A study of a new sub-cutaneous formulation of Actemra/RoActemra in children with systemic juvenile idiopathic arthritis

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2012-003490-26-DE
• Date of registration: 05/06/2013
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A study of a new sub-cutaneous formulation of Actemra/RoActemra in children with systemic juvenile idiopathic arthritis
• Scientific title: A PHASE Ib, OPEN-LABEL, MULTICENTER STUDY TO INVESTIGATE THE PHARMACOKINETICS, PHARMACODYNAMICS, AND SAFETY OF TOCILIZUMAB FOLLOWING SUBCUTANEOUS ADMINISTRATION TO PATIENTS WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS
• Date of first enrolment: 08/08/2013
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003490-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Canada, France, Germany, Italy, Mexico, Russian Federation, Spain, United Kingdom, United States

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:
- Ages 1 (12 for patients in Russia) year up to and including 17 years at screening
- Diagnosis of systemic juvenile idiopathic arthritis
- Inadequate clinical response (in the opinion of the treating physician) to non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids
- Concurrent treatment with disease-modifying anti-rheumatic drugs (DMARDs) (including methotrexate [MTX]), NSAIDs, and oral corticosteroids is permitted at the discretion of the investigator.
- Discontinuation of biologic agents (other than tocilizumab if the patient is receiving IV TCZ) for 4 days -20 weeks prior to baseline depending on biologic agent
- Female patients of childbearing potential and male patients with a female partner of childbearing potential must agree with the required contraceptive methods as defined per protocol.
Are the trial subjects under 18? yes
Number of subjects for this age range: 48
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:
- Prior discontinuation of IV TCZ because of inadequate clinical response or safety events
- Patients with poorly controlled disease (in the opinion of the treating physician) despite current treatment with IV TCZ
- sJIA that is well controlled by any treatment agent other than TCZ (Juvenile Arthritis Disease Activity Score (JADAS) -71=3.8 with no fever)
- Patients who are wheelchair-bound or bedridden
- Any other auto-immune, rheumatic disease, or overlapping syndrome other than sJIA
- Prior stem cell transplant at any time


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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Trade Name: RoActemra
Product Name: tocilizumab SC
Product Code: Ro 487-7533/F10-04
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Other descriptive name: recombinant antihumanized anti-human monoclonal antibody directed against the IL-6R
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 180-

Primary Outcome(s)

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: - Pharmacokinetic endpoints will be evaluated at fixed timepoints during the first 14 weeks of the study [Weeks 0-14]
- Pharmacodynamic endpoints will be evaluated at fixed timepoints during the first 14 weeks of the study [Weeks 0-14]
- Adverse events, adverse events of special interest and clinical laboratory abnormalities will be recorded for the entire duration of the study [Weeks 0-52]
- The presence of anti-TCZ antibodies will be evaluated at baseline and at regular intervals with event-driven testing in cases of anaphylaxis, serious hypersensitivity events, or any hypersensitivity event (including non-serious events) leading to treatment withdrawal (at the time of the event and at least 8 weeks after the event)

Main Objective: Primary Objective
- To characterize the pharmacokinetics of subcutaneous tocilizumab (SC TCZ) in patients with sJIA
- To evaluate the pharmacodynamics of SC TCZ in patients with sJIA
- To evaluate the safety of SC TCZ in patients with sJIA

Primary end point(s): - Serum TCZ concentration and population PK model-predicted PK exposures area under the concentration-time curve (AUC) , maximum plasma concentration (Cmax ) and Cmin) for the initial QW and Q10D dosing regimens at steady state, and the Q2W dosing regimen at steady state in the <30 kg patients
- Serum IL-6 and soluble IL-6R (sIL-6R) levels, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)
- The incidence and severity of adverse events (including local injection-site reactions) and serious adverse events
- The incidence and severity of adverse events of special interest
- The incidence and severity of clinical laboratory abnormalities
- The incidence of anti-TCZ antibodies

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

WA28118

NCT01904292

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd