Clinical trial NCT01734382: A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Juvenile Idiopathic Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-11-27
Enrollment: 35
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

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
* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Juvenile Arthritis Disease Activity Score (JADAS-71)
timeFrame: Part 2: Up to 52 weeks
measure: Number of Participants With Juvenile Idiopathic Arthritis (JIA) Disease Flare as Determined by JIA Core Variables in Part 2 of the Study
timeFrame: Part 2: Up to 52 weeks
measure: Number of Participants With Fever Attributable to Systemic Juvenile Idiopathic Arthritis (sJIA) in Part 2 of the Study
timeFrame: Part 2: Up to 52 weeks
Secondary outcomes:
measure: Number of Participants With at Least One Adverse Event
timeFrame: 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
measure: Serum Interleukin-6 (IL-6) Protein Concentration in Part 2 of the Study
timeFrame: 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
measure: Soluble IL-6 Receptor (sIL-6R) Protein Concentration in Part 2 of the Study
timeFrame: 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
measure: C-reactive Protein (CRP) Concentration in Part 2 of the Study
timeFrame: 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
measure: Erythrocyte Sedimentation Rate (ESR) in Part 2 of the Study
timeFrame: 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
measure: Number of Participants With Anti-TCZ Antibodies in Part 2 of the Study
timeFrame: Part 2: Up to Week 52
measure: Serum TCZ Concentration in Part 2 of the Study
timeFrame: 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
measure: Baseline Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study
timeFrame: Baseline of Part 2
measure: Change From Baseline in Childhood Health Assessment Questionnaire (CHAQ) Disability Index in Part 2 of the Study
timeFrame: 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
measure: Baseline Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study
timeFrame: Baseline of Part 2
measure: Change From Baseline in Participant's/Parent's Global Assessment of Overall Well-being Score in Part 2 of the Study
timeFrame: 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
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles; Division of Rheumatoogy
state: California
city: Cincinnati
country: United States
facility: Cincinnati Children'S Hospital Medical Center; Division of Rheumatology
state: Ohio
city: Buenos Aires
country: Argentina
facility: Hospital Gral de Niños Pedro Elizalde
city: Mendoza
country: Argentina
facility: Hospital Dr. Humberto Notti
city: Calgary
country: Canada
facility: Alberta Children'S Hospital
state: Alberta
city: Berlin
country: Germany
facility: Charité Campus; Virchow Klinikum Berlin
city: Sankt Augustin
country: Germany
facility: Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie
city: Haifa
country: Israel
facility: Rambam Medicl Center, Ruth Children Hospital
city: Kfar Sava
country: Israel
facility: Meir Medical center, Pediatrics
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Roma
country: Italy
facility: Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina
state: Lazio
city: Padova
country: Italy
facility: Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica
state: Veneto
city: Mexicali
country: Mexico
facility: Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel
city: Moscow
country: Russian Federation
facility: SI Sceintific children health center RAMS
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State; Pediatrics Medical Academy
city: Barcelona
country: Spain
facility: Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal ; Servicio de Reumatologia
city: Madrid
country: Spain
facility: Hospital de La Paz; Unidad de Reumatologia Pediatrica
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Childrens Hospital; Rheumatology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: