Intravitreal Adalimumab Versus Subcutaneous Adalimumab in Non-infectious Uveitis

Официальное название

Efficacy of Intravitreal Adalimumab Compared to Subcutaneous Adalimumab in Patients With Non-infectious Uveitis

Обзор

The objective of this study is to compare and evaluate the efficacy of subcutaneous (40mg) adalimumab biweekly injections to intravitreal adalimumab (1.5 mg/ 0.03 mL) administration, given at zero, 2 weeks then every four weeks, in subjects with active non-infectious intermediate-, posterior-, or pan-uveitis.

Подробное описание

Subject groups:

32 subjects will be enrolled in this study, 16 in each arm. They will be randomized to receive either 1.5 mg/ 0.03 mL of adalimumab by intravitreal injection or 40 mg of adalimumab subcutaneously at their first treatment visit and at the 2 weeks visit if eligible for a repeat injection. Follow up will be every 2 days the first week then one week later and after that every 4-week intervals for total of 26 weeks.

Intervention Details:

* Systemic adalimumab: Subcutaneous injection of 40 mg adalimumab (Humira) given every 2 weeks. * Local adalimumab: Intravitreal injection of 1.5mg/0.03ml adalimumab given at zero, 2 weeks, and then every 4 weeks.

Pre-treatment work up

Patients will undergo a comprehensive eye exam:

* Visual acuity, slit-lamp examination of the anterior segment, dilated fundus examination, electroretinography (ERG) and fluorescein angiography (FA). * Central macular thickness of all eyes will be measured with ocular coherence tomography before treatment. * Purified Protein Derivative (PPD), Complete blood count (CBC) and SGPT.

Post-injection follow-up

* Patients will be followed up every 2 days during the first week then one week later and after that every 4-week intervals. * On follow up visits, if deterioration in vision of two or more ETDRS lines or worsening of ocular inflammation by more than 1+ cells/haze is detected at any visit, patients will be removed from the study and receive appropriate treatment. Otherwise, if vision was stable or improved and/or inflammation is same or better, patients will be re-injected. * Follow up is for 26 weeks. * OCT and fluorescein angiography each visit. * ERG will be performed at baseline and 26 weeks. * Blood studies (CBC and SGPT) will be performed at baseline, 14 weeks and at 26 weeks. * Injections would be delayed if a patient has an acute infection and would be given when it subsides.

Вмешательства

• Препарат Adalimumab

Первичные конечные точки

• Vitreous Haze [Срок оценки: 26 Weeks]
• Anterior Chamber Cells [Срок оценки: 26 Weeks]

Вторичные конечные точки (4)

• Visual Acuity [Срок оценки: 26 Weeks]
• Macular Edema [Срок оценки: 26 Weeks]
• Angiography Score [Срок оценки: 26 Weeks]
• Steroids Tapering [Срок оценки: 26 Weeks]

Критерии участия

Критерии включения

• Subject is ≥ 18 years of age.
• Subject is diagnosed with non-infectious intermediate-, posterior-, or pan-uveitis.
• Subject must have active disease at baseline as defined by the presence of at least 1 of the following parameters in at least one eye despite at least 2 weeks of prednisone ≥ 10 mg/day (or oral corticosteroid equivalent):

• Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
• ≥ 1+ anterior chamber cells (Standardization of Uveitis Nomenclature \[SUN\] criteria)
• ≥ 1+ vitreous haze (National Eye Institute \[NEI\]/SUN criteria)
• Subject with documented prior adequate response to oral corticosteroids (equivalent of oral prednisone up to 1 mg/kg/day).
• If subject is on prednisone >=10 mg (or corticosteroid equivalent) at baseline, the dose has not been increased or decreased in the past 14 days.
• No increase in the immune modulatory therapy in the past three months
• Negative PPD test.
• Positive PPD test on anti Tb medications.

Критерии исключения

• Subject with isolated anterior uveitis.
• Subject with confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus, lyme disease, toxoplasmosis and herpes simplex virus (HSV).
• Subject with serpiginous choroidopathy.
• Subject with corneal or lens opacity that precludes visualization of the fundus or that likely requires cataract surgery during the duration of the trial.
• Subject with corneal or lens opacities that preclude the evaluation of the vitreous haze.
• Subject with uncontrolled high intraocular pressure of ≥ 25 mmHg on maximal therapy.
• Subject with intermediate uveitis and symptoms and/or MRI findings suggestive of a demyelinating disease such as multiple sclerosis. All subjects with intermediate uveitis must have had a prior brain MRI at time of or after diagnosis of intermediate uveitis.
• Subject has received glucocorticosteroids implant (Retisert®), or Ozurdex within 6 months prior to baseline visit.
• Subject has received intraocular or periocular corticosteroids or intravitreal methotrexate within 90 days prior to Baseline visit.
• Subject with proliferative or severe non-proliferative diabetic retinopathy.
• Subject with neovascular/wet age-related macular degeneration
• Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) with the potential for macular structural damage independent of the inflammatory process.
• Subject with a systemic inflammatory disease and requires additional therapy with a systemic immunosuppressive agent at the time of study entry.
• Subjects with history of active or latent Mycobacterium tuberculosis documented by Purified Protein Derivative (PPD) and chest X-ray and not anti tuberculosis (TB) treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Ливан · 1 центр

• American University of Beirut Medical Center — Beirut

Публикации

• Hamam RN, Barikian AW, Antonios RS, Abdulaal MR, Alameddine RM, El Mollayess G, Mansour AM. Intravitreal Adalimumab in Active Noninfectious Uveitis: A Pilot Study. Ocul Immunol Inflamm. 2016 Jun;24(3):319-26. doi: 10.3109/09273948.2014.990041. Epub 2014 Dec 30. PMID 25549063
• Santos Lacomba M, Marcos Martin C, Gallardo Galera JM, Gomez Vidal MA, Collantes Estevez E, Ramirez Chamond R, Omar M. Aqueous humor and serum tumor necrosis factor-alpha in clinical uveitis. Ophthalmic Res. 2001 Sep-Oct;33(5):251-5. doi: 10.1159/000055677. PMID 11586057
• Perez-Guijo V, Santos-Lacomba M, Sanchez-Hernandez M, Castro-Villegas Mdel C, Gallardo-Galera JM, Collantes-Estevez E. Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27. Curr Med Res Opin. 2004;20(2):155-7. doi: 10.1185/030079903125002847. PMID 15006008
• Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S, Kupper H. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis. 2009 May;68(5):696-701. doi: 10.1136/ard.2008.092585. Epub 2008 Jul 28. PMID 18662932
• Mansour AM. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007 Mar;91(3):274-6. doi: 10.1136/bjo.2006.108050. PMID 17322463
• Diaz-Llopis M, Garcia-Delpech S, Salom D, Udaondo P, Hernandez-Garfella M, Bosch-Morell F, Quijada A, Romero FJ. Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther. 2008 Jun;24(3):351-61. doi: 10.1089/jop.2007.0104. PMID 18476805
• Wu L, Hernandez-Bogantes E, Roca JA, Arevalo JF, Barraza K, Lasave AF. intravitreal tumor necrosis factor inhibitors in the treatment of refractory diabetic macular edema: a pilot study from the Pan-American Collaborative Retina Study Group. Retina. 2011 Feb;31(2):298-303. doi: 10.1097/IAE.0b013e3181eac7a6. PMID 21099452
• Androudi S, Tsironi E, Kalogeropoulos C, Theodoridou A, Brazitikos P. Intravitreal adalimumab for refractory uveitis-related macular edema. Ophthalmology. 2010 Aug;117(8):1612-6. doi: 10.1016/j.ophtha.2009.12.011. Epub 2010 Apr 8. PMID 20378179

Идентификаторы

NCT: NCT02706704 · OPH.RH.07

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