Clinical Investigation of the Clareon® Intraocular Lens (IOL)

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03170154
• Collaborator: (none)
• Enrollment: 376
• Locations: 16
• Arm: 1
• Actual Duration (Months): 18.7
• Patients Per Site: 23.5
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The objective of this study is to compare visual acuity and adverse event outcomes from the Clareon intraocular lens (IOL) to historical safety and performance endpoint (SPE) rates.

Condition or Disease	Intervention/Treatment	Phase
Cataract	Device: Clareon aspheric hydrophobic acrylic monofocal IOL	N/A

Detailed Description

Upon meeting eligibility criteria, subjects were implanted unilaterally (in one eye) with a Clareon IOL. Subjects attended 7 study visits over a period of approximately 13 months, including 1 preoperative screening visit (Visit 0), 1 operative visit (Visit 00), and 5 postoperative visits (Visits 1-5). Visit day calculations for Visits 1-5 were based off of the day of surgery (Visit 00). Primary endpoint data was collected at the final visit (Month 12). Some sites/subjects participated in a Rotational Stability sub-study. For the non-study eye, the investigator followed standard of care regarding the follow-up, surgery, and intraocular lens choice (as applicable). The non-study eye (fellow eye) was not implanted with the Clareon IOL.

Study Design

• Study Type: Interventional
• Actual Enrollment: 376 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Investigation of the Clareon® IOL
• Actual Study Start Date: Jul 25, 2017
• Actual Primary Completion Date: Feb 15, 2019
• Actual Study Completion Date: Feb 15, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Clareon IOL Clareon aspheric hydrophobic acrylic monofocal IOL implanted in one eye during routine small incision cataract surgery	Device: Clareon aspheric hydrophobic acrylic monofocal IOL; Ultraviolet-absorbing and blue light-filtering IOL composed of high refractive-index foldable and flexible acrylic material. IOLs are implantable medical devices intended for long term use over the lifetime of the cataract subject.

Outcome Measures

Primary Outcome Measures

1. Percentage of All-implanted Subjects Achieving Monocular Best Corrected Distance Visual Acuity (BCDVA) of 0.3 logMAR or Better at Month 12 Postoperative [Month 12 (postoperative)]

   Visual acuity (VA) of the study eye was assessed with best refractive correction in place under photopic (well-lit) conditions at a distance of 4 meters using Early Treatment Diabetic Retinopathy Study (ETDRS) letter charts. As pre-specified in the protocol, the percentage of subjects with monocular BCDVA of 0.3 logMAR or better at Month 12 was compared to the historical safety and performance endpoint (SPE) rate reported in EN ISO 11979-7:2014. A higher percentage indicates good visual acuity outcomes with most subjects achieving 0.3 logMAR or better.

2. Percentage of Best-case Subjects Achieving Monocular BCDVA of 0.3 logMAR or Better at Month 12 Postoperative [Month 12 (postoperative)]

   Visual acuity (VA) of the study eye was assessed with best refractive correction in place under photopic conditions at a distance of 4 meters using an Early Treatment Diabetic Retinopathy Study (ETDRS) letter charts. As pre-specified in the protocol, the percentage of subjects with monocular BCDVA of 0.3 logMAR or better at Month 12 was compared to the historical safety and performance endpoint (SPE) rate reported in EN ISO 11979-7:2014. A higher percentage indicates good visual acuity outcomes with most subjects achieving 0.3 logMAR or better.

3. Percentage of Subjects With Adverse Events (Ocular and Nonocular, Serious and Nonserious), Including Secondary Surgical Interventions (SSIs) - Study Eye [Day 0 (operative), up to Month 12 (postoperative)]

   Adverse events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. No hypothesis testing was pre-specified in the protocol.

Secondary Outcome Measures

1. Mean Absolute IOL Rotation [Day 0 (operative), Month 6 (postoperative)]

   IOL rotation was defined as the difference between axis of IOL orientation on the day of surgery and Month 6. IOL rotation and measured with slit-lamp photography. No hypothesis testing was pre-specified in the protocol. A lower number indicates minimal IOL rotation at 6 months.

2. Mean Absolute IOL Misplacement [Day 0 (operative)]

   IOL misplacement was defined as the difference between intended axis of placement and actual axis of IOL orientation on day of surgery. IOL misplacement was measured using slit lamp photography. No hypothesis testing was pre-specified in the protocol. A lower number indicates minimal IOL misplacement.

3. Mean Absolute IOL Misalignment [Day 0 (operative), Month 6 (postoperative)]

   IOL misalignment was defined as the summation of IOL misplacement and IOL rotation at Month 6. No hypothesis testing was pre-specified in the protocol. A lower number indicates minimal IOL misalignment at 6 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Planned routine cataract surgery in at least one eye;

• Calculated lens power within the available range;

• Willing and able to sign an informed consent statement;

• Clear intraocular media other than cataract.

Key Exclusion Criteria:

• Any disease or pathology, other than cataract, that is expected to reduce the potential postoperative best corrected distance visual acuity (BCDVA) to a level worse than 0.30 logMAR;

• Previous corneal surgery;

• Rubella or traumatic cataract;

• Ocular trauma, previous refractive surgery;

• Current or recent use of certain medications as specified in the protocol;

• Any other ocular or systemic condition that, in the opinion of the Investigator, should exclude the subject from the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alcon Investigative Site	Fresno	California	United States	93720
2	Alcon Investigative Site	Sacramento	California	United States	95815
3	Alcon Investigative Site	San Leandro	California	United States	94578
4	Alcon Investigative Site	Deerfield Beach	Florida	United States	33064
5	Alcon Investigative Site	Orland Park	Illinois	United States	60467
6	Alcon Investigative Site	Bloomfield Hills	Michigan	United States	48302
7	Alcon Investigative Site	Kansas City	Missouri	United States	64154
8	Alcon Investigative Site	New York	New York	United States	10013
9	Alcon Investigative Site	Poughkeepsie	New York	United States	12603
10	Alcon Investigative Site	Elizabeth City	North Carolina	United States	27909
11	Alcon Investigative Site	Southern Pines	North Carolina	United States	28387
12	Alcon Investigative Site	Florence	South Carolina	United States	29501
13	Alcon Investigative Site	Ladson	South Carolina	United States	29456
14	Alcon Investigative Site	Austin	Texas	United States	78731
15	Alcon Investigative Site	Nacogdoches	Texas	United States	75965
16	Alcon Investigative Site	Appleton	Wisconsin	United States	54914

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Sr. Clinical Trial Lead, CDMA Surgical, Alcon Research, LLC

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 1, 2018
• Study Protocol - Feb 19, 2018

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT03170154
• Other Study ID Numbers: ILJ466-C001
• First Posted: May 30, 2017
• Last Update Posted: Aug 3, 2020
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Cataract

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at 16 investigative sites located in the United States.
Pre-assignment Detail	Of the 376 enrolled, 26 subjects did exit the study as screen failures. This reporting group (350) includes all subjects with attempted implantation with the IOL (successful or aborted after contact with the eye).

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Period Title: Overall Study
STARTED	350
Rotational Stability Sub-study	141
COMPLETED	342
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Overall Participants	350
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.7 (6.44)
Sex: Female, Male (Count of Participants)
Female	213 60.9%
Male	137 39.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 3.1%
Not Hispanic or Latino	336 96%
Unknown or Not Reported	3 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	29 8.3%
Native Hawaiian or Other Pacific Islander	1 0.3%
Black or African American	36 10.3%
White	273 78%
More than one race	0 0%
Unknown or Not Reported	11 3.1%
Region of Enrollment (participants) [Number]
United States	350 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of All-implanted Subjects Achieving Monocular Best Corrected Distance Visual Acuity (BCDVA) of 0.3 logMAR or Better at Month 12 Postoperative
Description	Visual acuity (VA) of the study eye was assessed with best refractive correction in place under photopic (well-lit) conditions at a distance of 4 meters using Early Treatment Diabetic Retinopathy Study (ETDRS) letter charts. As pre-specified in the protocol, the percentage of subjects with monocular BCDVA of 0.3 logMAR or better at Month 12 was compared to the historical safety and performance endpoint (SPE) rate reported in EN ISO 11979-7:2014. A higher percentage indicates good visual acuity outcomes with most subjects achieving 0.3 logMAR or better.
Time Frame	Month 12 (postoperative)

Outcome Measure Data

Analysis Population Description

All-Implanted Subjects (AAS): All subjects/eyes with successful IOL implantation and data at visit

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Measure Participants	342
Measure eyes	342
Number (95% Confidence Interval) [percentage of subjects]	99.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clareon IOL
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	1-sided 95% Upper CL
	Estimated Value	99.99
	Confidence Interval	(1-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Historical comparison to EN ISO 11979-7:2014: SPE rate of at least 92.5 for the AAS at 12 months.

2. Primary Outcome

Title	Percentage of Best-case Subjects Achieving Monocular BCDVA of 0.3 logMAR or Better at Month 12 Postoperative
Description	Visual acuity (VA) of the study eye was assessed with best refractive correction in place under photopic conditions at a distance of 4 meters using an Early Treatment Diabetic Retinopathy Study (ETDRS) letter charts. As pre-specified in the protocol, the percentage of subjects with monocular BCDVA of 0.3 logMAR or better at Month 12 was compared to the historical safety and performance endpoint (SPE) rate reported in EN ISO 11979-7:2014. A higher percentage indicates good visual acuity outcomes with most subjects achieving 0.3 logMAR or better.
Time Frame	Month 12 (postoperative)

Outcome Measure Data

Analysis Population Description

Best-Case Analysis Set (BAS): All subjects/eyes successfully implanted with the IOL that had at least 1 postoperative visit, no preoperative ocular pathology, no macular degeneration at any time, and no previous surgery for the correction of refractive errors, with data at visit.

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Measure Participants	326
Measure eyes	326
Number (95% Confidence Interval) [percentage of subjects]	99.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clareon IOL
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	1-sided 95% Upper CL
	Estimated Value	99.98
	Confidence Interval	(1-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Historical comparison to EN ISO 11979-7:2014: SPE rate of at least 96.7 for the BAS at 12 months.

3. Primary Outcome

Title	Percentage of Subjects With Adverse Events (Ocular and Nonocular, Serious and Nonserious), Including Secondary Surgical Interventions (SSIs) - Study Eye
Description	Adverse events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. No hypothesis testing was pre-specified in the protocol.
Time Frame	Day 0 (operative), up to Month 12 (postoperative)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set (SAS): All subjects/study eyes with attempted implantation with the test article (successful or aborted after contact with the eye)

Arm/Group Title	Pre-treatment	Clareon IOL - Ocular	Systemic
Arm/Group Description	Events reported in this group occurred prior to attempted implantation with the test article and may include ocular events in the study eye, as well as overall systemic events.	Events reported in this group occurred after attempted implantation with the test article and include ocular events in the study eye.	Events reported in this group occurred after attempted implantation with the test article.
Measure Participants	350	350	350
Serious Adverse Events	0	2.3	4.0
Non-Serious Adverse Events	1.4	27.1	15.1

4. Secondary Outcome

Title	Mean Absolute IOL Rotation
Description	IOL rotation was defined as the difference between axis of IOL orientation on the day of surgery and Month 6. IOL rotation and measured with slit-lamp photography. No hypothesis testing was pre-specified in the protocol. A lower number indicates minimal IOL rotation at 6 months.
Time Frame	Day 0 (operative), Month 6 (postoperative)

Outcome Measure Data

Analysis Population Description

Rotation Analysis Set (RAS): All subjects/eyes with successful IOL implantation from the rotational subset of 6 clinical sites, with rotation data available at operative visit and Month 6 visit.

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Measure Participants	124
Measure eyes	124
Mean (Standard Deviation) [degrees]	2.2696 (3.87231)

5. Secondary Outcome

Title	Mean Absolute IOL Misplacement
Description	IOL misplacement was defined as the difference between intended axis of placement and actual axis of IOL orientation on day of surgery. IOL misplacement was measured using slit lamp photography. No hypothesis testing was pre-specified in the protocol. A lower number indicates minimal IOL misplacement.
Time Frame	Day 0 (operative)

Outcome Measure Data

Analysis Population Description

RAS: All subjects/eyes with successful IOL implantation from the rotational subset of 6 clinical sites, with rotation data available at operative visit.

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Measure Participants	131
Measure eyes	131
Mean (Standard Deviation) [degrees]	5.1163 (4.90305)

6. Secondary Outcome

Title	Mean Absolute IOL Misalignment
Description	IOL misalignment was defined as the summation of IOL misplacement and IOL rotation at Month 6. No hypothesis testing was pre-specified in the protocol. A lower number indicates minimal IOL misalignment at 6 months.
Time Frame	Day 0 (operative), Month 6 (postoperative)

Outcome Measure Data

Analysis Population Description

RAS, with rotation data available at operative visit and Month 6 visit

Arm/Group Title	Clareon IOL
Arm/Group Description	Clareon aspheric hydrophobic acrylic monofocal intraocular lens (IOL) implanted in one eye during routine small incision cataract surgery
Measure Participants	124
Measure eyes	124
Mean (Standard Deviation) [degrees]	5.6762 (6.42510)

