Tocilizumab in the Management of Juvenile Idiopathic Arthritis Associated Uveitis

This study is currently recruiting participants.
Verified November 2013 by Oregon Health and Science University
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Eric B. Suhler, Oregon Health & Science University
ClinicalTrials.gov Identifier:
NCT01603355
First received: May 18, 2012
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

The investigators are doing this research study to see if tocilizumab (Actemra) is safe and effective when used for severe or refractory non-infectious uveitis. Uveitis is an inflammation of the eye that is caused by the body's immune system reacting against the eye tissues.


Condition Intervention Phase
Juvenile Idiopathic Arthritis Associated Uveitis
Drug: Tocilizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Trial to Assess the Efficacy and Safety of Tocilizumab in the Management of Juvenile Idiopathic Arthritis Associated Vision-threatening Uveitis That is Refractory to Other Modes of Systemic Immunosuppression

Resource links provided by NLM:


Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:
  • Anterior Chamber Cell [ Time Frame: 16 Weeks ] [ Designated as safety issue: No ]
    control of anterior chamber cell in both eyes at week 16 to a level of trace or less (SUN criteria) without an increase in any immunosuppressive treatment and while using prednisolone acetate topically no more than 2 times per day


Estimated Enrollment: 5
Study Start Date: November 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab Drug: Tocilizumab

Intravenous tocilizumab:

Patients less than 30 kg weight:10 mg per kg every 4 weeks Patients at or above 30 kg weight: 8 mg per kg every 4 weeks

Other Name: Actemra

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with Juvenile Idiopathic Arthritis
  • Subjects with vision-threatening autoimmune uveitis.
  • Failure to respond to methotrexate or at least one other systemic immunosuppressive or intolerance to such medications due to side effects. Failure to respond includes presence of one plus or greater anterior chamber cell in both eyes; need for topical corticosteroid four times or more in either eye; ocular hypertension or glaucoma attributable to the topical corticosteroid.
  • Subjects with bilateral disease.
  • If subjects are on oral corticosteroids, the dosage must be stable for 2 weeks prior to baseline and not exceed 10 mg per day or 2mg/kg/day (whichever is less) of prednisone or its equivalent. Subjects must be willing to agree to not alter the dosage of oral steroids during the first 16 weeks of the trial.
  • Must have a chest radiograph within 3 months prior to enrollment with no evidence of malignancy, infection or fibrosis.
  • Parent or guardian must understand and voluntarily sign an informed consent form.
  • Pediatric subjects of either gender 2-17 years at time of consent.

Exclusion Criteria:

  • Inability of parent or guardian to provide voluntary consent
  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned surgery within 12 months following randomization.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Pregnant or breastfeeding
  • Current liver disease, as determined by the Principal Investigator on the basis of history or serum studies
  • History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies including tocilizumab.
  • Evidence of significant uncontrolled concomitant diseases such as nervous system, renal, hepatic (patients with prior history of ALT elevation will not be excluded), endocrine, or gastrointestinal (GI) disorders, which in the Investigator's opinion, would preclude patient participation.
  • Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids.
  • Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
  • History of active mycobacterial infection with any species (including Mycobacterium tuberculosis) within 2 years prior to screening visit. Subjects with Mycobacterium tuberculosis infection more than 2 years prior to screening visit are allowed if successful treatment was completed at least 2 years prior to randomization and is documented and available for verification.
  • Immunization with a live/attenuated vaccine within 4 weeks prior to baseline
  • Latent Mycobacterium tuberculosis infection as indicated by a positive Purified Protein Derivative [PPD] skin test. Subjects with a positive PPD skin test and documented completion of treatment for latent TB are eligible. Subjects with a positive PPD skin test and not treated or no documentation of completion of treatment are ineligible.
  • If QuantiFERON® test is performed instead of the PPD test, only those with a negative QuantiFERON® test are allowed in the study.
  • History of incompletely treated Mycobacterium tuberculosis infection as indicated by

    • Subject's medical records documenting incomplete treatment for Mycobacterium tuberculosis
    • Subject's self-reported history of incomplete treatment for Mycobacterium tuberculosis
  • History of recurrent bacterial infection (at least 3 major infections resulting in hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years) or recurrent viral, fungal, mycobacterial, or other infections (including but not limited to atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds)
  • Clinically significant abnormality on the chest x-ray (CXR) at screening. Chest x-rays performed within 3 months prior to start of study drug are acceptable.
  • Use of any investigational medication within 4 weeks prior to start of study drug or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer)
  • History of congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency [CVID])
  • Hepatitis B surface antigen positive or Hepatitis B core antibody positive at screening
  • History of Human Immunodeficiency Virus (HIV) infection
  • Antibodies to Hepatitis C at screening
  • Malignancy or history of malignancy (except for treated [ie, cured] basal-cell skin carcinomas > 3 years prior to screening)
  • Have multiple sclerosis or other central demyelinating disorder.
  • Presence of a transplanted organ (with the exception of a corneal transplant performed > 3 months prior to enrollment).
  • History of substance abuse (drug or alcohol) within the previous 3 years, history of noncompliance to medical regimens, or other condition/circumstance that could interfere with the subject's adherence to protocol requirements.
  • Previous or current use of an alkylating agent (e.g. chlorambucil or cyclophosphamide).
  • Treatment with etoposide (VP16) within 3 months prior to the baseline visit.
  • Administration of intravenous immunoglobulin for the treatment of active polyarticular disease within 4 weeks prior to the baseline visit.
  • Previous treatment with any cell depleting therapies, including investigational agents (e.g. anti-CD19 and anti-CD20).
  • Prior stem cell transplant at any time.
  • TNF -blocker use within the 8-weeks prior to enrollment (Infliximab use within 10 weeks prior to enrollment).
  • Laboratory Exclusion criteria (at screening):

    • Serum creatinine >1.5 ULN (upper limit of normal for age and sex);
    • AST or ALT > 1.5 ULN (upper limit of normal for age and sex);
    • Total bilirubin > 1.3 mg/dL (> 23 umol/L);
    • Platelet count < 150 x 103/μL (< 150,000/mm3);
    • Hemoglobin < 9.0 g/dL (< 3.7 mmol/L);
    • WBC count < 5,000/mm3 (< 5.0 x 109/L);
    • Neutrophil count < 2,500/ mm3 (< 2.5 x 109/L)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01603355

Contacts
Contact: Eric B Suhler, MD 503-494-5023 suhlere@ohsu.edu
Contact: Tracy R Giles, BS 503-494-0482 gilest@ohsu.edu

Locations
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Tracy R Giles, BS    503-494-0482    gilest@ohsu.edu   
Sponsors and Collaborators
Eric B. Suhler
Genentech
Investigators
Principal Investigator: Eric B Suhler, MD,MPH Oregon Health and Science University
Study Director: James T Rosenbaum, MD Oregon Health and Science University
  More Information

No publications provided

Responsible Party: Eric B. Suhler, Principal Investigator, Oregon Health & Science University
ClinicalTrials.gov Identifier: NCT01603355     History of Changes
Other Study ID Numbers: e8343
Study First Received: May 18, 2012
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:
JIA

Additional relevant MeSH terms:
Arthritis
Uveitis
Chorioretinitis
Arthritis, Juvenile Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Uveal Diseases
Eye Diseases
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis
Arthritis, Rheumatoid
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 20, 2014