Ignite Creation Date:
2025-12-26 @ 5:17 PM
Ignite Modification Date:
2025-12-29 @ 1:15 AM
Study NCT ID:
NCT04311606
Status:
RECRUITING
Last Update Posted:
2023-03-20
First Post:
2020-03-12
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Anti-VEGF Therapy for Acute Thyroid Eye Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D049970', 'term': 'Graves Ophthalmopathy'}], 'ancestors': [{'id': 'D015785', 'term': 'Eye Diseases, Hereditary'}, {'id': 'D005128', 'term': 'Eye Diseases'}, {'id': 'D006111', 'term': 'Graves Disease'}, {'id': 'D005094', 'term': 'Exophthalmos'}, {'id': 'D009916', 'term': 'Orbital Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D006042', 'term': 'Goiter'}, {'id': 'D013959', 'term': 'Thyroid Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D006980', 'term': 'Hyperthyroidism'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D012847', 'term': 'Single Person'}], 'ancestors': [{'id': 'D017533', 'term': 'Marital Status'}, {'id': 'D005191', 'term': 'Family Characteristics'}, {'id': 'D003710', 'term': 'Demography'}, {'id': 'D011154', 'term': 'Population Characteristics'}, {'id': 'D012959', 'term': 'Socioeconomic Factors'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER'], 'maskingDescription': 'Double-masked'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': "Three groups as follows:\n\nGroup 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"}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 24}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2020-11-02', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-02', 'completionDateStruct': {'date': '2027-01-01', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-03-16', 'studyFirstSubmitDate': '2020-03-12', 'studyFirstSubmitQcDate': '2020-03-16', 'lastUpdatePostDateStruct': {'date': '2023-03-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-03-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2025-09-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Primary Outcome: Safety', 'timeFrame': '45 days', 'description': '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'}], 'secondaryOutcomes': [{'measure': 'Secondary Outcome: Safety', 'timeFrame': 'Baseline to day 90', 'description': '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'}, {'measure': 'Secondary Outcome: Change in Clinical Activity', 'timeFrame': '1-90 days', 'description': 'Change in clinical activity as measured by a 2 point decrease on the clinical activity score (CAS)'}, {'measure': 'Secondary Outcome: Change in Ocular Muscle', 'timeFrame': '1-90 days', 'description': 'Change in extra ocular muscle diameter as measured by computed tomography (CT) scan'}, {'measure': 'Secondary Outcome: Change in Proptosis measured by exophthalmometry', 'timeFrame': '1-90 days', 'description': 'Change in proptosis as measured by Hertel exophthalmometry'}, {'measure': 'Secondary Outcome: Change in Proptosis by CT scan', 'timeFrame': '1-90 days', 'description': 'Change in proptosis as measured by CT scan'}, {'measure': 'Secondary Outcome: Change in Ocular Alignment', 'timeFrame': '1-90 days', 'description': 'Change in degree of ocular misalignment during physical exam'}, {'measure': 'Secondary Outcome: Change in Ocular Motility', 'timeFrame': '1-90 days', 'description': 'Change in limitation in ocular motility as measured with physical examination'}, {'measure': 'Secondary Outcome: Change in Vision measured by ETDRS BCVA', 'timeFrame': '1-90 days', 'description': 'Change in vision as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) Best Corrected Visual Acuity (BCVA)'}, {'measure': 'Secondary Outcome: Change in Vision measured by Ishihara color test', 'timeFrame': '1-90 days', 'description': 'Change in vision as measured by Ishihara color test'}, {'measure': 'Secondary Outcome: Change in Visual Function', 'timeFrame': '1-90 days', 'description': 'Change in visual function as determined by automated Humphrey visual field'}, {'measure': 'Secondary Outcome: Change in Pain/Discomfort Reported by Subjects', 'timeFrame': '1-90 days', 'description': "Change in subjective score of pain/discomfort based upon patient Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire"}, {'measure': 'Secondary Outcome: Change in Eyelid Retraction/Position', 'timeFrame': '1-90 days', 'description': 'Change in eyelid retraction/position as measured by the mm of inferior and superior scleral show on physical examination'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['VEGF'], 'conditions': ['Thyroid Eye Disease']}, 'referencesModule': {'references': [{'pmid': '27423310', 'type': 'BACKGROUND', '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."}, {'pmid': '28467880', 'type': 'BACKGROUND', '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.'}, {'pmid': '21088057', 'type': 'BACKGROUND', '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.'}, {'pmid': '25301484', 'type': 'BACKGROUND', '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."}, {'pmid': '17525183', 'type': 'BACKGROUND', 'citation': '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.'}, {'pmid': '2765444', 'type': 'BACKGROUND', '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."}, {'pmid': '12461084', 'type': 'BACKGROUND', '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.'