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Multi Center Prospective Registry of Infliximab Use for Childhood Uveitis

Primary Purpose

Chronic Uveitis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
infliximab
infliximab
Sponsored by
Egla C. Rabinovich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Uveitis focused on measuring Childhood, Uveitis

Eligibility Criteria

4 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:. Ages 4 to 18 years old, Non-infectious uveitis Persistent uveitis uncontrolled by topical medications, or unacceptable side effects of topical medications. Failure of at least six weeks of treatment with a non-biological disease modifying agent such as methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine. Ability to provide informed consent (subject or parent/guardian) Onset of uveitis < 16 years of age. Topical ophthalmologic treatments allowed. Systemic corticosteroid use at entry may be allowed. Willingness to use acceptable contraception if sexually active for the duration of the study and for 6 months after receiving the last infliximab infusion. Concomitant methotrexate must be taken at time of initiation of infliximab Participant must be able to cooperate for a non-sedated slit lamp exam and visual acuity examination. Negative Purified Protein Derivative (PPD) placed and read within 1 month of initiation of infliximab 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: Previous use of biologic medications for uveitis. Intraocular steroid injection or ophthalmologic surgery within the preceding 3 months. Uveitis due to trauma or intraocular surgery Females who are pregnant, nursing, or planning pregnancy within 6 months after the last infliximab infusion. Males who plan on fathering a child within 6 months after their last infliximab infusion. A history of a known allergy to murine products. Documentation of seropositivity for human immunodeficiency virus (HIV). Documentation of a positive test for hepatitis B surface antigen or hepatitis C A known history of a serious infection (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months. An opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening. A concomitant diagnosis or history of congestive heart failure. A history of lymphoproliferative disease. Any known malignancy or a history of malignancy. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease. 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. Presence of a transplanted solid organ.

Sites / Locations

  • Duke University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

5mg/kg/dose of infliximab IV every 4 weeks for 9 doses

10mg/kg/dose of infliximab IV every 4 weeks for 9 doses.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
December 27, 2007
Last Updated
August 22, 2013
Sponsor
Egla C. Rabinovich
Collaborators
Childhood Arthritis and Rheumatology Research Alliance
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1. Study Identification

Unique Protocol Identification Number
NCT00589628
Brief Title
Multi Center Prospective Registry of Infliximab Use for Childhood Uveitis
Official Title
Multi Center Prospective Registry of Infliximab Use for Childhood Uveitis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2013
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
December 2010 (Actual)
Study Completion Date
December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Egla C. Rabinovich
Collaborators
Childhood Arthritis and Rheumatology Research Alliance

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Uveitis
Keywords
Childhood, Uveitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
5mg/kg/dose of infliximab IV every 4 weeks for 9 doses
Arm Title
2
Arm Type
Active Comparator
Arm Description
10mg/kg/dose of infliximab IV every 4 weeks for 9 doses.
Intervention Type
Drug
Intervention Name(s)
infliximab
Other Intervention Name(s)
Remicade
Intervention Description
5mg/kg/dose IV at 4 week intervals
Intervention Type
Drug
Intervention Name(s)
infliximab
Other Intervention Name(s)
Remicade
Intervention Description
10mg/kg/dose IV at 4 week intervals
Primary Outcome Measure Information:
Title
Effects of Infliximab on Uveitis Disease Activity.
Description
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.
Time Frame
9 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:. Ages 4 to 18 years old, Non-infectious uveitis Persistent uveitis uncontrolled by topical medications, or unacceptable side effects of topical medications. Failure of at least six weeks of treatment with a non-biological disease modifying agent such as methotrexate, cyclosporine, mycophenolate mofetil, or azathioprine. Ability to provide informed consent (subject or parent/guardian) Onset of uveitis < 16 years of age. Topical ophthalmologic treatments allowed. Systemic corticosteroid use at entry may be allowed. Willingness to use acceptable contraception if sexually active for the duration of the study and for 6 months after receiving the last infliximab infusion. Concomitant methotrexate must be taken at time of initiation of infliximab Participant must be able to cooperate for a non-sedated slit lamp exam and visual acuity examination. Negative Purified Protein Derivative (PPD) placed and read within 1 month of initiation of infliximab 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: Previous use of biologic medications for uveitis. Intraocular steroid injection or ophthalmologic surgery within the preceding 3 months. Uveitis due to trauma or intraocular surgery Females who are pregnant, nursing, or planning pregnancy within 6 months after the last infliximab infusion. Males who plan on fathering a child within 6 months after their last infliximab infusion. A history of a known allergy to murine products. Documentation of seropositivity for human immunodeficiency virus (HIV). Documentation of a positive test for hepatitis B surface antigen or hepatitis C A known history of a serious infection (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months. An opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening. A concomitant diagnosis or history of congestive heart failure. A history of lymphoproliferative disease. Any known malignancy or a history of malignancy. Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease. 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. Presence of a transplanted solid organ.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Egla Rabinovich, MD. MPH
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22438273
Citation
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.
Results Reference
background
PubMed Identifier
17953940
Citation
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.
Results Reference
background
PubMed Identifier
16461435
Citation
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.
Results Reference
result
PubMed Identifier
16545455
Citation
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.
Results Reference
result
PubMed Identifier
16406545
Citation
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.
Results Reference
result
Links:
URL
http://carragroup.org
Description
Research Information. Click on current studies

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Multi Center Prospective Registry of Infliximab Use for Childhood Uveitis

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