Anti-VEGF Therapy for Acute Thyroid Eye Disease

Study Overview
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Brief Summary
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The primary objective of this clinical trial is to assess the safety and tolerability of sub-tenon aflibercept in combination with either saline or hyaluronidase (HA) in patients with acute Thyroid Eye Disease (TED) as assessed by the incidence and severity of adverse events from baseline to day 45. Participants will undergo clinical examinations and receive three injections of aflibercept with saline, aflibercept with hyaluronidase, or hyaluronidase.

Official Title
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Anti-VEGF Therapy for Acute Thyroid Eye Disease (AcTED Study)

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept
* Drug: Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept
* Drug: Sub-tenon injection of hyaluronidase (HA) alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum of 18 years-old Active Thyroid Eye Disease Clinical Activity Score (CAS) between 3 and 5, inclusive Phakic and pseudophakic eyes are allowed in the study. Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures Willing and able to comply with clinic visits and study-related procedures Only one eye will be enrolled. The worse eye (demonstrating any of these features: worse HVF results, worse restricted motility, worse visual acuity, worse edema, worse proptosis, worse eyelid retraction) will be enrolled. If both eyes are equivalent, we will enroll the non-dominant eye. Exclusion Criteria: History of orbital, strabismus, or eyelid surgery or orbital radiation Optic neuropathy or other vision-threatening signs Patients currently on systemic or topical steroids. If they received steroids in the past, they would require a 6 week washout period and the cumulative dose of steroids must be less than 1 gram of methylprednisolone (or equivalent). During the washout period we will contact patients by phone weekly to monitor their safety and address any concerns they may have related to no longer taking steroids . Patients who have taken teprotumumab (Tepezza.) Patients who have received intraocular anti-VEGF medications within 1 year of screening Patients who have a history of receiving systemic anti-VEGF Presence of other retinal vascular diseases (diabetic retinopathy, vein occlusion) that could affect the VEGF levels within the eye History of stroke or prior myocardial infarction Known hypersensitivity to aflibercept Infectious conjunctivitis, keratitis, or endophthalmitis of either eye Presence of a glaucoma shunting or filtration device that is subconjunctival Previous participation in any studies of investigational drugs within 1 month preceding Day 0 Any clinically significant acute or chronic medical condition that would preclude participation in a clinical study Pregnant or breast-feeding women Sexually active men* or women of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly) History of hyaluronidase (HA) injection after the diagnosis of thyroid eye disease Taking part in other research studies in the past 12 months that have involved radiation exposure Participated in other research studies in the past 12 months that required radiologic imaging (particularly CT scans and not MRIs)

Ages Eligible for Study
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Minimum Age: 18 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: Three groups as follows: Group 1: Sub-tenon's injection of saline followed by sub-tenon injection of aflibercept Group 2: Sub-tenon's injection of hyaluronidase (HA) followed by sub-tenon injection of aflibercept; and Group 3: Sub-tenon injection of HA injection alone
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Saline and aflibercept<br>Group 1: Sub-tenon's injection of saline followed by sub-tenon injection of aflibercept | Drug: Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept<br>* The study will randomly assign a total of eight subjects into this treatment arm to receive a sub-tenon injection of saline followed by injection of 4 mg aflibercept (total volume 1.1 ml) in the worse eye. Injections will be given three times: on day 1, day 14 and day 28. Subjects will be followed until day 90.<br>* Other names: Group 1;|
| Experimental: Hyaluronidase and aflibercept<br>Group 2: Sub-tenon's injection of hyaluronidase (HA) followed by sub-tenon injection of aflibercept | Drug: Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept<br>* The study will randomly assign a total of eight subjects into this treatment arm to receive a sub-tenon injection of hyaluronidase (HA) followed by injection of 4 mg aflibercept (total volume 1.1 ml) in the worse eye. Injections will be given three times: on day 1, day 14 and day 28. Subjects will be followed until day 90.<br>* Other names: Group 2;|
| Placebo Comparator: Hyaluronidase alone<br>Group 3: Sub-tenon injection of HA injection alone | Drug: Sub-tenon injection of hyaluronidase (HA) alone<br>* The study will randomly assign a total of eight subjects into this treatment arm to receive a sub-tenon injection of hyaluronidase (HA) injection alone (total volume 1.1 ml) in the worse eye. Injections will be given three times: on day 1, day 14 and day 28. Subjects will be followed until day 90.<br>* Other names: Group 3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome: Safety | To assess the safety and tolerability of sub-tenon aflibercept in combination with either saline or hyaluronidase (HA) in patients with acute Thyroid Eye Disease (TED) as assessed by the incidence and severity of adverse events | 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome: Safety | To assess the safety and tolerability of sub-tenon aflibercept in combination with either saline or hyaluronidase (HA) in patients with acute Thyroid Eye Disease (TED) as assessed by the incidence and severity of adverse events | Baseline to day 90 | 
| Secondary Outcome: Change in Clinical Activity | Change in clinical activity as measured by a 2 point decrease on the clinical activity score (CAS) | 1-90 days | 
| Secondary Outcome: Change in Ocular Muscle | Change in extra ocular muscle diameter as measured by computed tomography (CT) scan | 1-90 days | 
| Secondary Outcome: Change in Proptosis measured by exophthalmometry | Change in proptosis as measured by Hertel exophthalmometry | 1-90 days | 
| Secondary Outcome: Change in Proptosis by CT scan | Change in proptosis as measured by CT scan | 1-90 days | 
| Secondary Outcome: Change in Ocular Alignment | Change in degree of ocular misalignment during physical exam | 1-90 days | 
| Secondary Outcome: Change in Ocular Motility | Change in limitation in ocular motility as measured with physical examination | 1-90 days | 
| Secondary Outcome: Change in Vision measured by ETDRS BCVA | Change in vision as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA) | 1-90 days | 
| Secondary Outcome: Change in Vision measured by Ishihara color test | Change in vision as measured by Ishihara color test | 1-90 days | 
| Secondary Outcome: Change in Visual Function | Change in visual function as determined by automated Humphrey visual field | 1-90 days | 
| Secondary Outcome: Change in Pain/Discomfort Reported by Subjects | Change in subjective score of pain/discomfort based upon patient Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire | 1-90 days | 
| Secondary Outcome: Change in Eyelid Retraction/Position | Change in eyelid retraction/position as measured by the mm of inferior and superior scleral show on physical examination | 1-90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGF