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

NCT01734382 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: WA280292012-000444-10
• Study Type: interventional
• Target: 35
• Locations: 10 countries
• Sites: 19

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

Outcome Measures

Primary Outcomes (3)

• 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.

  Part 2: Up to 52 weeks

• 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.

  Part 2: Up to 52 weeks

• 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.

  Part 2: Up to 52 weeks

Secondary Outcomes (11)

• Number of Participants With at Least One Adverse Event

  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

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

  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

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

  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

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

  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

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

  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

Study Arms (3)

Part 1: Tocilizumab (TCZ) Q2W

EXPERIMENTAL

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.

Drug: Tocilizumab

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

EXPERIMENTAL

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.

Drug: Tocilizumab

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

EXPERIMENTAL

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.

Drug: Tocilizumab

Interventions

Tocilizumab 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.

Also known as: RoActemra/Actemra

Part 1: Tocilizumab (TCZ) Q2W; Part 2: TCZ IV 12 mg/kg Q3W/Q4W; Part 2: TCZ IV 8 mg/kg Q3W/Q4W

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (19)

Children's Hospital Los Angeles; Division of Rheumatoogy

Los Angeles, California, 90027, United States

Location

Cincinnati Children'S Hospital Medical Center; Division of Rheumatology

Cincinnati, Ohio, 45229-3039, United States

Location

Hospital Gral de Niños Pedro Elizalde

Buenos Aires, 1270, Argentina

Location

Hospital Dr. Humberto Notti

Mendoza, 5519, Argentina

Location

Alberta Children'S Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Charité Campus; Virchow Klinikum Berlin

Berlin, 13353, Germany

Location

Asklepios Klinik; Zentrum für Allgemeine Pädiatrie und Neonatologie

Sankt Augustin, 53757, Germany

Location

Rambam Medicl Center, Ruth Children Hospital

Haifa, 3109601, Israel

Location

Meir Medical center, Pediatrics

Kfar Saba, 4428164, Israel

Location

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235, Israel

Location

Irccs Ospedale Pediatrico Bambin Gesu - Dip. Di Medicina

Rome, Lazio, 00165, Italy

Location

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

Padua, Veneto, 35128, Italy

Location

Unidad de Reumatologia Rehabilitacion Integral; Centro Medico Del Angel

Mexicali, 21100, Mexico

Location

SI Sceintific children health center RAMS

Moscow, 119991, Russia

Location

Saint-Petersburg State; Pediatrics Medical Academy

Saint Petersburg, 194100, Russia

Location

Hospital Sant Joan De Deu; Servicio de Reumatologia Pediatrica

Barcelona, 08950, Spain

Location

Hospital Ramon y Cajal ; Servicio de Reumatologia

Madrid, 28034, Spain

Location

Hospital de La Paz; Unidad de Reumatologia Pediatrica

Madrid, 28046, Spain

Location

Royal Liverpool Childrens Hospital; Rheumatology

Liverpool, L12 2AP, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Juvenile

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2012
• First Posted: November 27, 2012
• Study Start: June 10, 2013
• Primary Completion: October 9, 2019
• Study Completion: October 9, 2019
• Last Updated: April 24, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-04

Locations

IT (2); AR (2); GB (1); DE (2); IL (3); ME (1); RU (2); CA (1); US (2); ES (3)