Intravitreal Adalimumab Versus Subcutaneous Adalimumab in Non-infectious Uveitis

NCT02706704 | Recruiting Phase 2 DMC

• 1 other identifier: OPH.RH.07
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Uveitis; Non-Infectious Uveitis

Keywords

Intravitreal Adalimumab; Subcutaneous Adalimumab

Outcome Measures

Primary Outcomes (2)

• Vitreous Haze

  Change in Vitreous Haze grade in each eye \[National Eye Institute (NEI)/ Standardization of Uveitis Nomenclature (SUN) criteria\]

  26 Weeks

• Anterior Chamber Cells

  Change in Anterior Chamber (AC) cell grade in each eye.

  26 Weeks

Secondary Outcomes (4)

• Visual Acuity

  26 Weeks

• Macular Edema

  26 Weeks

• Angiography Score

  26 Weeks

• Steroids Tapering

  26 Weeks

Study Arms (2)

Intravitreal

ACTIVE COMPARATOR

Intravitreal injection of 1.5mg/0.03ml adalimumab given at zero, 2 weeks, and then every 4 weeks.

Drug: Adalimumab

Systemic

ACTIVE COMPARATOR

Subcutaneous injection of 40 mg adalimumab (Humira) given every 2 weeks.

Drug: Adalimumab

Interventions

Adalimumab DRUG

Intravitreal; Systemic

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• American University of Beirut Medical Center: lead

Study Sites (1)

American University of Beirut Medical Center

Beirut, Lebanon

RECRUITING

Related Publications (11)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Manzano RP, Peyman GA, Carvounis PE, Damico FM, Aguiar RG, Ioshimoto GL, Ventura DF, Cursino ST, Takahashi W. Toxicity of high-dose intravitreal adalimumab (Humira) in the rabbit. J Ocul Pharmacol Ther. 2011 Aug;27(4):327-31. doi: 10.1089/jop.2010.0174. Epub 2011 Jun 13.

  PMID: 21668348 BACKGROUND

• Tsilimbaris M, Diakonis VF, Naoumidi I, Charisis S, Kritikos I, Chatzithanasis G, Papadaki T, Plainis S. Evaluation of potential retinal toxicity of adalimumab (Humira). Graefes Arch Clin Exp Ophthalmol. 2009 Aug;247(8):1119-25. doi: 10.1007/s00417-009-1065-y. Epub 2009 Mar 19.

  PMID: 19296122 BACKGROUND

• Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057.

  PMID: 16196117 BACKGROUND

MeSH Terms

Conditions

Uveitis

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Rola N Hamam, MD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rola N Hamam, MD

CONTACT

+961-1-350000; rh46@aub.edu.lb

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2016
• First Posted: March 11, 2016
• Study Start: February 1, 2016
• Primary Completion: December 1, 2025
• Study Completion: February 1, 2026
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)