Tocilizumab in the Management of Juvenile Idiopathic Arthritis Associated Uveitis

NCT ID: NCT01603355

Last Updated: 2019-01-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2016-02-29

Brief Summary

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.

Conditions

Juvenile Idiopathic Arthritis Associated Uveitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Actemra

Eligibility 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).

• 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)

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Eric B. Suhler

OTHER

Sponsor Role: lead

Responsible Party

Eric B. Suhler

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Eric B Suhler, MD,MPH

Role: PRINCIPAL_INVESTIGATOR

Oregon Health and Science University

James T Rosenbaum, MD

Role: STUDY_DIRECTOR

Oregon Health and Science University

Locations

Oregon Health & Science University

Portland, Oregon, United States

Countries

United States

Other Identifiers

e8343

Identifier Type: -

Identifier Source: org_study_id