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)

NCT01455701 | Completed Phase 1 FDA Drug

• 2 other identifiers: NP257372015-000435-33
• Study Type: interventional
• Target: 11
• Locations: 8 countries
• Sites: 20

Brief Summary

This is a multi-center, open-label single-arm study to investigate the pharmacokinetics and safety of tocilizumab (RoActemra/Actemra) in participants less than 2 years old with active 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 tocilizumab 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.

Conditions

Juvenile Idiopathic Arthritis

Outcome Measures

Primary Outcomes (3)

• Maximum Serum Concentration (Cmax) of Tocilizumab

  Pharmacokinetic profile of tocilizumab is evaluated in terms of model predicted Cmax at steady state. Pharmacokinetic-evaluable population includes all participants who provided at least one serum pharmacokinetic sample with valid concentration data.

  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

  Pharmacokinetic profile of tocilizumab is evaluated in terms of observed Cmin at day 85. Pharmacokinetic-evaluable population.

  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

  AUCtau is the model-predicted area under the tocilizumab serum concentration versus time curve from time zero to the end of dosing interval (2 weeks). Pharmacokinetic-evaluable population.

  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 Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious AEs

  Baseline up to end of the study (up to approximately 60 weeks)

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Participants will receive tocilizumab intravenous (IV) infusion at a dose of 12 milligrams per kilogram (mg/kg) every two weeks (Q2W) during main evaluation period of 12 weeks (a total of 6 infusions including one at baseline visit). Participants will have the option to be treated in an optional extension period after completion of main evaluation period. In optional extension period, participants will receive tocilizumab 12 mg/kg IV infusion Q2W from Week 12 until the participant reaches 2 years of age or has been treated for one year from baseline, whichever is longer.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Tocilizumab will be administered as indicated in the arm description.

Also known as: RoActemra, Actemra, RO4877533

Tocilizumab

Eligibility Criteria

• Age: Up to 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• 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
• 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:
• Etanercept must have been discontinued within \>= 2 weeks prior to baseline
• Anakinra must have been discontinued within \>= 4 days prior to baseline
• Abatacept must have been discontinued within \>= 12 weeks prior to baseline
• Infliximab or adalimumab must have been discontinued within \>= 8 weeks prior to baseline
• Canakinumab must have been discontinued within \>= 20 weeks prior to baseline
• Rilonacept must have been discontinued within \>= 6 weeks prior to baseline
• Golimumab must have been discontinued within \>= 10 weeks prior to baseline

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (20)

Children's National Medical Center; Pediatric Rheumatology

Washington D.C., District of Columbia, 20010-2970, United States

Location

The University of Chicago;Department of Pediatrics

Chicago, Illinois, 60649, United States

Location

University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit

Louisville, Kentucky, 40202, United States

Location

The Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Children's Hospital Boston Pediatric Medicine

Boston, Massachusetts, 02115, United States

Location

Children's Speciality Center of Nevada

Las Vegas, Nevada, 89109, United States

Location

Hackensack University Medical Center; Pediatric Rheumatology

Hackensack, New Jersey, 07601, United States

Location

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital Of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, 1270, Argentina

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

McGill University; Montreal Children's Hospital; Inflammatory, Autoimmune & Bone

Montreal, Quebec, H4A 3J1, Canada

Location

Klinik Bremen-Mitte; Prof. Hess-Kinderklinik

Bremen, 28177, Germany

Location

Semmelweis University; 2nd Department of Paediatrics

Budapest, 1094, Hungary

Location

Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci

Lodz, 91-738, Poland

Location

Uniwersytecki Szpital Dzieciecy w Lublinie; Oddzial Pediatrii, Chorob Pluc i Reumatologii

Lublin, 20-093, Poland

Location

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

Valencia, 46026, Spain

Location

Related Publications (1)

• Mallalieu NL, Wimalasundera S, Hsu JC, Douglass W, Wells C, Penades IC, Cuttica R, Huppertz HI, Joos R, Kimura Y, Milojevic D, Rosenkranz M, Schikler K, Constantin T, Wouters C. Intravenous dosing of tocilizumab in patients younger than two years of age with systemic juvenile idiopathic arthritis: results from an open-label phase 1 clinical trial. Pediatr Rheumatol Online J. 2019 Aug 22;17(1):57. doi: 10.1186/s12969-019-0364-z.

  PMID: 31438986 DERIVED

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2011
• First Posted: October 20, 2011
• Study Start: October 26, 2012
• Primary Completion: July 28, 2016
• Study Completion: July 13, 2017
• Last Updated: November 4, 2019

Record last verified: 2019-10

Locations

CA (3); AR (1); BE (2); US (9); DE (1); PL (2); ES (1); HU (1)