Multi Center Prospective Registry of Infliximab Use for Childhood Uveitis

Phase 4

Completed

• Conditions: Chronic Uveitis
• Interventions: Drug: infliximab

• Registration Number: NCT00589628
• Lead Sponsor: Egla C. Rabinovich

Brief Summary

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.

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 Timeline

• Study Start: 2007-09
• Study First Submitted: 2007-12-27
• Study First Submitted QC: 2008-01-09
• Study First Posted: 2008-01-10
• Primary Completion: 2010-12
• Study Completion: 2010-12
• Results First Submitted: 2013-02-21
• Status Verified: 2013-08
• Results First Submitted QC: 2013-08-22
• Last Update Submitted: 2013-08-22
• Results First Posted: 2013-08-26
• Last Update Posted: 2013-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	infliximab	5mg/kg/dose of infliximab IV every 4 weeks for 9 doses
2	infliximab	10mg/kg/dose of infliximab IV every 4 weeks for 9 doses.

Primary Outcome Measures

Name	Time	Method
Effects of Infliximab on Uveitis Disease Activity.	9 months	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.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States