Clinical trial NCT04311606: Anti-VEGF Therapy for Acute Thyroid Eye Disease
Official title: Anti-VEGF Therapy for Acute Thyroid Eye Disease (AcTED Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Thyroid Eye Disease
Keywords: VEGF
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-03-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Minimum of 18 years-old
2. Active Thyroid Eye Disease
3. Clinical Activity Score (CAS) between 3 and 5, inclusive
4. Phakic and pseudophakic eyes are allowed in the study.
5. Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures
6. Willing and able to comply with clinic visits and study-related procedures
7. 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:

1. History of orbital, strabismus, or eyelid surgery or orbital radiation
2. Optic neuropathy or other vision-threatening signs
3. 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 .
4. Patients who have taken teprotumumab (Tepezza.)
5. Patients who have received intraocular anti-VEGF medications within 1 year of screening
6. Patients who have a history of receiving systemic anti-VEGF
7. Presence of other retinal vascular diseases (diabetic retinopathy, vein occlusion) that could affect the VEGF levels within the eye
8. History of stroke or prior myocardial infarction
9. Known hypersensitivity to aflibercept
10. Infectious conjunctivitis, keratitis, or endophthalmitis of either eye
11. Presence of a glaucoma shunting or filtration device that is subconjunctival
12. Previous participation in any studies of investigational drugs within 1 month preceding Day 0
13. Any clinically significant acute or chronic medical condition that would preclude participation in a clinical study
14. Pregnant or breast-feeding women
15. 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)
16. History of hyaluronidase (HA) injection after the diagnosis of thyroid eye disease
17. Taking part in other research studies in the past 12 months that have involved radiation exposure
18. Participated in other research studies in the past 12 months that required radiologic imaging (particularly CT scans and not MRIs)

Primary outcomes:
measure: Primary Outcome: Safety
timeFrame: 45 days
Secondary outcomes:
measure: Secondary Outcome: Safety
timeFrame: Baseline to day 90
measure: Secondary Outcome: Change in Clinical Activity
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Ocular Muscle
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Proptosis measured by exophthalmometry
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Proptosis by CT scan
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Ocular Alignment
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Ocular Motility
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Vision measured by ETDRS BCVA
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Vision measured by Ishihara color test
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Visual Function
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Pain/Discomfort Reported by Subjects
timeFrame: 1-90 days
measure: Secondary Outcome: Change in Eyelid Retraction/Position
timeFrame: 1-90 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Mass Eye and Ear
state: Massachusetts
Study officials:
affiliation: Investigator
name: Nahoung Grace Lee, MD
role: PRINCIPAL_INVESTIGATOR
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