}, {'pmid': '16670483', 'type': 'BACKGROUND', '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nParticipants will undergo clinical examinations and receive three injections of aflibercept with saline, aflibercept with hyaluronidase, or hyaluronidase.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Minimum of 18 years-old\n2. Active Thyroid Eye Disease\n3. Clinical Activity Score (CAS) between 3 and 5, inclusive\n4. Phakic and pseudophakic eyes are allowed in the study.\n5. Willing and able to provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures\n6. Willing and able to comply with clinic visits and study-related procedures\n7. Only one eye will be enrolled. The worse eye (demonstrating any of these features:\n\nworse 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.\n\nExclusion Criteria:\n\n1. History of orbital, strabismus, or eyelid surgery or orbital radiation\n2. Optic neuropathy or other vision-threatening signs\n3. 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 .\n4. Patients who have taken teprotumumab (Tepezza.)\n5. Patients who have received intraocular anti-VEGF medications within 1 year of screening\n6. Patients who have a history of receiving systemic anti-VEGF\n7. Presence of other retinal vascular diseases (diabetic retinopathy, vein occlusion) that could affect the VEGF levels within the eye\n8. History of stroke or prior myocardial infarction\n9. Known hypersensitivity to aflibercept\n10. Infectious conjunctivitis, keratitis, or endophthalmitis of either eye\n11. Presence of a glaucoma shunting or filtration device that is subconjunctival\n12. Previous participation in any studies of investigational drugs within 1 month preceding Day 0\n13. Any clinically significant acute or chronic medical condition that would preclude participation in a clinical study\n14. Pregnant or breast-feeding women\n15. 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)\n16. History of hyaluronidase (HA) injection after the diagnosis of thyroid eye disease\n17. Taking part in other research studies in the past 12 months that have involved radiation exposure\n18. Participated in other research studies in the past 12 months that required radiologic imaging (particularly CT scans and not MRIs)'}, 'identificationModule': {'nctId': 'NCT04311606', 'acronym': 'AcTED', 'briefTitle': 'Anti-VEGF Therapy for Acute Thyroid Eye Disease', 'organization': {'class': 'OTHER', 'fullName': 'Massachusetts Eye and Ear Infirmary'}, 'officialTitle': 'Anti-VEGF Therapy for Acute Thyroid Eye Disease (AcTED Study)', 'orgStudyIdInfo': {'id': '2019P000939'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Saline and aflibercept', 'description': "Group 1: Sub-tenon's injection of saline followed by sub-tenon injection of aflibercept", 'interventionNames': ['Drug: Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept']}, {'type': 'EXPERIMENTAL', 'label': 'Hyaluronidase and aflibercept', 'description': "Group 2: Sub-tenon's injection of hyaluronidase (HA) followed by sub-tenon injection of aflibercept", 'interventionNames': ['Drug: Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Hyaluronidase alone', 'description': 'Group 3: Sub-tenon injection of HA injection alone', 'interventionNames': ['Drug: Sub-tenon injection of hyaluronidase (HA) alone']}], 'interventions': [{'name': 'Sub-tenon injection of saline followed by a sub-tenon injection of aflibercept', 'type': 'DRUG', 'otherNames': ['Group 1'], 'description': '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.', 'armGroupLabels': ['Saline and aflibercept']}, {'name': 'Sub-tenon injection of hyaluronidase (HA) followed by a sub-tenon injection of aflibercept', 'type': 'DRUG', 'otherNames': ['Group 2'], 'description': '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.', 'armGroupLabels': ['Hyaluronidase and aflibercept']}, {'name': 'Sub-tenon injection of hyaluronidase (HA) alone', 'type': 'DRUG', 'otherNames': ['Group 3'], 'description': '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.', 'armGroupLabels': ['Hyaluronidase alone']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Stacey M Ellender, PhD', 'role': 'CONTACT', 'phone': '617-573-6060'}, {'name': 'Carolina Chiou, MD', 'role': 'SUB_INVESTIGATOR'}, {'name': 'Jonathan Lu, MD', 'role': 'SUB_INVESTIGATOR'}], 'facility': 'Mass Eye and Ear', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'centralContacts': [{'name': 'Nahoung Grace Lee, MD', 'role': 'CONTACT', 'email': 'Grace_Lee@MEEI.HARVARD.EDU', 'phone': '617-572-5550'}, {'name': 'Yuki A Wiland, BS', 'role': 'CONTACT', 'email': 'yuki_wiland@meei.harvard.edu', 'phone': '617-573-6060'}], 'overallOfficials': [{'name': 'Nahoung Grace Lee, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Investigator'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'SAP'], 'timeFrame': 'January 2026', 'ipdSharing': 'YES', 'description': 'Participant Data will be shared at end of study, after the last participant has had his or her last visit.', 'accessCriteria': 'Email Request to PI'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Massachusetts Eye and Ear Infirmary', 'class': 'OTHER'}, 'collaborators': [{'name': 'Regeneron Pharmaceuticals', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Physician', 'investigatorFullName': 'Nahyoung Grace Lee, MD', 'investigatorAffiliation': 'Massachusetts Eye and Ear Infirmary'}}}}