Clinical trial NCT02769702: Open Label Study of Acthar SQ Gel Injection in Patients With Active Anterior Uveitis
Official title: Prospective Open Label Study of Acthar SQ Gel Injection in Patients With Active Anterior Uveitis Who Are Not Well Controlled With, or Intolerant of, Topical or Systemic Corticosteroids
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Uveitis
Keywords: Uveitis
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Mallinckrodt
First posted: 2016-05-12
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Uveitis is an acute or chronic inflammatory condition of unknown etiology. Although uveitis often responds adequately to topical corticosteroids, there are many patients for which this treatment is either inadequate or not tolerated. A patient with inadequate response to treatment would manifest uveitis activity by slit lamp examination determination of anterior chamber cellularity. Lack of tolerance of therapy commonly manifests as ocular hypertension (greater than 21 mmHg measured by tonometry)complicating chronic topical corticosteroid administration, leading to glaucoma and permanent visual loss. Moreover, systemic corticosteroids may be required at a dose unsafe for chronic administration. In these situations, an immunosuppressive medication is often added as a "steroid-sparing" agent. If and when there is clinical response to the added immunosuppressive, the oral and/or topical corticosteroid dose can be reduced or eliminated to avoid toxicity.

There are several reasons for believing that Acthar might be beneficial in the treatment of uveitis patients. In addition to increasing adrenal production or cortisol, Acthar has another important mechanisms of action mediated by its binding of melanocortin receptors. Melanocortin down-regulates activity of B and T lymphocytes, monocytes and macrophages. In animal studies, melanocortin peptides down-regulate T helper cells, up-regulate T Regulatory cells, and decrease B lymphocyte production of B Lymphocyte Stimulator. In macrophages, there is down-regulation of IL-1, IL-2, INF gamma, TNF alpha, nitric oxide and adhesion molecules. In other cells, in addition to IL-10 upregulation (monocytes), there is down-regulation of VACM and ECAM (endothelial cells), prostaglandins (fibroblasts) and MCP-1 and RANTES (renal tubules).CNS mediation of systemic inflammation may also be down-regulated by melanocortin receptor binding by Acthar.

Detailed description: Patients eligible for the study will be identified by the investigators and given a copy of the consent form to read. Patients interested in enrolling will be screened and if eligible will be enrolled in the study. The screening visit and the baseline visit may occur on the same day. Patients enrolling will be instructed in self-administering Acthar 80 IU twice a week. Patients will keep an injection log which will be inspected at each visit (4, 8, and 12 weeks). Ophthalmology data will be collected at each visit and recorded on the case report form by the ophthalmology technician working with the sub-investigator at the time of each visit. Patients will come to the Center for Clinical Studies each visit for blood draw, blood pressure recording, and recording of adverse events.

Eligibility criteria: Inclusion Criteria:

* Active anterior uveitis requiring oral and/or topical corticosteroid therapy

Exclusion Criteria:

* Uncontrolled diabetes
* Uncontrolled glaucoma
* HIV infection or other infection for which corticosteroid therapy contraindicated
* Contraindication to ACTHAR
* Scleroderma
* Osteoporosis
* Ocular herpes simplex
* Systemic fungal infection
* Recent surgery
* Uncontrolled hypertension

Primary outcomes:
measure: Change From Baseline in Eye With Uveitis of Anterior Chamber Cellularity Graded From 0-4 on a Likert Scale Determined by Slit Lamp Examination
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in Baseline in Eye With Uveitis of Anterior Chamber Protein Graded 0-4 on a Likert Scale Determined by Slit Lamp Evaluation
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
Study officials:
affiliation: Washington U Rheumatology
name: Richard D Brasington, MD
role: PRINCIPAL_INVESTIGATOR
References: