A Clinical Investigation of the ClarVista HARMONI™ Modular Intraocular Lens Implant Following Cataract Surgery

Study Overview
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Brief Summary
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The main objectives of this feasibility study were: To demonstrate the feasibility of HARMONI Modular Intraocular Lens (HMIOL) implantation and assembly in subjects undergoing cataract surgery (All HMIOL Cohort), and To demonstrate the feasibility of the HMIOL optic component exchange procedure (performed 3 months following primary cataract extraction) (Cohort 2).

Detailed Description
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Eligible subjects with bilateral cataracts underwent cataract extraction and IOL implantation using phacoemulsification. The study eye was implanted with the investigational device (All HMIOL Cohort). The fellow eye was treated with a commercially available intraocular lens (IOL) per standard of care procedure. At the scheduled Month 3 post-operative visit, subjects who did not opt to pursue an optic exchange procedure in the study eye were enrolled into subgroup Cohort 1 and followed for an additional 6 months. The total duration of participation for Cohort 1 was up to 15 months, which included a Day -90 to Day -1 preoperative period and a 12 month post-operative follow-up period. At the scheduled Month 3 post-operative visit, subjects who elected to pursue an optic exchange procedure in the study eye were enrolled into subgroup Cohort 2 and followed for an additional 12 months. The total duration of participation for Cohort 2 was up to 18 months, which included a Day -90 to Day -1 preoperative period, an optic exchange at Month 3 postoperative, and a 12 month post-exchange follow-up period. Alcon Research, LLC, acquired ClarVista Medical in 2017. This study was designed and conducted by ClarVista Medical, Inc., to evaluate the safety and effectiveness of the HMIOL. The study results were collected, analyzed, and provided by ClarVista Medical, Inc. to Alcon Research, LLC.

Official Title
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A Prospective, Multi-Center, Feasibility Trial of the ClarVista HARMONI™ Modular Intraocular Lens System for the Treatment of Aphakia Following Cataract Surgery

Conditions
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Cataract

Intervention / Treatment
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* Device: Harmoni Modular Intraocular Lens
* Device: Commercially Available Intraocular Lens
* Procedure: Optic exchange


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to understand and provide informed consent Must be willing and able to return for scheduled treatment and follow-up examinations for up to 15 month study duration Planned bilateral removal of visually significant bilateral cataracts Best-corrected distance visual acuity (BCDVA) projected to be better than 20/32 after IOL implantation in both eyes Preoperative bilateral BCDVA of 20/40 or worse Both eyes must have corneal astigmatism ≤ 1.50 diopter (D) Women must be post-menopausal ≥1 year or surgically sterilized, or a pregnancy screen must be performed prior to the study and a reliable form of contraception, approved by the investigator, must be maintained during the study Dilated pupil size equal to or greater than 6 millimeters (mm) in primary study eye Other protocol-specified inclusion criteria may apply. Exclusion Criteria: Participation in any other drug or device clinical trial within 30 days prior to enrolling in this study and/or during study participation History of any intraocular or corneal surgery in either eye (including refractive) History of any clinically significant retinal pathology or ocular diagnosis in either eye History of any ocular conditions which could affect the stability of the IOL Uncontrolled glaucoma in either eye Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All HMIOL Cohort<br>HMIOL implantation with or without optic exchange | Device: Harmoni Modular Intraocular Lens<br>* Two-component system consisting of a base and a separate optic that allows for an intraoperative exchange of the optic only without direct manipulation of the capsular bag<br>* Other names: HMIOL;|
| Experimental: Cohort 1<br>HMIOL implantation with no optic exchange | Device: Harmoni Modular Intraocular Lens<br>* Two-component system consisting of a base and a separate optic that allows for an intraoperative exchange of the optic only without direct manipulation of the capsular bag<br>* Other names: HMIOL;|
| Experimental: Cohort 2<br>HMIOL implantation with optic exchange | Device: Harmoni Modular Intraocular Lens<br>* Two-component system consisting of a base and a separate optic that allows for an intraoperative exchange of the optic only without direct manipulation of the capsular bag<br>* Other names: HMIOL;Procedure: Optic exchange<br>* Removal of one optic and replacement with another for the purpose of improving refractive outcomes<br>|
| Other: Fellow Eye<br>IOL implantation per standard of care | Device: Commercially Available Intraocular Lens<br>* IOL per investigator's standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - All HMIOL Cohort | Visual acuity (VA) was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS)-Fast method under well-lit conditions at a distance of 4 meters (m) with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative | 
| Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Cohort 1 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative | 
| Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Cohort 2 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Month 1 postoperative and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned | Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange | 
| Percentage of Eyes With Postoperative BCDVA 20/40 Snellen or Better by Study Visit - Fellow Eye | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative, Month 12 postoperative | 
| Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - All HMIOL Cohort | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. The manifest refraction spherical equivalent (MRSE) was calculated as follows: sphere + 1/2 cylinder, and measured in diopters (D). This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Week 1 postoperative, Month 1 postoperative, Month 3 postoperative | 
| Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Cohort 1 | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. The manifest refraction spherical equivalent (MRSE) was calculated as follows: sphere + 1/2 cylinder, and measured in diopters (D). This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative | 
| Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Cohort 2 | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. The manifest refraction spherical equivalent (MRSE) was calculated as follows: sphere + 1/2 cylinder, and measured in diopters (D). An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange | 
| Percentage of Eyes With Postoperative Manifest Refraction Spherical Equivalent (MRSE) Within Target by Study Visit - Fellow Eye | A manifest refraction (manual vision test) was conducted using letter charts and a phoropter. The manifest refraction spherical equivalent (MRSE) was calculated as follows: sphere + 1/2 cylinder, and measured in diopters (D). This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned. | Month 1 postoperative, Month 3 postoperative, Month 12 postoperative | 
| Mean BCDVA (Letters Read) by Study Visit - All HMIOL Cohort | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Day -90 to Day -1 preoperative, Month 1 postoperative, Month 3 postoperative | 
| Mean BCDVA (Letters Read) by Study Visit - Cohort 1 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative | 
| Mean BCDVA (Letters Read) by Study Visit - Cohort 2 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was recorded in letters read correctly. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Month 1 postoperative and Month 3 postoperative visits were pre-optic exchange.This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange | 
| Mean BCDVA (Letters Read) by Study Visit - Fellow Eye | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with the correction obtained from manifest refraction testing. BCDVA was rrecorded in letters read correctly. This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned. | Day -90 to -1 preoperative, Month 1 postoperative, Month 3 postoperative, Month 12 postoperative | 
| Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - All HMIOL Cohort | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative | 
| Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Cohort 1 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative | 
| Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Cohort 2 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye. No formal statistical hypothesis testing was planned. | Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Day 1 post-optic exchange, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exch | 
| Mean Uncorrected Distance Visual Acuity (UCDVA) (Letters Read) by Study Visit - Fellow Eye | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in letters read correctly. This analysis was prespecified for the fellow eye. No formal statistical hypothesis testing was planned. | Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, Month 3 postoperative, Month 6 postoperative, Month 12 postoperative | 
| Percentage of Eyes With UCDVA by Category (Snellen) for Each Post-optic Exchange Study Visit - Cohort 2 | VA was assessed using the ETDRS-Fast method under well-lit conditions at a distance of 4 m with an optical infinity adjustment of +0.25 diopter (D). UCDVA was recorded in Snellen, with 20/20 considered to be 'normal' vision. A visual acuity of 20/40 means the participant is able to read a certain size letter 20 feet away that a person with 'normal' vision would be able to read from 40 feet away. An optic exchange occurred at the Month 3 visit, after which subjects were followed for an additional 12 months. Day 1 postoperative, Week 1 postoperative, Month 1 postoperative, and Month 3 postoperative visits were pre-optic exchange. This analysis was prespecified for the study eye, Cohort 2 only. No formal statistical hypothesis testing was planned. | Day 1 post-optic exchange, Week 1 post-optic exchange, Month 1 post-optic exchange, Month 3 post-optic exchange, Month 6 post-optic exchange, Month 12 post-optic exchange | 
| Mesopic Best Corrected Distance Visual Acuity (mBCDVA) (With and Without Glare) (Letters Read) at Study Visit - All HMIOL Cohort | VA was assessed using the ETDRS-Fast method under mesopic (dimly lit) conditions at a distance of 4 m with the correction obtained from manifest refraction testing. Testing was performed with and without glare. Chart luminance was set to 3 cd/m2. mBCDVA was recorded in letters read correctly. This analysis was prespecified for the study eye, All HMIOL Cohort only. No formal statistical hypothesis testing was planned. | Month 3 postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cataract, IOL, Modular IOL, IOL exchange