Thyroid Eye DiseasePhase 2AcTEDNCT04311606
Anti-VEGF Therapy for Acute Thyroid Eye Disease
A Phase 2 study testing Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept, Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept and Sub-tenon injection of hyaluronidase (HA) alone in people with Thyroid Eye Disease, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Eye Disease
- What is being tested?
- Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept, Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept and Sub-tenon injection of hyaluronidase (HA) alone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2020to 17 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 Humphrey Visual Field (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.
Who cannot join
- 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
Show all 18Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Anti-VEGF Therapy for Acute Thyroid Eye Disease (AcTED Study)
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.
- Conditions
- Thyroid Eye Disease
- Being tested
- Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept, Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept, Sub-tenon injection of hyaluronidase (HA) alone
- Keywords
- VEGF
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sub-tenon injection of saline followed by a sub-tenon injection of afliberceptDrug
Also called Group 1
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.
Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of afliberceptDrug
Also called Group 2
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.
Sub-tenon injection of hyaluronidase (HA) aloneDrug
Also called Group 3
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.
| Study group | Role | What they receive |
|---|---|---|
| Saline and aflibercept | Experimental | Group 1: Sub-tenon's injection of saline followed by sub-tenon injection of aflibercept Receives: Drug: Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept |
| Hyaluronidase and aflibercept | Experimental | Group 2: Sub-tenon's injection of hyaluronidase (HA) followed by sub-tenon injection of aflibercept Receives: Drug: Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept |
| Hyaluronidase alone | Placebo comparator | Group 3: Sub-tenon injection of HA injection alone Receives: Drug: Sub-tenon injection of hyaluronidase (HA) alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) Assessed as the Number of Participants in Each Group With Adverse Events.
Measured: Baseline (Day 1) to Day 45
Secondary outcomes (12)
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 Number of Participants in Each Group With Related Adverse Events.
Measured: Baseline, Day 45, and Day 90
Change in Clinical Activity as Assessed on the Clinical Activity Score (CAS)
The clinical activity score (CAS) is a seven-point scale from 0 - 7. Higher scores mean a worse outcome.
Measured: Baseline, 45 days, and 90 days
Change in Ocular Muscle Diameters as Measured by Computed Tomography (CT) Scan
Measured: Baseline, Day 45, Day 90
Change in Proptosis as Measured by Hertel Exophthalmometry
Hertel exophthalmometry measures in millimeters how much eyes bulge
Measured: Baseline, Day 45, and 90 days
Change in Proptosis as Measured by CT Scan
Measured: Baseline, Day 45, Day 90
Change in Ocular Misalignment During Physical Exam
Ocular alignment describes the how the eyes are positioned relative to each other. Ocular alignment was assessed by measurement of deviation in degrees
Measured: Baseline, Day 45, Day 90
Change in Ocular Motility as Measured as Assessed by a Scale
Ocular Motility Grade: 0=full; 1=mild restriction; 2=moderate restriction. Higher scores mean a worse outcome.
Measured: Day 0, Day 45, Day 90
Change in Vision Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA)
The ETDRS BCVA is a letter board to measure vision
Measured: Baseline, Day 45, Day 90
Change in Vision Measured by Ishihara Color Test
Ishihara color test as assessed by identification of a the letter or pattern on a plate. Eight plates in total are presented for identification. The number of plates presented below is how many out of eight plates the participants correctly identified.
Measured: Baseline, Day 45, Day 90
Change in Visual Function as Determined by Automated Humphrey Visual Field
Count of subjects with no defects in the study eye as observed in the Humphrey visual field
Measured: Day 0, Day 45, Day 90
Change in Pain/Discomfort Reported by Participants Based Upon Graves' Ophthalmopathy Quality of Life (GO-QOL) Questionnaire
Change in subjective score of pain/discomfort based upon Graves' Ophthalmopathy Quality of Life (GO-QOL) Questionnaire. The questionnaire has two subscales, each with a cumulative score: Visual Functioning Score and Appearance Score. Scores for each subscale are converted to a scale of 0-100, with higher scores mean better outcome.
Measured: Day 0, Day 45, Day 90
Change in Eyelid Retraction as Measured by the mm of Inferior and Superior Scleral Show on Physical Examination
Measured: Baseline, Day 45, Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2020
- Study start2 Nov 2020
- Primary completion17 Dec 2024
- Study completion17 Dec 2024
Why it stopped: Funding prematurely ended
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Thyroid Eye DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Principal investigator, Nahyoung Grace Lee, MD, Massachusetts Eye and Ear Infirmary
- Investigators
- Nahoung Grace Lee, MD, Principal investigator, Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04311606
- Sponsor's protocol ID
- 2019P000939
- Acronym
- AcTED
- Status last verified
- Oct 2026
- First submitted
- 12 Mar 2020
- Last updated
- 20 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participant Data will be shared at end of study, after the last participant has had his or her last visit.
Publications
Wong LL, Lee NG, Amarnani D, Choi CJ, Bielenberg DR, Freitag SK, D'Amore PA, Kim LA. Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease: An Analysis of Vascular Growth Factors with Clinical Correlation. Ophthalmology. 2016 Sep;123(9):2028-36. doi: 10.1016/j.ophtha.2016.05.052. Epub 2016 Jul 14.
PubMed 27423310Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.
PubMed 28467880Min L, Vaidya A, Becker C. Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy. Eur J Endocrinol. 2011 Feb;164(2):303-7. doi: 10.1530/EJE-10-0833. Epub 2010 Nov 18.
PubMed 21088057Kajdaniuk D, Marek B, Niedziolka-Zielonka D, Foltyn W, Nowak M, Sieminska L, Borgiel-Marek H, Glogowska-Szelag J, Ostrowska Z, Drozdz L, Kos-Kudla B. Transforming growth factor beta1 (TGFbeta1) and vascular endothelial growth factor (VEGF) in the blood of healthy people and patients with Graves' orbitopathy--a new mechanism of glucocorticoids action? Endokrynol Pol. 2014;65(5):348-56. doi: 10.5603/EP.2014.0048.
PubMed 25301484Bock F, Onderka J, Dietrich T, Bachmann B, Kruse FE, Paschke M, Zahn G, Cursiefen C. Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2545-52. doi: 10.1167/iovs.06-0570.
PubMed 17525183Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach. Br J Ophthalmol. 1989 Aug;73(8):639-44. doi: 10.1136/bjo.73.8.639.
PubMed 2765444Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, Lawitts JA, Benjamin L, Tan X, Manseau EJ, Dvorak AM, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med. 2002 Dec 2;196(11):1497-506. doi: 10.1084/jem.20021244.
PubMed 12461084Cursiefen C, Maruyama K, Jackson DG, Streilein JW, Kruse FE. Time course of angiogenesis and lymphangiogenesis after brief corneal inflammation. Cornea. 2006 May;25(4):443-7. doi: 10.1097/01.ico.0000183485.85636.ff.
PubMed 16670483
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-VEGF Therapy for Acute Thyroid Eye Disease (AcTED Study)
- ClinicalTrials.gov ID
- NCT04311606
- Acronym / sponsor ID
- AcTED / 2019P000939
- Conditions
- Thyroid Eye Disease
- Keywords
- VEGF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding prematurely ended
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Massachusetts Eye and Ear InfirmaryUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 2 Nov 2020 (actual)
- Primary completion
- 17 Dec 2024 (actual)
- Study completion
- 17 Dec 2024 (actual)
- First posted
- 17 Mar 2020 (actual)
- Results
- Posted 20 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
- 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
| Arm | Type | Receives |
|---|---|---|
| Saline and aflibercept | Experimental | Drug: Sub-tenon injection of saline followed by a sub-tenon injection of afliberceptGroup 1: Sub-tenon's injection of saline followed by sub-tenon injection of aflibercept |
| Hyaluronidase and aflibercept | Experimental | Drug: Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of afliberceptGroup 2: Sub-tenon's injection of hyaluronidase (HA) followed by sub-tenon injection of aflibercept |
| Hyaluronidase alone | Placebo comparator | Drug: Sub-tenon injection of hyaluronidase (HA) aloneGroup 3: Sub-tenon injection of HA injection alone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (18 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sub-tenon injection of saline followed by a sub-tenon injection of afliberceptAlso: Group 1The 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. | Drug | Saline and aflibercept |
| Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of afliberceptAlso: Group 2The 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. | Drug | Hyaluronidase and aflibercept |
| Sub-tenon injection of hyaluronidase (HA) aloneAlso: Group 3The 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. | Drug | Hyaluronidase alone |
Primary outcome
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) Assessed as the Number of Participants in Each Group With Adverse Events.
Time frame: Baseline (Day 1) to Day 45
12 secondary outcomes
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 Number of Participants in Each Group With Related Adverse Events.
Time frame: Baseline, Day 45, and Day 90
Change in Clinical Activity as Assessed on the Clinical Activity Score (CAS)
Time frame: Baseline, 45 days, and 90 days
Change in Ocular Muscle Diameters as Measured by Computed Tomography (CT) Scan
Time frame: Baseline, Day 45, Day 90
Change in Proptosis as Measured by Hertel Exophthalmometry
Time frame: Baseline, Day 45, and 90 days
Change in Proptosis as Measured by CT Scan
Time frame: Baseline, Day 45, Day 90
Change in Ocular Misalignment During Physical Exam
Time frame: Baseline, Day 45, Day 90
Change in Ocular Motility as Measured as Assessed by a Scale
Time frame: Day 0, Day 45, Day 90
Change in Vision Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA)
Time frame: Baseline, Day 45, Day 90
Change in Vision Measured by Ishihara Color Test
Time frame: Baseline, Day 45, Day 90
Change in Visual Function as Determined by Automated Humphrey Visual Field
Time frame: Day 0, Day 45, Day 90
Change in Pain/Discomfort Reported by Participants Based Upon Graves' Ophthalmopathy Quality of Life (GO-QOL) Questionnaire
Time frame: Day 0, Day 45, Day 90
Change in Eyelid Retraction as Measured by the mm of Inferior and Superior Scleral Show on Physical Examination
Time frame: Baseline, Day 45, Day 90
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27423310Wong LL, Lee NG, Amarnani D, Choi CJ, Bielenberg DR, Freitag SK, D'Amore PA, Kim LA. Orbital Angiogenesis and Lymphangiogenesis in Thyroid Eye Disease: An Analysis of Vascular Growth Factors with Clinical Correlation. Ophthalmology. 2016 Sep;123(9):2028-36. doi: 10.1016/j.ophtha.2016.05.052. Epub 2016 Jul 14.
- Background: PubMed 28467880Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, Harris GJ, Antonelli A, Salvi M, Goldberg RA, Gigantelli JW, Couch SM, Shriver EM, Hayek BR, Hink EM, Woodward RM, Gabriel K, Magni G, Douglas RS. Teprotumumab for Thyroid-Associated Ophthalmopathy. N Engl J Med. 2017 May 4;376(18):1748-1761. doi: 10.1056/NEJMoa1614949.
- Background: PubMed 21088057Min L, Vaidya A, Becker C. Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy. Eur J Endocrinol. 2011 Feb;164(2):303-7. doi: 10.1530/EJE-10-0833. Epub 2010 Nov 18.
- Background: PubMed 25301484Kajdaniuk D, Marek B, Niedziolka-Zielonka D, Foltyn W, Nowak M, Sieminska L, Borgiel-Marek H, Glogowska-Szelag J, Ostrowska Z, Drozdz L, Kos-Kudla B. Transforming growth factor beta1 (TGFbeta1) and vascular endothelial growth factor (VEGF) in the blood of healthy people and patients with Graves' orbitopathy--a new mechanism of glucocorticoids action? Endokrynol Pol. 2014;65(5):348-56. doi: 10.5603/EP.2014.0048.
- Background: PubMed 17525183Bock F, Onderka J, Dietrich T, Bachmann B, Kruse FE, Paschke M, Zahn G, Cursiefen C. Bevacizumab as a potent inhibitor of inflammatory corneal angiogenesis and lymphangiogenesis. Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2545-52. doi: 10.1167/iovs.06-0570.
- Background: PubMed 2765444Mourits MP, Koornneef L, Wiersinga WM, Prummel MF, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves' ophthalmopathy: a novel approach. Br J Ophthalmol. 1989 Aug;73(8):639-44. doi: 10.1136/bjo.73.8.639.
- Background: PubMed 12461084Nagy JA, Vasile E, Feng D, Sundberg C, Brown LF, Detmar MJ, Lawitts JA, Benjamin L, Tan X, Manseau EJ, Dvorak AM, Dvorak HF. Vascular permeability factor/vascular endothelial growth factor induces lymphangiogenesis as well as angiogenesis. J Exp Med. 2002 Dec 2;196(11):1497-506. doi: 10.1084/jem.20021244.
- Background: PubMed 16670483Cursiefen C, Maruyama K, Jackson DG, Streilein JW, Kruse FE. Time course of angiogenesis and lymphangiogenesis after brief corneal inflammation. Cornea. 2006 May;25(4):443-7. doi: 10.1097/01.ico.0000183485.85636.ff.
- Individual participant dataSharing planned: Yes. Participant Data will be shared at end of study, after the last participant has had his or her last visit.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nahoung Grace Lee, MD principal investigator
Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept, Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept and Sub-tenon injection of hyaluronidase (HA) alone in people with Thyroid Eye Disease, run by Massachusetts Eye and Ear Infirmary at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) Assessed as the Number of Participants in Each Group With Adverse Events. (time frame: Baseline (Day 1) to Day 45). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04311606, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026.