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)

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Completed

CT.gov ID

NCT01455701

Collaborator

(none)

Enrollment

Locations

Arm

56.5

Actual Duration (Months)

0.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Tocilizumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

11 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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)

Actual Study Start Date :

Oct 26, 2012

Actual Primary Completion Date :

Jul 28, 2016

Actual Study Completion Date :

Jul 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Tocilizumab Tocilizumab will be administered as indicated in the arm description. Other Names: RoActemra Actemra RO4877533

Arm

Intervention/Treatment

Experimental: 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.

Drug: Tocilizumab

Tocilizumab will be administered as indicated in the arm description.

Other Names:

RoActemra

Actemra

RO4877533

Outcome Measures

Primary Outcome Measures

Maximum Serum Concentration (Cmax) of Tocilizumab [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)]
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.
Minimum Serum Concentration (Cmin) of Tocilizumab [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)]
Pharmacokinetic profile of tocilizumab is evaluated in terms of observed Cmin at day 85. Pharmacokinetic-evaluable population.
Model predicted Area Under the Serum Concentration-Time Curve from Time Zero to End of Dosing (AUCtau) of Tocilizumab [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)]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 24 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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 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:

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
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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Medical Center; Pediatric Rheumatology	Washington	District of Columbia	United States	20010-2970
2	The University of Chicago;Department of Pediatrics	Chicago	Illinois	United States	60649
3	University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
4	The Floating Hospital for Children at Tufts Medical Center	Boston	Massachusetts	United States	02111
5	Children's Hospital Boston Pediatric Medicine	Boston	Massachusetts	United States	02115
6	Children's Speciality Center of Nevada	Las Vegas	Nevada	United States	89109
7	Hackensack University Medical Center; Pediatric Rheumatology	Hackensack	New Jersey	United States	07601
8	Cincinnati Children'S Hospital Medical Center; Division of Rheumatology	Cincinnati	Ohio	United States	45229-3039
9	Children's Hospital Of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
10	Hospital Gral de Niños Pedro Elizalde	Buenos Aires		Argentina	1270
11	UZ Gent	Gent		Belgium	9000
12	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
13	Alberta Children'S Hospital	Calgary	Alberta	Canada	T3B 6A8
14	Hospital For Sick Children	Toronto	Ontario	Canada	M5G 1X8
15	McGill University; Montreal Children's Hospital; Inflammatory, Autoimmune & Bone	Montreal	Quebec	Canada	H4A 3J1
16	Klinik Bremen-Mitte; Prof. Hess-Kinderklinik	Bremen		Germany	28177
17	Semmelweis University; 2nd Department of Paediatrics	Budapest		Hungary	1094
18	Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci	Lodz		Poland	91-738
19	Uniwersytecki Szpital Dzieciecy w Lublinie; Oddzial Pediatrii, Chorob Pluc i Reumatologii	Lublin		Poland	20-093
20	Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica	Valencia		Spain	46026

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hoffmann-La Roche

ClinicalTrials.gov Identifier:

NCT01455701

Other Study ID Numbers:

NP25737
2015-000435-33

First Posted:

Oct 20, 2011

Last Update Posted:

Nov 4, 2019

Last Verified:

Oct 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Arthritis

Arthritis, Juvenile

Study Results

No Results Posted as of Nov 4, 2019