A study of Tocilizumab in patients with JIA associated Uveitis who have not responded to treatment with an anti-TNF.

Conditions

Juvenile Idiopathic Arthritis with Associated Uveitis MedDRA version: 18.0 Level: PT Classification code 10046851 Term: Uveitis System Organ Class: 10015919 - Eye disorders MedDRA version: 18.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue

Ramanan AV, Dick AD, Guly C, McKay A, Jones AP, Hardwick B, Lee RWJ, Smyth M, Jaki T, Beresford MW, APTITUDE Trial Management Group.

2020-02-0777 citations

10.1016/s2665-9913(20)30008-4

Interventions

Trade Name: Tocilizumab Product Name: Tocilizumab Product Code: Ro 487-7533/F10 Pharmaceutical Form: Solution for injection in pre-filled syringe

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1) Children and young people aged = 2 and =65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: 1) Uveitis without a diagnosis of JIA 2) Currently on Tocilizumab or has previously received Tocilizumab. 3) Participation in another clinical trial of investigational medicinal product within the last 4 weeks or 5 serum half-lives (whichever is longer) 4) More than 6 topical steroid eye drops per day per eye at time of screening 5) For patients on Prednisone or Prednisone equivalent, change of dose within 30 days prior to registration 6) For patients on Prednisone or Prednisone equivalent with a dose >0.2mg/kg per day 7) No intraocular injection of disease modification agents including steroids and anti-VEGF within 6 months prior to registration. 8) No intraocular surgery for previous 12 weeks or expected/panned for duration of study. 9) Lack of recovery from recent surgery or surgery 95th percentile for height / age) 26) Uncontrolled diabetes mellitus 27) History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies 28) No live attenuated vaccines (including seasonal nasal flu vaccine, varicella vaccine for shingles or chickenpox, MMR or MMRV, oral polio vaccine and vaccines for yellow fever, measles, mumps or rubella) 4 weeks prior to registration, throughout the duration of the trial and for

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of this trial is to estimate the clinical response rate of uveitis to Tocilizumab in combination with MTX in children with JIA-associated uveitis who have failed anti-TNF therapy, and to determine whether further research into the use of this intervention for the treatment of anti-TNF refractory JIA-associated uveitis should be conducted.; Secondary Objective: To conduct a preliminary evaluation of the short term safety and tolerability of Tocilizumab in combination with MTX with regards to ocular complications of treatment. Adverse events and laboratory assessments. To assess the efficacy of treatment with Tocilizumab to permit concomitant medication reduction, in particular topical and parental steroids. To determine whether further research into the use of this intervention for the treatment of anti-TNF refractory JIA associated uveitis should be conducted. ; Primary end point(s): The primary endpoint is response to treatment. Response to treatment is defined as per SUN criteria as a 2 step decrease in the level of inflammation (anterior chamber cells) or decrease to zero between baseline (prior to trial treatment initiation) and after 12 weeks of treatment ;Timepoint(s) of evaluation of this end point: 12 Weeks of treatment.	—

Measure

Time frame

Main Objective: The primary objective of this trial is to estimate the clinical response rate of uveitis to Tocilizumab in combination with MTX in children with JIA-associated uveitis who have failed anti-TNF therapy, and to determine whether further research into the use of this intervention for the treatment of anti-TNF refractory JIA-associated uveitis should be conducted.; Secondary Objective: To conduct a preliminary evaluation of the short term safety and tolerability of Tocilizumab in combination with MTX with regards to ocular complications of treatment. Adverse events and laboratory assessments. To assess the efficacy of treatment with Tocilizumab to permit concomitant medication reduction, in particular topical and parental steroids. To determine whether further research into the use of this intervention for the treatment of anti-TNF refractory JIA associated uveitis should be conducted. ; Primary end point(s): The primary endpoint is response to treatment. Response to treatment is defined as per SUN criteria as a 2 step decrease in the level of inflammation (anterior chamber cells) or decrease to zero between baseline (prior to trial treatment initiation) and after 12 weeks of treatment ;Timepoint(s) of evaluation of this end point: 12 Weeks of treatment.

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Secondary

Measure	Time frame
Secondary end point(s): 1. Safety, tolerability and compliance a) Adverse events (AEs), serious adverse events (SAEs) and Adverse Events of Special Interest (AESI) b) Laboratory parameters (haematological and biochemical analysis and urinalysis) c) Participant diaries and dosing records will determine tolerability and compliance throughout the trial treatment period 2. Use of Corticosteroids over duration of study period and throughout follow up, including: a) Total oral corticosteroid dose b) Reduction in and rate of systemic corticosteroid dose from entry dose c) Topical corticosteroid use (frequency) compared to usage at randomisation. 3. Optic and Ocular a) Visual acuity measured by Age-appropriate LogMar assessment b) Number of participants with resolution of associated optic nerve or macular oedema (as assessed by slit lamp biomicroscopy or optical coherence tomography (OCT)). c) Number of patients who are able to reduce topical or systemic agents for ocular hypertension. d) Number of participants with disease control (defined as zero cells, with topical treatment at 12 weeks treatment visit and 24 weeks treatment visit.) e) Number of participants entering disease remission (defined as zero cells, without topical treatment at 12 and 24 weeks treatment visit) f) Duration of sustaining inactive disease (zero cells, with or without topical treatment.) g) Failure to reduce eye drops to 2 drops/day by or at the 12 weeks visit 4. Quality of Life assessment (Childhood Health Questionnaire (CHQ), Childhood Health Assessment Questionnaire (CHAQ)) 5. American College of Rheumatology (ACR) Pedi core set criteria: at ACR30, ACR50, ACR70, ACR90 and ACR100 levels 6. Number particip	—

Measure

Time frame

Secondary end point(s): 1. Safety, tolerability and compliance a) Adverse events (AEs), serious adverse events (SAEs) and Adverse Events of Special Interest (AESI) b) Laboratory parameters (haematological and biochemical analysis and urinalysis) c) Participant diaries and dosing records will determine tolerability and compliance throughout the trial treatment period 2. Use of Corticosteroids over duration of study period and throughout follow up, including: a) Total oral corticosteroid dose b) Reduction in and rate of systemic corticosteroid dose from entry dose c) Topical corticosteroid use (frequency) compared to usage at randomisation. 3. Optic and Ocular a) Visual acuity measured by Age-appropriate LogMar assessment b) Number of participants with resolution of associated optic nerve or macular oedema (as assessed by slit lamp biomicroscopy or optical coherence tomography (OCT)). c) Number of patients who are able to reduce topical or systemic agents for ocular hypertension. d) Number of participants with disease control (defined as zero cells, with topical treatment at 12 weeks treatment visit and 24 weeks treatment visit.) e) Number of participants entering disease remission (defined as zero cells, without topical treatment at 12 and 24 weeks treatment visit) f) Duration of sustaining inactive disease (zero cells, with or without topical treatment.) g) Failure to reduce eye drops to 2 drops/day by or at the 12 weeks visit 4. Quality of Life assessment (Childhood Health Questionnaire (CHQ), Childhood Health Assessment Questionnaire (CHAQ)) 5. American College of Rheumatology (ACR) Pedi core set criteria: at ACR30, ACR50, ACR70, ACR90 and ACR100 levels 6. Number particip

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Countries

United Kingdom

Contacts

Public ContactBen Hardwick

Medicines for Children Clinical Trials Unit, Clinical Trials Research Centre

aptitude@liverpool.ac.uk01517064265

Outcome results

None listed