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

Phase 1

• Conditions: 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]

• Registration Number: EUCTR2012-000444-10-GB
• Lead Sponsor: F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-08-21
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 43

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified