Clinical trial NCT02706704: Intravitreal Adalimumab Versus Subcutaneous Adalimumab in Non-infectious Uveitis
Official title: Efficacy of Intravitreal Adalimumab Compared to Subcutaneous Adalimumab in Patients With Non-infectious Uveitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Uveitis
Non-Infectious Uveitis
Keywords: Intravitreal Adalimumab
Subcutaneous Adalimumab
Lead sponsor: American University of Beirut Medical Center
Sponsor class: OTHER
First posted: 2016-03-11
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Vitreous Haze
timeFrame: 26 Weeks
measure: Anterior Chamber Cells
timeFrame: 26 Weeks
Secondary outcomes:
measure: Visual Acuity
timeFrame: 26 Weeks
measure: Macular Edema
timeFrame: 26 Weeks
measure: Angiography Score
timeFrame: 26 Weeks
measure: Steroids Tapering
timeFrame: 26 Weeks
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: American University of Beirut Medical Center
Study officials:
affiliation: American University of Beirut Medical Center
name: Rola N Hamam, MD
role: PRINCIPAL_INVESTIGATOR
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