Multi Center Prospective Registry of Infliximab Use for Childhood Uveitis

The primary objective of this study is to examine the efficacy of infliximab for the treatment of persistent uveitis in children. Participants (4-18 years of age) will be randomly assigned to either 5mg/kg or 10mg/kg dose of infliximab to be administered by intravenous infusion at four week intervals. Participant responses will be measured at at four to eight week intervals for up to ten months.

Study Overview

• Status: Completed
• Conditions: Chronic Uveitis
• Intervention / Treatment: Drug: infliximab; Drug: infliximab

Detailed Description

Pediatric rheumatologists often use infliximab in the treatment of childhood uveitis, at this time there are no prospective studies for this use. Participants will be randomized to initial suggested dose of infliximab (5 mg/kg/dose vs 10 mg/kg/dose) and data will be collected prospectively with regard to ophthalmologic outcomes. Study participants will be followed for up to 10 months to determine efficacy and side effects, and an additional 30 days for safety reports. Descriptive statistics will be gathered on participant demographics, uveitis characteristics, change in immunosuppressive medications, number of responders, ophthalmologic measures and change in corticosteroid dose during the study period. Initial to final dose will be examined by paired t-test. The proportion of responders in the 5 mg/kg initial dose group will be compared to the 10 mg/kg/dose by a Chi-square or Fisher's exact test, depending on numbers available. Predictors of response will be examined by logistic regression.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:.

1. Ages 4 to 18 years old,
2. Non-infectious uveitis
3. Persistent uveitis uncontrolled by topical medications, or unacceptable side effects of topical medications.
4. Failure of at least six weeks of treatment with a non-biological disease modifying agent such as methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine.
5. Ability to provide informed consent (subject or parent/guardian)
6. Onset of uveitis < 16 years of age.
7. Topical ophthalmologic treatments allowed.
8. Systemic corticosteroid use at entry may be allowed.
9. Willingness to use acceptable contraception if sexually active for the duration of the study and for 6 months after receiving the last infliximab infusion.
10. Concomitant methotrexate must be taken at time of initiation of infliximab
11. Participant must be able to cooperate for a non-sedated slit lamp exam and visual acuity examination.
12. Negative Purified Protein Derivative (PPD) placed and read within 1 month of initiation of infliximab

13. The screening laboratory test results must meet the following criteria:

    • WBC (white blood cell count): within normal range for institution
    • ANC (absolute neutrophil count): within normal range for institution
    • Hemoglobin: greater than 10 grams/deciliter
    • Platelets: within normal range for institution
    • Serum Creatinine: within normal range for age
    • AST - aspartate aminotransferase - within normal range for institution
    • ALT - alanine aminotransferase- within normal range for institution

Exclusion Criteria:

1. Previous use of biologic medications for uveitis.
2. Intraocular steroid injection or ophthalmologic surgery within the preceding 3 months.
3. Uveitis due to trauma or intraocular surgery
4. Females who are pregnant, nursing, or planning pregnancy within 6 months after the last infliximab infusion.
5. Males who plan on fathering a child within 6 months after their last infliximab infusion.
6. A history of a known allergy to murine products.
7. Documentation of seropositivity for human immunodeficiency virus (HIV).
8. Documentation of a positive test for hepatitis B surface antigen or hepatitis C
9. A known history of a serious infection (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
10. An opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
11. A concomitant diagnosis or history of congestive heart failure.
12. A history of lymphoproliferative disease.
13. Any known malignancy or a history of malignancy.
14. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
15. Use of any investigational drug within 30 days prior to screening or within five half-lives of the first dose of the investigational agent, whichever is longer.
16. Presence of a transplanted solid organ.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; 5mg/kg/dose of infliximab IV every 4 weeks for 9 doses	Drug: infliximab; 5mg/kg/dose IV at 4 week intervals; Other Names: Remicade; Drug: infliximab; 10mg/kg/dose IV at 4 week intervals; Other Names: Remicade
ACTIVE_COMPARATOR: 2; 10mg/kg/dose of infliximab IV every 4 weeks for 9 doses.	Drug: infliximab; 5mg/kg/dose IV at 4 week intervals; Other Names: Remicade; Drug: infliximab; 10mg/kg/dose IV at 4 week intervals; Other Names: Remicade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Infliximab on Uveitis Disease Activity.	Number of subjects with improvement in uveitis, defined as a two step decrease in level of inflammation (as defined by SUN criteria, AC cells, vitreous haze) or decrease to grade 0. A grading scheme of 0 indicating (<1 cell/ocular field) low levels of inflammation to 4+ indicating (>50 cells/ocular field) indicating high levels of inflammation.	9 months

Collaborators and Investigators

• Sponsor: Egla C. Rabinovich
• Collaborators: Childhood Arthritis and Rheumatology Research Alliance
• Investigators: Principal Investigator: Egla Rabinovich, MD. MPH, Duke University

Publications and helpful links

General Publications

• Heiligenhaus A, Foeldvari I, Edelsten C, Smith JR, Saurenmann RK, Bodaghi B, de Boer J, Graham E, Anton J, Kotaniemi K, Mackensen F, Minden K, Nielsen S, Rabinovich EC, Ramanan AV, Strand V; Multinational Interdisciplinary Working Group for Uveitis in Childhood. Proposed outcome measures for prospective clinical trials in juvenile idiopathic arthritis-associated uveitis: a consensus effort from the multinational interdisciplinary working group for uveitis in childhood. Arthritis Care Res (Hoboken). 2012 Sep;64(9):1365-72. doi: 10.1002/acr.21674.
• Ardoin SP, Kredich D, Rabinovich E, Schanberg LE, Jaffe GJ. Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up. Am J Ophthalmol. 2007 Dec;144(6):844-849. doi: 10.1016/j.ajo.2007.08.018. Epub 2007 Oct 22.
• Saurenmann RK, Levin AV, Rose JB, Parker S, Rabinovitch T, Tyrrell PN, Feldman BM, Laxer RM, Schneider R, Silverman ED. Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology (Oxford). 2006 Aug;45(8):982-9. doi: 10.1093/rheumatology/kel030. Epub 2006 Feb 3.
• Kahn P, Weiss M, Imundo LF, Levy DM. Favorable response to high-dose infliximab for refractory childhood uveitis. Ophthalmology. 2006 May;113(5):860-4.e2. doi: 10.1016/j.ophtha.2006.01.005. Epub 2006 Mar 20.
• Rajaraman RT, Kimura Y, Li S, Haines K, Chu DS. Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006 Feb;113(2):308-14. doi: 10.1016/j.ophtha.2005.09.037. Epub 2006 Jan 10.

Helpful Links

• Research Information. Click on current studies

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): December 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: December 27, 2007
• First Submitted That Met QC Criteria: January 9, 2008
• First Posted (ESTIMATE): January 10, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 22, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Uveitis; Childhood
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Infliximab
• Other Study ID Numbers: Pro00000057