) throughout the duration of the study. At screening, if both eyes qualify for the study, the eye to undergo cataract surgery and IOL implantation is the eye with worse pre-operative BCDVA. If pre-operative BCDVA is the same for each eye, the right eye will be the study eye.

Subjects will complete 6 study visits in approximately 9 months. Subject participation is calculated as the difference between the time of the pre-operative visit to completion of Visit 4 (120 to 180 days post-operative).

Standard clinical trial methods will be used to minimize bias, such as the use of site personnel performing manifest refraction and visual acuity assessments masked to subject treatment assignment, masking of subjects in the randomized controlled investigation evaluating low cylinder power, standardized test procedures, common Investigator training and common inclusion and exclusion criteria.

In order to minimize bias, measures will be taken to mask the site personnel performing post-operative manifest refraction and visual acuity assessments, as to the subject's treatment assignment until after the final database lock. Every attempt should be made to have the same masked site personnel perform the same masked post-operative assessments for an individual subject throughout the subject's study participation.

Subjects will be masked to their IOL assignment in the randomized controlled investigation evaluating low cylinder power. All material which may indicate the subjects' assignment, e.g., packaging, documents, etc., will be removed from any areas where subjects and/or masked site personnel may see them. Unmasked personnel will further be instructed to scrupulously avoid conversation and communication with masked personnel, subjects and all other persons regarding subjects' assignments, outcomes, clinical courses, and all other information potentially relevant to the study and its conduct.

Study Groups:

• Toric (test) group - all subjects randomized to be implanted with the low cylinder (1.50 D) RayOne EMV Toric IOL (Model RAO210T)
• Monofocal (control) group - all subjects randomized to be implanted with the RAO600C Monofocal IOL

Sample Size Determination:

Subjects will be enrolled with the goal of completing a total of 200 subjects through Visit 4 within the randomized groups, of whom 100 were implanted with the low cylinder RayOne EMV Toric IOL (Model RAO210T) and 100 were implanted with the RAO600C monofocal IOL.

Effectiveness For effectiveness, 100 subjects (eyes) randomized to the Toric (test) group (lowest cylinder power +1.50D) and 100 subjects (eyes) randomized to the Monofocal (control) group completing Visit 4 yields over 98% statistical power to reject H0e in favor of H1e and conclude the Toric IOL has statistically significantly lower mean residual manifest cylinder at Visit 4 compared to the Monofocal IOL, using a one-sided t-test with an alpha level of 0.025 and assuming a true mean difference of 0.4 D and a standard deviation of 0.7 D in both groups.

Safety For safety, ISO 11979-7 and ANSI Z80.30 specifies that a minimum of 100 subjects should complete a clinical evaluation of an IOL, where a parent IOL has been approved, to obtain appropriate specificity around adverse event and visual acuity rates.

Handling of Missing Data:

Missing data will be imputed for selected endpoints using the methods specified under the analysis descriptions for the endpoints. Where possible, multiple imputation will be used. Except where mentioned in Section 7, missing data will not be imputed.

Multiplicity Considerations:

The overall type I error rate for the toric effectiveness analyses will be controlled at 0.05. The study will be considered successful if all of the primary effectiveness and safety endpoints are met. Thus, no adjustments for multiplicity are necessary.

All primary effectiveness and primary safety endpoints as described below are required to achieve successful outcomes in order to demonstrate study success.