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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01455701
First received: October 18, 2011
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
This is a multi-center, open label single arm study to investigate the pharmacokinetics and safety of tocilizumab (TCZ) (RoActemra/Actemra) in participants less than 2 years old with active systemic juvenile idiopathic arthritis (sJIA). Participants will receive tocilizumab infusions every 2 weeks. The anticipated time on study treatment is 12 weeks (Main evaluation period). Participants will have the option to continue TCZ treatment until participant reaches 2 years of age or up to one year from baseline, whichever is longer. An optional extension period will follow the main evaluation period.

Condition Intervention Phase
Systemic Juvenile Idiopathic Arthritis
Drug: Tocilizumab
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) of TCZ [ Time Frame: Pre-dose on Days 1, 15, 29, 43, 57, 71, and 85; post-dose on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 ] [ Designated as safety issue: No ]
  • Minimum observed plasma trough concentration (Cmin) of TCZ [ Time Frame: Pre-dose on Days 1, 15, 29, 43, 57, 71, and 85; post-dose on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 ] [ Designated as safety issue: No ]
  • Systemic Clearance (CL) of TCZ [ Time Frame: Pre-dose on Days 1, 15, 29, 43, 57, 71, and 85; post-dose on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vz/F) of TCZ [ Time Frame: Pre-dose on Days 1, 15, 29, 43, 57, 71, and 85; post-dose on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 ] [ Designated as safety issue: No ]
  • Area under the curve from time zero to end of dosing (AUCtau) of TCZ [ Time Frame: Pre-dose on Days 1, 15, 29, 43, 57, 71, and 85; post-dose on Days 1, 29 and 71; and anytime on Days 8, 36, and 78 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of participants with adverse events (AEs) [ Time Frame: Baseline up to 8 weeks after the last dose (overall up to week 60) ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: October 2012
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab
Participants will receive tocilizumab intravenous (IV) infusion of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) for up to 10 weeks (A total of 6 infusions including one at baseline visit) in main evaluation period and 12 mg/kg every Q2W from week 12 until participant reaches 2 years of age or has been treated for one year from baseline in optional extension period .
Drug: Tocilizumab
Participants will receive tocilizumab IV infusion of 12 mg/kg Q2W up to week 10 in main evaluation period and until participant reaches 2 years of age or up to one year from baseline in optional extension period.
Other Name: RoActemra/Actemra; RO4877533

  Eligibility

Ages Eligible for Study:   up to 24 Months   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Fulfills 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 participants 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 milligrams 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 auto-immune, rheumatic disease or overlap syndrome other than sJIA
  • Not fully recovered from recent surgery or less than six weeks since surgery, at the time of screening visit; or planned surgery during the study (except for myringotomy surgery, which is permitted)

General Safety Inclusion Criteria:

  • Any significant concurrent medical or surgical condition which would jeopardize the participants 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 TCZ 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-tuberculosis therapy for at least 4 weeks prior to receiving study medication and chest radiograph is negative for active tuberculosis within 6 months of screening visit consistent with local practice
  • Any major episode of infection requiring hospitalization or treatment during screening or treatment with intravenous (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 (Hgb) A1c as defined by age-specific standards

Excluded Previous or Concomitant Therapy:

  • Participation in another interventional clinical trial within the past thirty days or five serum half-lives of the investigative medication, whichever is longer
  • Previous treatment with TCZ
  • Administration of intravenous 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01455701

  Show 29 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01455701     History of Changes
Other Study ID Numbers: NP25737  2015-000435-33 
Study First Received: October 18, 2011
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 24, 2016