to Evaluate the Effectiveness and Safety of the Tixel® , VS LipiFlow® in the Treatment of Meibomian Gland Dysfunction

Study Overview
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Brief Summary
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A Randomized, Masked (Evaluator), Controlled, Prospective Study Evaluating the Effectiveness and Safety of the Tixel® Medical Device, Versus LipiFlow® in the Treatment of Meibomian Gland Dysfunction

Detailed Description
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Randomized, open-label study comparing the Tixel device to LipiFlow System. Up to 110 patients (220 eyes) to be randomized in up to 5 clinical sites in the United States. Evaluators will be masked as to the randomization assignments. Both eyes will receive the same randomized assignment and both eyes of each patient will be evaluated at all time points. Data from both eyes will be using in the statistical analysis. The random-effects model adjusts the standard error (SE) and the confidence interval (CI) for within-person correlation between eyes. Protocol Rev. 7.0 update: Addition of protocol extension to the current protocol: stage 1- main protocol for all patients and stage 2- extension protocol to a sub-group of patients only in the Tixel arm for additional follow-up visit 6 months post last treatment.

Official Title
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A Randomized, Masked (Evaluator), Controlled, Prospective Study Evaluating the Effectiveness and Safety of the Tixel® Medical Device, Versus LipiFlow® in the Treatment of Meibomian Gland Dysfunction

Conditions
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Meibomian Gland Dysfunction, Dry Eye Syndromes, Dry Eye

Intervention / Treatment
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* Device: Tixel C
* Device: LipiFlow


Participation Criteria
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Eligibility Criteria
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Main Study (Stage1) Inclusion Criteria: Age 22 years and older of any gender or race. Provision of written informed consent prior to study participation. Willingness and ability to return for all study visits. Reports dry eye symptoms for three months prior to the study. Ocular Surface Disease Index (OSDI) score between 23-79. Tear break-up time (TBUT) <10 seconds in both eyes. Agreement/ability to abstain from dry eye/MGD medications for the time between the treatment visit/s and the final study visit. Ocular lubricants are allowed if no changes are made during the study. Reports having to use artificial tears or lubricants regulatory over the past month to relieve dry eye symptoms. Meibomian gland obstruction in both eyes based on a total Meibomian Gland Secretion Score ≤12 in each eye. At least 15 glands in each lower eyelid should be expressible, with a sterile cotton swab, at the slit lamp. Main Study (Stage1) Exclusion Criteria: History of ocular surgery including intraocular, oculo-plastic, corneal or refractive surgery within 6 months. Patient with giant papillary conjunctivitis. Patient with punctal plugs or who have had punctal cautery. Ocular injury or trauma, chemical burns, or limbal stem cell deficiency within 3 months of the baseline examination. Active ocular herpes zoster or simplex of eye or eyelid or a history of these any time. Patient who are aphakic. Cicatricial lid margin disease identified via slit lamp examination, including pemphigoid, symblepharon, etc. Active ocular infection (e.g., viral, bacterial, mycobacterial, protozoan, or fungal infection of the cornea, conjunctiva, lacrimal gland, lacrimal sac, or eyelids including a hordeolum or stye). Active ocular inflammation or history of chronic, recurrent ocular inflammation within prior 3 months (e.g., retinitis, macular inflammation, choroiditis, uveitis, iritis, scleritis, episcleritis, keratitis). Ocular surface abnormality that may compromise corneal integrity (e.g., prior chemical burn, recurrent corneal erosion, corneal epithelial defect, Grade 3 corneal fluorescein staining, or map dot fingerprint dystrophy). Lid surface abnormalities (e.g., entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis, severe ptosis) that affect lid function in either eye. Anterior blepharitis (staphylococcal, demodex or seborrheic grade 3 or 4). Systemic disease conditions that cause dry eye (e.g., Stevens-Johnson syndrome, vitamin A deficiency, rheumatoid arthritis, Wegener's granulomatosis, sarcoidosis, leukemia, Riley-Day syndrome, systemic lupus erythematosus, Sjogren's syndrome). Use of any of the following medications: Systemic medication(s) that is known to cause ocular dryness (e.g. antihistamine, diuretics, anti-hypertensives, anti-depressants, hormone therapy) whose dose of this medication(s) has not been stable within 30 days prior to enrolment. There must be no anticipated adjustments to the dose of these medications for the duration of the trial; Oral tetracyclines or azithromycin within 30 days prior to enrolment; or Topical anti-glaucoma medications within 30 days prior to enrolment. Any other systemic medication as per to the Investigator's discretion. Women in childbearing age who are pregnant, nursing, or not utilizing adequate birth control measures. Individuals using isotretinoin (Accutane) within 1 year, cyclosporine-A (Restasis) or lifitegrast ophthalmic solution (Xiidra) within 45 days prior to study treatment (day 0), or any other dry eye or MGD medications (antibiotics, non-steroidal anti-inflammatory drugs, corticosteroids) for at least 2 weeks and to maintain abstinence throughout the duration of the study (ocular lubricants are allowed if no changes are made during the study). Individuals wearing contact lenses 1 month prior study treatment (day 0), and at any point during the study. Current skin cancer, malignant sites and/or advanced premalignant lesions or moles in the treatment area. An impaired immune system condition or use of immunosuppressive medication. Collagen disorders, keloid formation and/or abnormal wound healing. Previous invasive/ablative procedures in the areas to be treated within 3 months prior to initial treatment or plans for such treatment during the course treatment, or before complete healing of such treatments has occurred. Any patient who takes or has taken any oral or topical medications, such as but not limited to topical retinoid (e.g., Retin-A), chemical peels, Latisse, Lash Boost which may cause fragile skin or impaired skin healing in the treatment area during the last 3 months and in the entire study period. Any patient who has a history of bleeding coagulopathies. Any patient who has tattoos or permanent makeup in the treated area. Any patient who has burned, blistered, irritated, or sensitive skin in any of the areas to be treated. Individuals using another ophthalmic investigational device or agent within 30 days of study participation. Any of the following dry eye treatments: Office-based dry eye treatment (e.g. IPL, LipiFlow, iLux, TearCare, Tixel, etc.) within 12 months prior to enrolment; Meibomian gland expression within 6 months prior to enrolment; Blephex or debridement within 3 months prior to enrollment is an exclusion; Punctal occlusion or punctal plug placement within 30 days prior to enrolment; Use of iTear or TrueTear device within the past 2 weeks. (Subjects must refrain from using these devices for the duration of the study.); or Any history of meibomian gland probing Use of at-home warm compresses or lid hygiene products while participating in study. IOP higher than 19 mmHg. Use of Botulinum-Toxin in the last 6 months prior to the treatment in the treatment area. Any co-existing condition, either ocular or non-ocular that, in the judgement of the investigator, could affect the safety or effectiveness of treatment or the compliance of the subject to the protocol. Study Extension (Stage 2)- Inclusion Criteria Subjects who have completed the main study CLN 0858 (stage 1) in the Tixel arm. TBUT -change from baseline in 1-month FU or 3-months FU was 2.5 seconds or above at least in one eye in the main study. Provision of written informed consent for stage 2. Agreement/ability to abstain from dry eye/MGD medications for the time in the extension study. Ocular lubricants are allowed if no changes are made during the study. Study Extension (Stage 2)-Exclusion Criteria * Same as in the main study (stage 1).

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Randomized, Masked (Evaluator), Controlled, Prospective, open label study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tixel Group<br>Screening and baseline visits, Treatment- 3 treatment sessions, followed by 2 Follow up sessions, 1and 3 months after the last treatment visit. Subject will be questioned about Discomfort and Pain Questionnaires (self-assessed) and OSDI questionnaire. | Device: Tixel C<br>* Tixel C by Novoxel®, Israel is a thermomechanical system developed for fractional treatment. The system is designed for the treatment of soft tissue by direct conduction of heat, enabling tissue coagulation combined with micro ablation with low thermal damage to the surrounding tissue.<br>|
| Active Comparator: LipiFlow<br>LipiFlow: Screening and baseline visits,Treatment session, followed by 2 Follow up sessions, 1and 3 months after the last treatment visit. Subject will be questioned about Discomfort and Pain Questionnaires (self-assessed) and OSDI questionnaire. | Device: LipiFlow<br>* Thermal pulsation (LipiFlow) consists of the localized application of heat and therapeutic pressure on the four eyelids (upper and lower) with the aim of improving drainage of the Meibomian glands.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Tear Break Up Times (TBUT) to the 4-weeks follow-up exam | Change from baseline to the 4-weeks follow-up exam in Tear Break Up Times (TBUT) | Up to 18 months include Follow up visits. | 
| Comparison of the incidence of device-related Ocular adverse events | Comparison of the incidence of device-relatedOcular adverse events for the two treatment arms | Up to 18 months include Follow up visits. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in patient OSDI | Changes from baseline in patient symptoms using Ocular Surface Disease Index (OSDI) at 4-weeks and 12-weeks follow-up exam. OSDI is assessed on a scale of 0 to 100, with higher scores representing greater disability. A patient's score between 1-12 is defined as normal, A patient's score between 13 - 22 is defined as mild, A patient's score between 23 - 32 is defined as moderate, and a patient's score between 33 - 100 is defined as severe dry eye diseases. | Up to 18 months include Follow up visits. | 
| Changes in Tear Break Up Times (TBUT) to the 12-weeks follow-up exam | Changes from baseline to the 12-weeks follow-up exam in Tear Break Up Times (TBUT) | Up to 18 months include Follow up visits. | 
| Changes in MGS to 4-weeks and 12-weeks follow-up exam | Change from baseline to 4-weeks and 12-weeks follow-up exam in Meibomian Gland Score (MGS). | Up to 18 months include Follow up visits. | 
| Safety Endpoint - Adverse events | The evaluation of discomfort and pain during treatment.(VAS score of 1-10) | Up to 18 months include Follow up visits. | 
| Ocular Surface Staining changes | Changes from baseline following treatment for the test and control devices for the Ocular Surface Staining | Up to 18 months include Follow up visits. | 
| Intraocular Pressure changes | Changes from baseline following treatment for the test and control devices for: Intraocular Pressure | Up to 18 months include Follow up visits. | 
| Best corrected distance Visual acuity changes | Changes from baseline following treatment for the test and control devices for Best corrected distance Visual acuity | Up to 18 months include Follow up visits. |