A Study to Evaluate Pharmacokinetics and Safety of Tocilizumab (RoActemra/Actemra) in Participants Less Than 2 Years Old With Active Systemic Juvenile Idiopathic Arthritis (sJIA)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01455701
• Date of registration: 18/10/2011
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study to Evaluate Pharmacokinetics and Safety of Tocilizumab (RoActemra/Actemra) in Participants Less Than 2 Years Old With Active Systemic Juvenile Idiopathic Arthritis (sJIA)
• 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: October 26, 2012
• Target sample size: 11
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01455701
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Argentina, Belgium, Canada, France, Germany, Hungary, Poland, Russian Federation, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Fulfils international league of associations for rheumatology (ILAR) classification
criteria for sJIA

- Duration of sJIA symptoms lasting for at least 1 months subsequent to diagnosis of
sJIA

- Presence of active disease as determined by the presence of:

1. Greater than or equal to (>=) 2 active joints at screening and baseline, with at
least 14 consecutive days of temperature recordings, which may include the
presence or absence of fever (>=38 degree Celsius) during the time between
screening and baseline; or

2. >=2 active joints at screening and baseline, with a fever >=38 degree Celsius for
at least 5 consecutive days during the time between screening and baseline; under
these circumstances a participant 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 like prednisone or
equivalent, the dose should be less than or equal to (<=) 1 milligram per kilogram per
day (mg/kg/day) and the dose has remained stable for at least 2 weeks prior to
baseline

- Not currently receiving methotrexate (MTX) or if taking MTX (together with either
folic acid or folinic acid according to local standard-of-care), the dose has remained
stable or has been discontinued for at least 4 weeks prior to baseline

- Not currently receiving non-steroidal anti-inflammatory drugs (NSAIDs) or if taking
NSAID, the dose has remained stable or has been discontinued for at least 2 weeks
prior to baseline

- If the participants has received previous treatment with any of the following biologic
agents, these must have been discontinued according to the following timelines prior
to the baseline visit and are not permitted during the study:

1. Etanercept must have been discontinued within >= 2 weeks prior to baseline

2. Anakinra must have been discontinued within >= 4 days prior to baseline

3. Abatacept must have been discontinued within >= 12 weeks prior to baseline

4. Infliximab or adalimumab must have been discontinued within >= 8 weeks prior to
baseline

5. Canakinumab must have been discontinued within >= 20 weeks prior to baseline

6. Rilonacept must have been discontinued within >= 6 weeks prior to baseline

7. Golimumab must have been discontinued within >= 10 weeks prior to baseline

8. Certrolizumab pegol must have been discontinued within >= 10 weeks prior to
baseline

- History of inadequate clinical response (in the opinion of the treating physician) to
NSAIDs and CS

Exclusion Criteria:

General Exclusion Criteria:

- Any autoimmune, rheumatic disease or overlap syndrome other than sJIA

- Not fully recovered from recent surgery or less than 6 weeks since surgery, at the
time of screening visit; or planned surgery during the study (except for myringotomy
surgery, which is permitted)

General Safety Exclusion Criteria:

- Any significant concurrent medical or surgical condition which would jeopardize the
participant's safety or ability to complete the trial

- History of significant allergic or infusion reactions to prior biologic therapy or to
any of the excipients listed in tocilizumab product labelling documents

- Inborn conditions characterized by a compromised immune system

- Known human immunodeficiency virus (HIV) infection or other acquired forms of immune
compromise

- Evidence of serious uncontrolled concomitant diseases including but not limited to the
nervous system, renal, hepatic or endocrine systems

- Asthma for which the participant has required the use of oral or parenteral
corticosteroids for >=2 weeks within 6 months prior to baseline visit

- Any active acute, subacute, chronic or recurrent bacterial, viral or systemic fungal
infection

- History of atypical tuberculosis (TB)

- Active TB requiring treatment at any point prior to screening visit

- Positive TB test result at screen, unless treated with anti-TB therapy for at least 4
weeks prior to receiving study medication and chest radiograph is negative for active
TB within 6 months of screening visit consistent with local practice

- Any major episode of infection requiring hospitalization or treatment during screening
or treatment with IV 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

- History of hepatitis B or hepatitis C infection

- Chronic hepatitis - viral or autoimmune

- 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 (MAS) within 3 months prior to the screening
visit

- Uncontrolled diabetes mellitus with elevated hemoglobin A1c (HbA1c) as defined by
age-specific standards

Excluded Previous or Concomitant Therapy:

- Participation in another interventional clinical trial within the past 30 days or 5
serum half-lives of the investigative medication, whichever is longer

- Previous treatment with tocilizumab

- Administration of IV immunoglobulin within 4 weeks prior to the baseline visit

- Previous treatment with any cell depleting therapies, including investigational agents

- 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

- 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 < 200 x103/µL (< 200,000/mm3)

- Hemoglobin < 7.0 g/dL (< 4.3 mmol/L)

- WBC count < 6,200/mm3 (< 6.2 x 109/L)

- Neutrophil count < 2,500/ mm3 (< 2.5x 109/L)



Age minimum: N/A
Age maximum: 24 Months
Gender: All

Health Condition(s) or Problem(s) studied

Juvenile Idiopathic Arthritis

Intervention(s)

Drug: Tocilizumab

Primary Outcome(s)

Maximum Serum Concentration (Cmax) of Tocilizumab [Time Frame: Pre-infusion (Hour 0) on Days 1, 15, 29, 43, 57, 71, and 85; at the end of infusion on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 (infusion length = 1 hour)]

Minimum Serum Concentration (Cmin) of Tocilizumab [Time Frame: Pre-infusion (Hour 0) on Days 1, 15, 29, 43, 57, 71, and 85; at the end of infusion on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 (infusion length = 1 hour)]

Model predicted Area Under the Serum Concentration-Time Curve from Time Zero to End of Dosing (AUCtau) of Tocilizumab [Time Frame: Pre-infusion (Hour 0) on Days 1, 15, 29, 43, 57, 71, and 85; at the end of infusion on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 (infusion length = 1 hour)]

Secondary Outcome(s)

Number of Participants With Adverse Events (AEs) and Serious AEs [Time Frame: Baseline up to end of the study (up to approximately 60 weeks)]

Secondary ID(s)

NP25737

2015-000435-33

Source(s) of Monetary Support

Please refer to primary and secondary sponsors