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)

NCT ID: NCT01455701

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-26
• Study Completion Date: 2017-07-13

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tocilizumab

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.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Tocilizumab will be administered as indicated in the arm description.

Interventions

Tocilizumab

Tocilizumab will be administered as indicated in the arm description.

Intervention Type: DRUG

Other Intervention Names

RoActemra; Actemra; RO4877533

Eligibility 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

• 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

• 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
• 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)

• Maximum Eligible Age: 24 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Children's National Medical Center; Pediatric Rheumatology

Washington D.C., District of Columbia, United States

The University of Chicago;Department of Pediatrics

Chicago, Illinois, United States

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

Louisville, Kentucky, United States

The Floating Hospital for Children at Tufts Medical Center

Boston, Massachusetts, United States

Children's Hospital Boston Pediatric Medicine

Boston, Massachusetts, United States

Children's Speciality Center of Nevada

Las Vegas, Nevada, United States

Hackensack University Medical Center; Pediatric Rheumatology

Hackensack, New Jersey, United States

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, United States

Children's Hospital Of Pittsburgh

Pittsburgh, Pennsylvania, United States

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, , Argentina

UZ Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Alberta Children'S Hospital

Calgary, Alberta, Canada

Hospital For Sick Children

Toronto, Ontario, Canada

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

Montreal, Quebec, Canada

Klinik Bremen-Mitte; Prof. Hess-Kinderklinik

Bremen, , Germany

Semmelweis University; 2nd Department of Paediatrics

Budapest, , Hungary

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

Lodz, , Poland

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

Lublin, , Poland

Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica

Valencia, , Spain

Countries

United States; Argentina; Belgium; Canada; Germany; Hungary; Poland; Spain

References

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.

Reference Type: DERIVED

PMID: 31438986 (View on PubMed)

Other Identifiers

2015-000435-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP25737

Identifier Type: -

Identifier Source: org_study_id