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

NCT ID: NCT01734382

Last Updated: 2020-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-10
• Study Completion Date: 2019-10-09

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.

Conditions

Juvenile Idiopathic Arthritis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Tocilizumab (TCZ) Q2W

Participants 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.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

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.

Part 2: TCZ IV 12 mg/kg Q3W/Q4W

Participants 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.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

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.

Part 2: TCZ IV 8 mg/kg Q3W/Q4W

Participants 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.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

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.

Interventions

Tocilizumab

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.

Intervention Type: DRUG

Other Intervention Names

RoActemra/Actemra

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Children's Hospital Los Angeles; Division of Rheumatoogy

Los Angeles, California, United States

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, United States

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, , Argentina

Hospital Dr. Humberto Notti

Mendoza, , Argentina

Alberta Children'S Hospital

Calgary, Alberta, Canada

Charité Campus; Virchow Klinikum Berlin

Berlin, , Germany

Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie

Sankt Augustin, , Germany

Rambam Medicl Center, Ruth Children Hospital

Haifa, , Israel

Meir Medical center, Pediatrics

Kfar Saba, , Israel

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, Italy

Univ. Di Padova - Dip. Di Pediatria - Unita' Reumatol. Pediatrica

Padua, Veneto, Italy

Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel

Mexicali, , Mexico

SI Sceintific children health center RAMS

Moscow, , Russia

Saint-Petersburg State; Pediatrics Medical Academy

Saint Petersburg, , Russia

Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica

Barcelona, , Spain

Hospital Ramon y Cajal ; Servicio de Reumatologia

Madrid, , Spain

Hospital de La Paz; Unidad de Reumatologia Pediatrica

Madrid, , Spain

Royal Liverpool Childrens Hospital; Rheumatology

Liverpool, , United Kingdom

Countries

United States; Argentina; Canada; Germany; Israel; Italy; Mexico; Russia; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2012-000444-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WA28029

Identifier Type: -

Identifier Source: org_study_id