A study to look at less frequent dosing in patients with systemic juvenile idiopathic arthritis (sJIA) who have experienced a laboratory abnormality during treatment with tocilizumab

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2012-000444-10-GB
• Date of registration: 21/08/2012
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd.
• Public title: A study to look at less frequent dosing in patients with systemic juvenile idiopathic arthritis (sJIA) who have experienced a laboratory abnormality during treatment with tocilizumab
• Scientific title: A PHASE IV STUDY TO EVALUATE DECREASED DOSE FREQUENCY IN PATIENTS WITH SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS (SJIA) WHO EXPERIENCE LABORATORY ABNORMALITIES DURING TREATMENT WITH TOCILIZUMAB
• Date of first enrolment: 09/11/2012
• Target sample size: 43
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000444-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: This is a study to look at reducing dosing frequency.; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Australia, Canada, Germany, Israel, Italy, Mexico, Norway, Russian Federation, Spain, Sweden, United Kingdom

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Part 1 and Part 2:
• Age 2 years up to and including 17 years at screening into trial
• sJIA according to International League of Associations for
Rheumatology (ILAR) classification (2001)
• sJIA symptoms lasting for at least 1 month since diagnosis of sJIA
• For female patients of reproductive potential: agreement to remain
abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at
least 6 months after the last dose of TCZ
• For male patients of reproductive potential: agreement to remain
abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of TCZ
• Patients entering Part 1 who are naïve to TCZ therapy must also meet
the following inclusion criterion:
• History of inadequate clinical response (in the opinion of
the treating physician) to NSAIDs and corticosteroids
• Must meet one of the following:
Not receiving 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 =20 mg/m2 for at least 8 weeks prior to the
baseline visit, together with either folic acid or folinic acid according to
local standard of care.

Part 2:
All patients entering Part 2 (either directly without participating in Part
1, or via Part 1) must meet the following additional criteria for entry into
Part 2:
• JADAS-71 score of 3.8 or less and absence of fever (related to sJIA) at
screening and baseline.
• Neutropenia, thrombocytopenia, or elevated ALT/AST (as per defined
criteria) previously experienced (and resolved) on the labeled dose
(Q2W) of TCZ at any time.
•Laboratory Abnormalities Serving as Inclusion Criteria for Part 2 When
Experienced (with Resolution) on Q2W TCZ
Abnormality Results Range
Neutropenia ANC 0.5 to 1.0 X 10 to the 9/L
Thrombocytopenia Platelets 50 to 100 X 10 to the 9/L
Elevated liver enzymes ALT/AST > 1 to 3 xULN

TCZ=tocilizumab; ULN=upper limit of normal.

• Not currently receiving oral corticosteroids, or taking oral
corticosteroids at a stable dose for a minimum of 2 weeks prior to the
part 2 baseline visit at no more than 10 mg/day or 0.2 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 part 2 baseline visit, with the dose being less than or equal to the maximum recommended daily dose.
Are the trial subjects under 18? yes

Exclusion criteria:
• Wheelchair bound or bedridden
• Lack of peripheral venous access.
• Any other auto-immune, 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 Part 1
and the initial 12 weeks of Part 2 of the study (for patients entering Part
1) or the initial 12 weeks of Part 2 of the study (for patients entering
Part 2 without participating in Part 1).
• Any significant concurrent medical or surgical condition which would
jeopardize the patient's safety or ability to complete the trial.
• Pregnant, lactating, or intending to become pregnant during study
conduct and up to 6 months after the last administration of study drug.
• History of significant allergic or infusion reactions to prior TCZ
infusion, and/or presence of anti-TCZ antibodies by confirmatory and/or
neutralizing assay at screening.
• Inborn conditions characterized by a compromised immune system.
• Known 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 including but not limited to:
a) Acute or chronic renal / bladder infections
b) Acute or chronic pulmonary infections

• History of atypical tuberculosis (TB)
• Active TB requiring treatment within 2 years prior to the screening
visit
• Positive purified protein derivative (PPD) at screen (or equivalent
result based on local methodology, e.g., Quantiferon gold), unless
treated with anti-TB therapy for at least 4 weeks prior to receiving study drug and chest radiograph is negative for active TB within 6 months of
screening visit according to 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
• Hepatitis B surface Antigen or hepatitis C Ab positive
• Chronic hepatitis - viral or autoimmune
• History or concurrent serious gastrointestinal (GI) disorders, such as
ulcer or inflammatory bowel disease, Crohn's disease, ulcerative colitis,
or other symptomatic lower GI conditions, including ulcer and
perforation
• Significant cardiac [e.g., congenital heart disease

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Systemic juvenile idiopathic arthritis (sJIA)
MedDRA version: 21.0 Level: PT Classification code 10059176 Term: Juvenile idiopathic arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: RoActemra
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Current Sponsor code: RO4877533
Other descriptive name: IL-6 receptor inhibitor, recombinant humanized monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Primary end point(s): Efficacy:
1.JADAS-71 will be utilized to describe efficacy in patients on Q3W and
Q4W dosing as appropriate in this study
2.JIA flare relative to baseline of Part 2 will be used to determine those
patients not maintaining efficacy who can be withdrawn from the study
at the discretion of the investigator
3.Fever (attributable to sJIA) will be measured at each study visit of Part
2 in patients on Q3W and Q4W dosing (as appropriate) to describe
efficacy and to determine patients not maintaining efficacy who can be
withdrawn from the study at the discretion of the investigator
Pharmocokinetics and Pharmacodynamic:
4.Serum IL-6 and sIL-6R levels and inflammatory markers (CRP and
erythrocyte sedimentation rate [ESR])
5.Anti-TCZ antibodies

Secondary Objective: Safety:
• To evaluate the safety of TCZ in reduced dosing frequency regimens.
Pharmacokinetic:
• To describe the pharmacokinetics of TCZ in reduced dosing frequency regimens.
Patient-Reported Outcome:
• To describe the Child Health Assessment Questionnaire (CHAQ) outcomes with TCZ in reduced dosing frequency regimens.
• To describe parent/patient global assessment of overall well-being with TCZ in reduced dosing frequency regimens.

Main Objective: Efficacy:
• To explore the efficacy of TCZ in reduced dosing frequency regimens (Q3W and Q4W, as appropriate) using Juvenile Arthritis Disease Activity Score (JADAS)-71, JIA flare, and fever (attributable to sJIA)
Pharmacodynamic:
• To describe the pharmacodynamics, using sIL-6R and C-reactive protein (CRP), and immunogenicity of TCZ in reduced dosing frequency regimens.

Timepoint(s) of evaluation of this end point: 1-5. Up to 52 weeks of Part 2.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Part 1: week 1 up to 24 weeks for safety
Part 2: Q3W up to 12 weeks or 52 weeks; Q4W 12 weeks up to 52 weeks for safety, PRO and pharmacokinetics

Secondary end point(s): Safety:
• Adverse events (including adverse events of special interest)
• Serious adverse events
• Clinical laboratory results

Pharmacokinetic:
• Serum TCZ concentration and population PK model predicted PK exposures (area under the serum concentration-time profile [AUCt], maximum concentration observed [Cmax], and minimum concentration under steady-state conditions within a dosing interval [Cmin]) for Q3W and Q4W dosing regimens as appropriate

Patient-Reported Outcome:
• The CHAQ
• Parents/patients global assessment of overall well-being

Secondary ID(s)

WA28029

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date:
Contact: