Effect of Adalimumab for the Treatment of Uveitis in Juvenile Idiopathic Arthritis

NCT01385826 | Completed Phase 2

• 1 other identifier: P081210
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to study the efficacy of adalimumab versus placebo (double-blind randomization on inclusion into 2 equal groups) on reduction of ocular inflammation quantified by laser flare photometry after two months of treatment in patients with active uveitis despite well conducted treatment with steroid eye drops and MTX. The primary objective is to demonstrate a higher response rate at 2 months in the adalimumab arm versus the placebo arm. Will be considered as responding patients those in whom the evaluated eye, 2 months after inclusion, presents at least 30% reduction of inflammation on laser flare photometry and improvement or a stable appearance on slit lamp examination. After the second month, all patients wishing to continue the trial and presenting a satisfactory clinical state will be treated with adalimumab for a total of one year after inclusion to descriptively evaluate the efficacy and safety of treatment over 10 to 12 months.

Conditions

Uveitis; Juvenile Arthritis

Keywords

Uveitis; Juvenile arthritis; Anti-tumor necrosis factor alpha monoclonal antibody; treatment

Outcome Measures

Primary Outcomes (1)

• To demonstrate that a higher proportion of subjects will have an improvement of uveitis on adalimumab versus placebo after 2 months relative to baseline

  The primary objective is to demonstrate the efficacy of 2 months of treatment with adalimumab versus placebo on reduction of ocular inflammation in JIA-associated uveitis. By defining response to treatment as a reduction of at least 30% of ocular inflammation quantified by laser flare photometry in the initially more severely inflamed eye without deterioration of cell count or flare protein on slit lamp examination, we formulate the hypothesis that at least 50% of patients treated with adalimumab for 2 months will respond to treatment versus a maximum 10% of patients on placebo.

  Final visit could occur at any point up to 78 weeks

Secondary Outcomes (6)

• Evaluation of adverse events

  12 months

• Proportion of subjects at each study time point with an improvement of uveitis

  2 months

• Eyes with active uveitis

  2 months

• The efficacy of treatment on juvenile idiopathic arthritis

  2 months

• Decrease topical or systemic steroid therapy

  12 months

Study Arms (2)

adalimumab

EXPERIMENTAL

Anti-tumor necrosis factor alpha monoclonal antibody

Drug: Anti-tumor necrosis factor alpha monoclonal antibody

placebo

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

Anti-tumor necrosis factor alpha monoclonal antibody DRUG

The dose of adalimumab will be 40 mg for children age 13 and over and for children younger than 13 adalimumab 24 mg per m2 BSA (up to a maximum total body dose of 40 mg).

adalimumab

placebo DRUG

Patients will receive 4 injections of placebo on D0, D14, D28, and D42 with assessment of the primary endpoint at M2

placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Uveitis resistant to well conducted topical steroid therapy comprising either dexamethasone or rimexolone at a dose adapted to the patient's situation as validated by one of the investigating ophthalmologists.
• Failure of systemic treatment with methotrexate at a dose of 0.3 to 0.6 mg.kg (without exceeding 25 mg) once a week for at least 3 months (except in the case of methotrexate intolerance).
• Patient who can be evaluated by laser flare photometry.
• Patient at least 4 years old on initiation of trial medication and weighing a minimum of 15 kg
• Signed informed consent both parents and/or patient's agreement
• Patient has a social security or similar

You may not qualify if:

• Systemic JIA, juvenile-onset rheumatoid arthritis, enthesitis-related JIA (with a risk of red eye uveitis).
• History of treatment with anti-TNF alpha monoclonal antibody (either adalimumab or infliximab).
• Any contraindication to administration of immunosuppressive therapy (immune deficit, opportunistic infection, other severe chronic disease)
• History of cancer or lymphoproliferative disease other than successfully and completely resected squamous cell or basal cell skin cancer,
• Any uncontrolled disease: unstable diabetes with documented history of recurrent infections, unstable ischaemic heart disease, moderate to severe heart failure (NYHA stage III/IV), recent stroke and any other disease or condition inducing, in the investigator's opinion, a risk for the patient related to his/her participation in the trial,
• Positive hepatitis B or C serology indicating active infection,
• History of positive HIV serology,
• History of clinically significant alcohol or other substance abuse during the previous year,
• Previous diagnosis or signs of demyelinating disease of the central nervous system,
• History of active tuberculosis, histoplasmosis or listeriosis,
• Signs of latent tuberculosis (based on a history of nontreated contamination, or an opacity greater than 1 cm on chest x-ray, or a positive intradermal reaction to 5 IU of tuberculin ≥ 5 mm).
• Negative urine pregnancy test in girls with childbearing potential
• Chronic rupture of the blood-aqueous barrier with marked flare on the initial examination but not modified by one month of anti-inflammatory therapy.
• Impossibility to monitor flare:
• Children \< 4 years

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Abbott: collaborator
• URC-CIC Paris Descartes Necker Cochin: collaborator

Study Sites (1)

Hospital of necker Enfants malades

Paris, 75015, France

Location

Related Publications (6)

• Quartier P, Baptiste A, Despert V, Allain-Launay E, Kone-Paut I, Belot A, Kodjikian L, Monnet D, Weber M, Elie C, Bodaghi B; ADJUVITE Study Group. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Ann Rheum Dis. 2018 Jul;77(7):1003-1011. doi: 10.1136/annrheumdis-2017-212089. Epub 2017 Dec 23.

  PMID: 29275333 BACKGROUND

• Simonini G, Taddio A, Cattalini M, Caputo R, De Libero C, Naviglio S, Bresci C, Lorusso M, Lepore L, Cimaz R. Prevention of flare recurrences in childhood-refractory chronic uveitis: an open-label comparative study of adalimumab versus infliximab. Arthritis Care Res (Hoboken). 2011 Apr;63(4):612-8. doi: 10.1002/acr.20404.

  PMID: 21452272 BACKGROUND

• Callejas-Rubio JL, Sanchez-Cano D, Serrano JL, Ortego-Centeno N. Adalimumab therapy for refractory uveitis: a pilot study. J Ocul Pharmacol Ther. 2008 Dec;24(6):613-4; author reply 614. doi: 10.1089/jop.2008.0073. No abstract available.

  PMID: 19049264 BACKGROUND

• Tynjala P, Kotaniemi K, Lindahl P, Latva K, Aalto K, Honkanen V, Lahdenne P. Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis. Rheumatology (Oxford). 2008 Mar;47(3):339-44. doi: 10.1093/rheumatology/kem356. Epub 2008 Jan 31.

  PMID: 18238789 BACKGROUND

• Biester S, Deuter C, Michels H, Haefner R, Kuemmerle-Deschner J, Doycheva D, Zierhut M. Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007 Mar;91(3):319-24. doi: 10.1136/bjo.2006.103721. Epub 2006 Oct 11.

  PMID: 17035274 BACKGROUND

• Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr. 2006 Oct;149(4):572-5. doi: 10.1016/j.jpeds.2006.04.058.

  PMID: 17011337 BACKGROUND

MeSH Terms

Conditions

Uveitis; Arthritis, Juvenile

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Pierre Quartier dit Maire, MD, PhD

  hospital Necker Enfants Malades

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2011
• First Posted: June 30, 2011
• Study Start: June 29, 2011
• Primary Completion: November 4, 2014
• Study Completion: August 27, 2015
• Last Updated: September 8, 2025

Record last verified: 2025-09

Locations

FR (1)