Adverse Events

Time Frame	Adverse events were collected pre-treatment (Day -30 to 0) up to Month 12 post-treatment/study exit. Adverse events (AEs) were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator.
Adverse Event Reporting Description	This analysis population includes all subjects/eyes with attempted implantation with the test article (successful or aborted after contact with the eye). "At Risk" population of pre-treatment and systemic AEs is reported in units of subjects; ocular AE population is reported in units of eyes. For the non-study eye (fellow eye), the investigator followed standard of care regarding the follow-up, surgery, and IOL choice (as applicable). The non-study eye was not implanted with Clareon IOL.
Arm/Group Title	Pre-treatment		Clareon IOL - Ocular (Study Eye)		Systemic and Ocular Non-Study (Non-Clareon) Eye
Arm/Group Description	Events reported in this group occurred prior to attempted implantation with the test article and may include ocular events in the study eye and non-study eye (fellow eye), as well as overall systemic events. The non-study eye was not implanted with Clareon IOL.		Events reported in this group occurred after attempted implantation with the test article and include ocular events in the study eye.		Events reported in this group occurred after attempted implantation with the test article and may include ocular events in the non-study eye (fellow eye), as well as overall systemic events. The non-study eye was not implanted with Clareon IOL.
All Cause Mortality
	Pre-treatment		Clareon IOL - Ocular (Study Eye)		Systemic and Ocular Non-Study (Non-Clareon) Eye
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/350 (0%)		0/350 (0%)		2/350 (0.6%)
Serious Adverse Events
	Pre-treatment		Clareon IOL - Ocular (Study Eye)		Systemic and Ocular Non-Study (Non-Clareon) Eye
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/350 (0%)		8/350 (2.3%)		18/350 (5.1%)
Blood and lymphatic system disorders
Lymphadenopathy	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Cardiac disorders
Acute myocardial infarction	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Atrial fibrillation	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Myocardial infarction	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Eye disorders
Cystoid macular oedema	0/350 (0%)	0	3/350 (0.9%)	3	1/350 (0.3%)	1
Macular fibrosis	0/350 (0%)	0	1/350 (0.3%)	1	0/350 (0%)	0
Macular hole	0/350 (0%)	0	1/350 (0.3%)	1	0/350 (0%)	0
Punctate keratitis	0/350 (0%)	0	1/350 (0.3%)	1	2/350 (0.6%)	2
Retinal tear	0/350 (0%)	0	2/350 (0.6%)	2	1/350 (0.3%)	1
Gastrointestinal disorders
Dysphagia	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
General disorders
Death	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Hepatobiliary disorders
Cholelithiasis	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Infections and infestations
Herpes virus infection	0/350 (0%)	0	1/350 (0.3%)	1	0/350 (0%)	0
Pneumonia	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Septic shock	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Injury, poisoning and procedural complications
Subdural haematoma	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Traumatic intracranial haemorrhage	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Breast cancer	0/350 (0%)	0	0/350 (0%)	0	2/350 (0.6%)	2
Nervous system disorders
Cerebral artery embolism	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Cerebral haematoma	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Hemiplegia	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Surgical and medical procedures
Corneal operation	0/350 (0%)	0	1/350 (0.3%)	2	2/350 (0.6%)	2
Hip arthroplasty	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Ophthalmologic treatment	0/350 (0%)	0	1/350 (0.3%)	1	0/350 (0%)	0
Radical hysterectomy	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Retinal laser coagulation	0/350 (0%)	0	2/350 (0.6%)	2	0/350 (0%)	0
Retinopexy	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Urostomy	0/350 (0%)	0	0/350 (0%)	0	1/350 (0.3%)	1
Vitrectomy	0/350 (0%)	0	2/350 (0.6%)	2	0/350 (0%)	0
Other (Not Including Serious) Adverse Events
	Pre-treatment		Clareon IOL - Ocular (Study Eye)		Systemic and Ocular Non-Study (Non-Clareon) Eye
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/350 (1.7%)		19/350 (5.4%)		127/350 (36.3%)
Eye disorders
Posterior capsule opacification	0/350 (0%)	0	19/350 (5.4%)	19	18/350 (5.1%)	18
Surgical and medical procedures
Cataract operation	6/350 (1.7%)	6	0/350 (0%)	0	117/350 (33.4%)	117

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.