Trial record 20 of 46 for:    Open Studies | "Arthritis, Juvenile Rheumatoid"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01734382
First received: November 22, 2012
Last updated: July 1, 2016
Last verified: July 2016
  Purpose

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 RoActemra/Actemra (tocilizumab) in reduced dose frequency in participants with adequately controlled systemic juvenile idiopathic arthritis who have experienced a laboratory abnormality on twice weekly RoActemra/Actemra dosing, that has since resolved. Participants will receive RoActemra/Actemra 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 RoActemra/Actemra administration. Anticipated time on study treatment is 52 weeks.


Condition Intervention Phase
Juvenile Idiopathic Arthritis
Drug: Tocilizumab
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of participants with fever (attributable to sJIA) in part 2 of the study [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Number of participants with adverse events [ Time Frame: Approximately 3 years ] [ Designated as safety issue: No ]
  • Juvenile arthritis disease activity score (JADAS-71) at the end of Part 2 of the study [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Number of Participants with juvenile idiopathic arthritis (JIA) disease flare, as determined by JIA core variables [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the curve from time zero to end of dosing interval (AUCtau) in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12, 24, 36, and 48; post-dose on Weeks 0, 3, 6, 9 and anytime on Weeks 1, 2, 10 and 11; Q4W: Pre-dose at Weeks 0, 4, 8, and 12; post-dose on Weeks 0, 4, 8 and anytime on Weeks 1, 2, 3 9, 10, and 11 ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12, 24, 36, and 48; post-dose on Weeks 0, 3, 6, 9 and anytime on Weeks 1, 2, 10 and 11; Q4W: Pre-dose at Weeks 0, 4, 8, and 12; post-dose on Weeks 0, 4, 8 and anytime on Weeks 1, 2, 3 9, 10, and 11 ] [ Designated as safety issue: No ]
  • Minimum observed plasma trough concentration (Cmin) in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12, 24, 36, and 48; post-dose on Weeks 0, 3, 6, 9 and anytime on Weeks 1, 2, 10 and 11; Q4W: Pre-dose at Weeks 0, 4, 8, and 12; post-dose on Weeks 0, 4, 8 and anytime on Weeks 1, 2, 3 9, 10, and 11 ] [ Designated as safety issue: No ]
  • Soluble IL-6 receptor (sIL-6R) protein concentration in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12, 24, 36, and 48; post-dose on Weeks 0, 3, 6, 9 and anytime on Weeks 1, 2, 10 and 11; Q4W: Pre-dose at Weeks 0, 4, 8, and 12; post-dose on Weeks 0, 4, 8 and anytime on Weeks 1, 2, 3 9, 10, and 11 ] [ Designated as safety issue: No ]
  • C-reactive protein (CRP) concentration in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12 and anytime on Weeks 1, 2, 10, and 11; Q4W: Pre-dose at Weeks 0, 4, 8, 12 and anytime on Weeks 1, 2, 3, 9, 10 and 11 ] [ Designated as safety issue: No ]
  • ESR in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12 and anytime on Weeks 1, 2, 10, and 11; Q4W: Pre-dose at Weeks 0, 4, 8, 12 and anytime on Weeks 1, 2, 3, 9, 10 and 11 ] [ Designated as safety issue: No ]
  • Number of participants with anti-TCZ antibodies in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 6, 12, 24, 36 and 48; Q4W: Pre-dose at Weeks 0, 8 and 12 ] [ Designated as safety issue: No ]
  • Change from baseline in JIA component score of participant/parent global assessment of overall well-being in part 2 of the study [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Change from baseline in JIA component score of childhood health assessment questionnaire (CHAQ) in part 2 of the study [ Time Frame: Baseline to Week 52 ] [ Designated as safety issue: No ]
  • Serum interleukin-6 (IL-6) protein concentration in part 2 of the study [ Time Frame: Q3W: Pre-dose at Weeks 0, 3, 6, 9, 12, 24, 36, and 48; post-dose on Weeks 0, 3, 6, 9 and anytime on Weeks 1, 2, 10 and 11; Q4W: Pre-dose at Weeks 0, 4, 8, and 12; post-dose on Weeks 0, 4, 8 and anytime on Weeks 1, 2, 3 9, 10, and 11 ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: June 2013
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab (RoActemra/Actemra) Q2W
Participants will receive tocilizumab IV infusions of 12 mg/kg or 8 mg/kg Q2W up to 24 weeks or until occurrence of laboratory abnormalities.
Drug: Tocilizumab
Participants will receive tocilizumab IV infusions of 12 mg/kg (for participants less than [<] 30 kg) or 8 mg/kg (for participants </=30 kg) Q2W/Q3W/Q4W.
Other Name: RoActemra/Actemra
Experimental: Tocilizumab (RoActemra/Actemra) Q3W
Participants who meets eligibility criteria for Part 2 will receive tocilizumab IV infusions of 12 mg/kg or 8 mg/kg Q3W up to 52 weeks or until occurrence of neutropenia, thrombocytopenia, or liver enzyme abnormality.
Drug: Tocilizumab
Participants will receive tocilizumab IV infusions of 12 mg/kg (for participants less than [<] 30 kg) or 8 mg/kg (for participants </=30 kg) Q2W/Q3W/Q4W.
Other Name: RoActemra/Actemra
Experimental: Tocilizumab (RoActemra/Actemra) Q4W
Participants who completed 5 consecutive infusions of Q3W and had laboratory abnormality of neutropenia, thrombocytopenia or elevated liver enzymes, will receive tocilizumab IV infusions of 12 mg/kg or 8 mg/kg Q4W up to 12 weeks.
Drug: Tocilizumab
Participants will receive tocilizumab IV infusions of 12 mg/kg (for participants less than [<] 30 kg) or 8 mg/kg (for participants </=30 kg) Q2W/Q3W/Q4W.
Other Name: RoActemra/Actemra

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01734382

Contacts
Contact: Reference Study ID Number: WA28029 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
Argentina
Completed
Buenos Aires, Argentina, 1270
Not yet recruiting
Mendoza, Argentina
Canada, Alberta
Recruiting
Calgary, Alberta, Canada, T3B 6A8
Canada, Ontario
Terminated
Ottawa, Ontario, Canada, K1H 8L1
Germany
Recruiting
Berlin, Germany, 13353
Terminated
Frankfurt/Main, Germany, 60316
Completed
Sankt Augustin, Germany, 53757
Israel
Not yet recruiting
Haifa, Israel, 3109601
Not yet recruiting
Kfar Sava, Israel, 4428164
Not yet recruiting
Petach Tikva, Israel, 4920235
Not yet recruiting
Ramat Gan, Israel, 5262100
Italy
Recruiting
Roma, Lazio, Italy, 00165
Recruiting
Genova, Liguria, Italy, 16147
Recruiting
Padova, Veneto, Italy, 35128
Mexico
Not yet recruiting
Mexicali, Mexico, 21100
Terminated
Mexico City, Mexico, 06720
Terminated
Miexico City, Mexico, 06700
Russian Federation
Not yet recruiting
Moscow, Russian Federation, 119991
Not yet recruiting
Saint-Petersburg, Russian Federation, 194100
Spain
Not yet recruiting
Esplugues De Llobregas, Barcelona, Spain, 08950
Completed
Madrid, Spain, 28034
Recruiting
Madrid, Spain, 28046
Sweden
Recruiting
Stockholm, Sweden, SE-171 76
United Kingdom
Recruiting
Liverpool, United Kingdom, L12 2AP
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01734382     History of Changes
Other Study ID Numbers: WA28029  2012-000444-10 
Study First Received: November 22, 2012
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Juvenile
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 21, 2016