Anti-VEGF Therapy for Acute Thyroid Eye Disease

Thyroid Eye Disease Clinical Trial

— AcTED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04311606
• Other study ID #: 2019P000939
• Status: Recruiting
• Phase: Phase 2
• Start date: November 2, 2020
• Est. completion date: January 1, 2027

Study information

• Verified date: February 2023
• Source: Massachusetts Eye and Ear Infirmary
• Contact: Nahoung Grace Lee, MD
• Phone: 617-572-5550
• Email: Grace_Lee[@]MEEI.HARVARD.EDU
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Participants will undergo clinical examinations and receive three injections of aflibercept with saline, aflibercept with hyaluronidase, or hyaluronidase.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: January 1, 2027
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy
• Thyroid Diseases
• Thyroid Eye Disease

Intervention

Drug:
• Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept
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 aflibercept
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) alone
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.

Locations

Country	Name	City	State
United States	Mass Eye and Ear	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts Eye and Ear Infirmary	Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (8)

Bock 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. — View Citation

Cursiefen 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. — View Citation

Kajdaniuk 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. — View Citation

Min 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. — View Citation

Mourits 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. — View Citation

Nagy 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. — View Citation

Smith 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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	Secondary Outcome: Change in Ocular Muscle	Change in extra ocular muscle diameter as measured by computed tomography (CT) scan	1-90 days
Secondary	Secondary Outcome: Change in Proptosis measured by exophthalmometry	Change in proptosis as measured by Hertel exophthalmometry	1-90 days
Secondary	Secondary Outcome: Change in Proptosis by CT scan	Change in proptosis as measured by CT scan	1-90 days
Secondary	Secondary Outcome: Change in Ocular Alignment	Change in degree of ocular misalignment during physical exam	1-90 days
Secondary	Secondary Outcome: Change in Ocular Motility	Change in limitation in ocular motility as measured with physical examination	1-90 days
Secondary	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	Secondary Outcome: Change in Vision measured by Ishihara color test	Change in vision as measured by Ishihara color test	1-90 days
Secondary	Secondary Outcome: Change in Visual Function	Change in visual function as determined by automated Humphrey visual field	1-90 days
Secondary	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	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