Juvenile Idiopathic ArthritisPhase 1NCT01455701
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)
A Phase 1 study testing Tocilizumab in people with Juvenile Idiopathic Arthritis, run by Hoffmann-La Roche at 20 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- Juvenile Idiopathic Arthritis
- What is being tested?
- Tocilizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 20 sitesin 8 countries
- Study dates
- 26 Oct 2012to 13 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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)
Trial locations and contacts
20 sites in 8 countries.
20 sites in 8 countries
United States9 sites
The Floating Hospital for Children at Tufts Medical Center
Boston, Massachusetts, 02111
Children's Hospital Boston Pediatric Medicine
Boston, Massachusetts, 02115
The University of Chicago;Department of Pediatrics
Chicago, Illinois, 60649
Cincinnati Children'S Hospital Medical Center; Division of Rheumatology
Cincinnati, Ohio, 45229-3039
Hackensack University Medical Center; Pediatric Rheumatology
Hackensack, New Jersey, 07601
Children's Speciality Center of Nevada
Las Vegas, Nevada, 89109
University of Louisville Research Foundation, Inc; Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, 40202
Children's Hospital Of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Children's National Medical Center; Pediatric Rheumatology
Washington D.C., District of Columbia, 20010-2970
Canada3 sites
Alberta Children'S Hospital
Calgary, Alberta, T3B 6A8
McGill University; Montreal Children's Hospital; Inflammatory, Autoimmune & Bone
Montreal, Quebec, H4A 3J1
Hospital For Sick Children
Toronto, Ontario, M5G 1X8
Poland2 sites
Uniwersytecki Szpital Kliniczny Nr 4 im. M. Konopnickiej; Oddz. Kardiolog. i Reumatolog. dla Dzieci
Lodz, 91-738
Uniwersytecki Szpital Dzieciecy w Lublinie; Oddzial Pediatrii, Chorob Pluc i Reumatologii
Lublin, 20-093
Hungary1 site
Semmelweis University; 2nd Department of Paediatrics
Budapest, 1094
Spain1 site
Hospital Universitario la Fe: Servicio de Reumatologia Pediatrica
Valencia, 46026
About this study
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)
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
- Being tested
- Tocilizumab
- Medical subject headings
- Arthritis, Juvenile
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TocilizumabDrug
Also called RoActemra, Actemra, RO4877533
Tocilizumab will be administered as indicated in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Tocilizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Baseline up to end of the study (up to approximately 60 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2011 (estimated)
- Study start26 Oct 2012
- Primary completion28 Jul 2016
- Study completion13 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Juvenile Idiopathic ArthritisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01455701
- Sponsor's protocol ID
- NP25737
- Other IDs
- 2015-000435-33, 2015
- Status last verified
- Oct 2019
- First submitted
- 18 Oct 2011
- Last updated
- 4 Nov 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 31438986
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01455701
- Acronym / sponsor ID
- NP25737
- Conditions
- Juvenile Idiopathic Arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 26 Oct 2012 (actual)
- Primary completion
- 28 Jul 2016 (actual)
- Study completion
- 13 Jul 2017 (actual)
- First posted
- 20 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tocilizumab | Experimental | Drug: TocilizumabParticipants 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. |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (18 listed)
- 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:
- 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
Key exclusion criteria (37 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TocilizumabAlso: RoActemra, Actemra, RO4877533Tocilizumab will be administered as indicated in the arm description. | Drug | Tocilizumab |
Primary outcome
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)
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
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)
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
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)
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.
1 secondary outcome
Number of Participants With Adverse Events (AEs) and Serious AEs
Time frame: Baseline up to end of the study (up to approximately 60 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
- Derived from this study: PubMed 31438986Mallalieu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
20 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tocilizumab in people with Juvenile Idiopathic Arthritis, run by Hoffmann-La Roche at 20 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, Belgium, Poland, Argentina and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01455701, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2019.