A study to assess the pharmacokinetics and safety of tocilizumab in patients with Active Systemic Juvenile Idiopathic Arthritis.

• Register: EUCTR
• Last refreshed on: 24 October 2016
• Main ID: EUCTR2015-000435-33-ES
• Date of registration: 29/06/2015
• Prospective Registration: No
• Primary sponsor: Roche Farma S.A en nombre de F. Hoffmann-La Roche Ltd
• Public title: A study to assess the pharmacokinetics and safety of tocilizumab in patients with Active Systemic Juvenile Idiopathic Arthritis.
• Scientific title: A phase I pharmacokinetic and safety study of tocilizumab (TCZ) in patients less than 2 years old with active systemic juvenile idiopathic arthritis (sJIA)
• Date of first enrolment: 26/06/2015
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000435-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Germany, Hungary, Italy, Poland, Russian Federation, Spain, United Kingdom

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F.Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
- Age less than 24 months at baseline
- Fulfills International League of Associations for Rheumatology classification criteria for sJIA
- Duration of sJIA lasting at least 1 month since onset of sJIA symptoms
- Presence of active disease as determined by the presence of >=2 active joints at screening and baseline, with at least 14 consecutive days of temperature recordings to identify presence or absence of fever (>=38°C) during screening and baseline; or >=2 active joints at screening and baseline, with a fever >=38°C for at least 5 consecutive days during screening and baseline; under these circumstances a patient does not need to complete a full 14 days of temperature diary entries to meet this inclusion criteria
- Not currently receiving corticosteroids (CS) OR if taking oral CS, receiving prednisone or equivalent at a stable dose of <=1 milligrams per kilograms per day (mg/kg/day); and the dose remained stable for at least 2 weeks prior to baseline
- Not currently receiving methotrexate (MTX) OR if taking MTX, the dose has remained stable or has been discontinued for at least 4 weeks prior to baseline
- Not currently receiving non-steroidal anti-inflammatory drug (NSAID) OR if taking NSAID, the dose has remained stable or has been discontinued for at least 2 weeks prior to baseline
- Never treated with biologics except anakinra which has been discontinued >=1 week prior to the baseline visit
Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Any other auto-immune, rheumatic disease or overlap syndrome other than sJIA
- Any significant concurrent medical or surgical condition which would jeopardize the patient?s safety or ability to complete the trial or planned surgery during the study (myringotomy surgery does not exclude patient)
- Evidence of serious uncontrolled concomitant diseases including but not limited to the nervous system, renal, hepatic, or endocrine systems
- Asthma for which the patient has required the use of oral or parenteral corticosteroids for >=2 weeks within 6 months prior to the baseline visit
- Any active acute, subacute, chronic or recurrent bacterial, viral, or systemic fungal infection including but not limited to: acute or chronic renal / bladder infections; acute or chronic pulmonary infections
- History of atypical tuberculosis (TB) and active TB requiring treatment at any point prior to screening visit and positive TB test result at screen, unless treated with anti-tuberculosis therapy for at least 4 weeks prior to receiving study medication and chest radiograph is negative for active tuberculosis
- Any major episode of infection requiring hospitalization or treatment during screening or treatment with intravenous antibiotics completing within 4 weeks of the screening visit or oral antibiotics completing within 2 weeks of the screening visit
- History of reactivation or new onset of a systemic infection such as herpes zoster or Epstein Barr virus within 2 months of the screening visit
- Significant cardiac or pulmonary disease
- History or concurrent serious gastrointestinal disorders such as ulcer or inflammatory bowel disease, ulcerative colitis or other symptomatic lower gastrointestinal conditions, including ulcer and perforation;
- History of or current cancer or lymphoma
- History of macrophage activation syndrome within 1 month prior to the screening visit
- Administration of intravenous immunoglobulin 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
- Live or attenuated vaccines within 4 weeks prior to the baseline visit, or intending to receive while on study medication or 8 weeks following the last dose of study medication


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic Juvenile Idiopathic Arthritis (sJIA)
MedDRA version: 18.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Roactemra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Other descriptive name: IL-6 receptor inhibitor, recombinant humanized monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: To evaluate safety of TCZ over 12 weeks in combination with stable ongoing therapy.
To evaluate PD and appropriate efficacy of TCZ over 12 weeks in combination with stable ongoing therapy.

Main Objective: To evaluate the pharmacokinetics of Tocilizumab (TCZ) over 12 weeks in patients less than 2 years of age with sJIA.

Timepoint(s) of evaluation of this end point: Week 12

Primary end point(s): Pharmacokinetic: Serum TCZ concentration assessed by area under the serum concentration-time profile (AUC[2weeks]), maximum concentration observed (Cmax), and minimum concentration under steady-state conditions within a dosing interval (Cmin)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Up to 18 weeks
2-3. Up to 21 weeks

Secondary end point(s): 1. Safety: Adverse events
2. Safety: Clinical laboratory results
3. Safety: Physical examination including vital signs

Secondary ID(s)

NCT01455701

2015-000435-33-DE

NP25737

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd