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Juvenile Idiopathic ArthritisPhase 4NCT01734382

A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)

A Phase 4 study testing Tocilizumab in people with Juvenile Idiopathic Arthritis, run by Hoffmann-La Roche at 19 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

PART1 Participants in Part 1 (Run-in-Phase) of study will receive tocilizumab (TCZ) (RoActemra/Actemra) 12 milligrams per kilogram (mg/kg) or 8 mg/kg intravenously (IV) every 2 weeks (Q2W) for up to 24 weeks. Read more about this study

Who is it for?
Ages 2 to 17 years
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
35 participants
Where
19 sitesin 10 countries
Study dates
10 Jun 2013to 9 Oct 2019
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 2 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • PART 1 and 2
  • Children 2 to 17 years of age inclusive at screening
  • Systemic juvenile idiopathic arthritis (sJIA) according to International League of Associations for Rheumatology (ILAR) classification (2001) and sJIA symptoms lasting for at least 1 month since diagnosis of sJIA
  • Must meet one of the following:
  • Not receiving methotrexate (MTX) or discontinued MTX at least 4 weeks prior to baseline visit, or
  • Taking MTX for at least 12 weeks immediately prior to the baseline visit and on a stable dose of less than or equals (</=) 20 milligrams per meter square (mg/m^2) for at least 8 weeks prior to the baseline visit, together with either folic acid or folinic acid according to local standard of care
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  • Participants entering Part 1 who are naive to TCZ therapy must also meet the following inclusion criterion:
  • History of inadequate clinical response (in the opinion of the treating physician) to Non steroidal Anti-Inflammatory Drugs (NSAIDs) and corticosteroids PART 2
  • Juvenile Arthritis Disease Activity Score (JADAS) -71 score of 3.8 or less and absence of fever (related to sJIA) at screening and baseline
  • Neutropenia, thrombocytopenia, or elevated Alanine transaminase/Aspartate transaminase (ALT/AST) previously experienced on the labeled dose (Q2W) of RoActemra/Actemra at any time
  • Not currently receiving oral corticosteroids, or taking oral corticosteroids at a stable dose for a minimum of 2 weeks prior to baseline visit at no more than 10 milligrams per day (mg/day) or 0.2 miiligrams per kilogram per day (mg/kg/day), whichever is less
  • Not taking (NSAIDs), or taking no more than 1 type of NSAID at a stable dose for a minimum of 2 weeks prior to the baseline visit, with the dose being less than or equal to the maximum recommended daily dose

Who cannot join

  • Wheelchair bound or bedridden
  • Any other auto-immune, rheumatic disease, or overlap syndrome other than sJIA
  • Pregnant or lactating, or intending to become pregnant during study conduct and up to 6 months after the last administration of study drug
  • 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 TCZ infusion, and/or presence of anti-TCZ antibodies at screening
  • Inborn conditions characterized by a compromised immune system
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  • Known Human Immunodeficiency Virus (HIV) infection or other acquired forms of immune compromise
  • History of alcohol, drug, or chemical abuse within 6 months of screening
  • Evidence of serious uncontrolled concomitant diseases, including but not limited to the nervous, renal, hepatic, or endocrine systems
  • Any active acute, subacute, chronic or recurrent bacterial, viral, or systemic fungal infection
  • History of atypical tuberculosis (TB)
  • Active TB requiring treatment within 2 years prior to the screening visit
  • Positive purified protein derivative (PPD) at screening
  • 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 within 2 months of the screening visit
  • Positive for hepatitis B or hepatitis C infection
  • Chronic hepatitis, viral or pulmonary disease
  • Significant cardiac or pulmonary disease
  • History of or current cancer or lymphoma
  • Uncontrolled diabetes mellitus
  • History of or concurrent serious gastrointestinal disorders
  • History of macrophage activation syndrome (MAS) within 3 months prior to screening visit

Trial locations and contacts

19 sites in 10 countries.

19 sites in 10 countries

Israel3 sites
  • Rambam Medicl Center, Ruth Children Hospital

    Haifa, 3109601

  • Meir Medical center, Pediatrics

    Kfar Saba, 4428164

  • Schneider Children's Medical Center of Israel

    Petah Tikva, 4920235

Other trials in Israel

Spain3 sites
  • Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica

    Barcelona, 08950

  • Hospital Ramon y Cajal ; Servicio de Reumatologia

    Madrid, 28034

  • Hospital de La Paz; Unidad de Reumatologia Pediatrica

    Madrid, 28046

Other trials in Spain

United States2 sites
  • Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

    Cincinnati, Ohio, 45229-3039

  • Children's Hospital Los Angeles; Division of Rheumatoogy

    Los Angeles, California, 90027

Other trials in United States

Argentina2 sites
  • Hospital Gral de Niños Pedro Elizalde

    Buenos Aires, 1270

  • Hospital Dr. Humberto Notti

    Mendoza, 5519

Other trials in Argentina

Germany2 sites
  • Charité Campus; Virchow Klinikum Berlin

    Berlin, 13353

  • Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie

    Sankt Augustin, 53757

Other trials in Germany

Italy2 sites
  • Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica

    Padova, Veneto, 35128

  • Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

    Rome, Lazio, 00165

Other trials in Italy

Russia2 sites
  • SI Sceintific children health center RAMS

    Moscow, 119991

  • Saint-Petersburg State; Pediatrics Medical Academy

    Saint Petersburg, 194100

Other trials in Russia

Canada1 site
  • Alberta Children'S Hospital

    Calgary, Alberta, T3B 6A8

Other trials in Canada

Mexico1 site
  • Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel

    Mexicali, 21100

Other trials in Mexico

United Kingdom1 site
  • Royal Liverpool Childrens Hospital; Rheumatology

    Liverpool, L12 2AP

Other trials in United Kingdom

About this study

Official title: A Phase IV Study to Evaluate Decreased Dose Frequency in Patients With Systemic Juvenile Arthritis (SJIA) Who Experience Laboratory Abnormalities During Treatment With Tocilizumab

PART1 Participants in Part 1 (Run-in-Phase) of study will receive tocilizumab (TCZ) (RoActemra/Actemra) 12 milligrams per kilogram (mg/kg) or 8 mg/kg intravenously (IV) every 2 weeks (Q2W) for up to 24 weeks. Participants who experience a laboratory abnormality during Part 1 may be eligible to move into Part 2 of the study.

PART 2 This open-label Phase IV study will evaluate the efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of tocilizumab in reduced dose frequency in participants with adequately controlled systemic juvenile idiopathic arthritis who have experienced a laboratory abnormality on twice weekly tocilizumab dosing, that has since resolved. Participants will receive tocilizumab 12 mg/kg or 8 mg/kg intravenously every 3 weeks. After 5 consecutive infusions, participants who experience an event of neutropenia, thrombocytopenia or liver enzyme abnormality will move to every 4 weeks tocilizumab administration. Anticipated time on study treatment is 52 weeks.

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

    Participants will receive tocilizumab IV infusions of 12 mg/kg (for participants < 30 kg) or 8 mg/kg (for participants >/=30 kg) Q2W/Q3W/Q4W.

Study groups in NCT01734382
Study groupRoleWhat they receive
Part 1: Tocilizumab (TCZ) Q2WExperimentalParticipants will receive tocilizumab intravenous (IV) infusions (12 mg/kg for participants < 30 kg; 8 mg/kg for participants >/= 30 kg) once every other week (Q2W) up to 24 weeks or until occurrence of a protocol defined laboratory abnormality in Part 1 of the study.
Receives: Drug: Tocilizumab
Part 2: TCZ IV 12 mg/kg Q3W/Q4WExperimentalParticipants with weight < 30 kg will receive tocilizumab IV infusions of 12 mg/kg once every three weeks (Q3W) up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who complete 5 consecutive infusions of Q3W and have a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality will switch to tocilizumab IV infusions of 12 mg/kg once every four weeks (Q4W) up to Week 52 in Part 2 of the study.
Receives: Drug: Tocilizumab
Part 2: TCZ IV 8 mg/kg Q3W/Q4WExperimentalParticipants with weight >/= 30 kg will receive tocilizumab IV infusions of 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality as per protocol criteria. Participants who complete 5 consecutive infusions of Q3W and have a laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes as per protocol criteria, after resolution of this laboratory abnormality will switch to tocilizumab IV infusions of 8 mg/kg Q4W up to Week 52 in Part 2 of the study.
Receives: Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Juvenile Arthritis Disease Activity Score (JADAS-71)

    JADAS-71 has 4 components: Physician global assessment of disease activity on a visual analog scale (VAS) (range=0-10, left end of line=arthritis inactive, i.e., symptom-free and no arthritis symptoms; right end=arthritis very active), patient/parent global assessment of overall well-being on VAS (range=0-10, left end of line=very well, right end=very poor), normalized erythrocyte sedimentation rate (ESR) (range=0-10, If ESR is ≤20 mm/h, set to 0. If ≥120 mm/h, set to 10 mm/h. If > 20 mm/h and < 120 mm/h, apply formula: [ESR-20 mm/h]/10 mm/h), and a count of active arthritis (swelling present or pain present and limitation of motion) in 71 selected joints (range=0-71). JADAS-71 is sum of 4 component scores, range=0-101. A higher score=more arthritis disease activity. Data reported for up to Week 52 was collected in Part 2: Q3W arms: Baseline, Weeks 3,6,9,12,24,36,48 and 51; Q4W arms: Baseline, Weeks 0,4,8,12,24,36 and 40.

    Measured: Part 2: Up to 52 weeks

  2. Number of Participants With Juvenile Idiopathic Arthritis (JIA) Disease Flare as Determined by JIA Core Variables in Part 2 of the Study

    JIA flare was defined as any 3 of the 6 core outcome variables worsening by at least 30% relative to baseline visit of Part 2, with no more than 1 of the remaining variables improving by more than 30%. For the number of joints with active arthritis or the number of joints with limitation of motion a minimum worsening of at least 2 joints had to be present. If the physician global assessment (PGA) or the parent/patient global assessment were used a minimum worsening of at least 2 units on a scale from 0 to 10 had be present. For erythrocyte sedimentation rate (ESR), a worsening of at least 30% was not considered if within normal ranges. The 6 core outcome variables: PGA of disease activity, parent/patient global assessment of overall well-being, number of joints with active arthritis, number of joints with limitation of movement, ESR (measure of acute phase reaction) and functional ability determined by Childhood Health Assessment Questionnaire (CHAQ) Disability Index.

    Measured: Part 2: Up to 52 weeks

  3. Number of Participants With Fever Attributable to Systemic Juvenile Idiopathic Arthritis (sJIA) in Part 2 of the Study

    Absence of fever at screening visit was defined as a temperature measurement < 38 degree centigrades (C). Presence of fever at each study visit was defined as a temperature measurement ≥ 38 C.

    Measured: Part 2: Up to 52 weeks

Secondary outcomes (11)
  1. Number of Participants With at Least One Adverse Event

    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    Measured: Part 1 - Baseline up to 24 weeks plus 12 weeks of safety follow up; Part 2 - Baseline up to 52 weeks plus 12 weeks of safety follow up

  2. Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study

    Measured: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

  3. Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study

    Measured: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

  4. C-reactive Protein (CRP) Concentration in Part 2 of the Study

    Measured: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

  5. Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study

    Measured: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

  6. Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study

    Measured: Part 2: Up to Week 52

  7. Serum TCZ Concentration in Part 2 of the Study

    Measured: Part 2: Q3W arms: Pre-dose at Baseline, Weeks 3, 6, 9, 12, 24, 36, 48 and 51; Q4W arms: Pre-dose at Baseline, Weeks 0, 4, 8, 12, 24, 36 and 40

  8. Baseline Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study

    CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability.

    Measured: Baseline of Part 2

  9. Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study

    CHAQ- Disability Index consists of 30 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities-distributed, among a total of 30 items. Each question was rated on 4-point scale with range 0=no difficulty to 3=unable to do. To calculate overall score, participant must have a domain score in at least 6 of 8 domains. Scores were averaged to calculate CHAQ disability index, range is 0=no/minimal physical dysfunction)-3=very severe physical dysfunction, higher score indicates more disability. Negative change from baseline indicates an improvement.

    Measured: Baseline; Part 2: Q3W arm groups - Weeks 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 51; Q4W arm groups - Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40

  10. Baseline Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study

    Participant's/parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity).

    Measured: Baseline of Part 2

  11. Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study

    Participant's/Parent's global assessment of overall well-being was determined on a VAS (range = 0-100, left end of the line = very well, i.e., symptom-free and no arthritis disease activity; right end = very poor, i.e., maximum arthritis disease activity). Reported is the change from baseline in VAS score with a negative change from baseline indicating an improvement.

    Measured: Baseline; Part 2: Q3W arm groups - Weeks 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48 and 51; Q4W arm groups - Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36 and 40

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2012 (estimated)
  2. Study start10 Jun 2013
  3. Primary completion9 Oct 2019
  4. Study completion9 Oct 2019

Resources

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 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01734382
Sponsor's protocol ID
WA28029
Other IDs
2012-000444-10
Status last verified
Apr 2020
First submitted
22 Nov 2012
Last updated
24 Apr 2020
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tocilizumab in people with Juvenile Idiopathic Arthritis, run by Hoffmann-La Roche at 19 sites in 10 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 12 inclusion and 22 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 24 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Israel, Spain, United States, Argentina, Germany and 5 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Juvenile Arthritis Disease Activity Score (JADAS-71) (time frame: Part 2: Up to 52 weeks). 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?
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 24 Apr 2020.

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