Clinical trial NCT01662063: A Long-Term Extension Study of WA22762 and NA25220 of Subcutaneous (SC) Tocilizumab (TCZ) in Moderate to Severe Rheumatoid Arthritis (RA)
Official title: A Multicenter Open-Label, Long-Term Extension Study of WA22762 and NA25220 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Patients With Moderate to Severe Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-08-10
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This open-label extension study will evaluate the long-term safety and efficacy of SC TCZ in participants with moderate to severe RA who have completed the 97-week WA22762 (NCT01194414) or 96-week NA25220 (NCT01232569) core studies on SC or intravenous (IV) TCZ. Participants will receive TCZ 162 milligrams (mg) SC every week (QW) or every 2 weeks (Q2W) for up to 96 weeks.


Eligibility criteria: Inclusion Criteria:

* Completed the 97-week WA22762 (NCT01194414) or 96-week NA25220 (NCT01232569) core study on SC or IV TCZ and, based on the Investigator's judgment, may continue to benefit from TCZ treatment in this study investigating the SC formulation
* Receiving treatment on an outpatient basis
* Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception as defined by protocol

Exclusion Criteria:

* Premature withdrawal from WA22762 (NCT01194414) or NA25220 (NCT01232569) core studies for any reason
* History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
* Evidence of serious uncontrolled concomitant disease or disorder
* Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
* Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
* History of or currently active primary or secondary immunodeficiency
* Oral corticosteroids at greater than (\>) 10 mg per day prednisone or equivalent, or non-steroidal anti-inflammatory drugs (NSAIDs) above the maximum recommended dose
* Intra-articular or parenteral corticosteroids within 4 weeks prior to Baseline
* Treatment with any investigational or commercially available biologic disease-modifying anti-rheumatic drug (DMARD) other than TCZ at any time between completion of the core study WA22762 (NCT01194414) or NA25220 (NCT01232569) and enrollment in the long-term extension study
* Pregnant or breastfeeding women
* History of alcohol, drug, or chemical abuse within 1 year prior to Screening

Primary outcomes:
measure: Number of Participants With at Least One Serious Adverse Event (SAE)
timeFrame: From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)
measure: Percentage of Participants With at Least One SAE
timeFrame: From Baseline to 8 weeks after last dose; assessed continuously during treatment (up to 96 weeks) and up to 8 weeks after last dose (up to 2 years overall)
measure: Percentage of Participants With a Positive Anti-TCZ Antibody Assay at Any Timepoint
timeFrame: From Baseline to 8 weeks after last dose; assessed at Baseline; Weeks 12, 24, 36, 48, 60, 72, 84, 96; and up to 8 weeks after last dose (up to 2 years overall)
measure: Percentage of Participants With a Positive Anti-TCZ Antibody Assay at Baseline
timeFrame: Baseline
measure: Percentage of Participants With a Positive Anti-TCZ Antibody Assay Post-Baseline
timeFrame: From Week 12 up to 8 weeks after last dose; assessed at Weeks 12, 24, 36, 48, 60, 72, 84, 96; and up to 8 weeks after last dose (up to 2 years overall)
Secondary outcomes:
measure: Percentage of Participants Who Correctly Administered All SC TCZ Doses
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Disease Activity Score Based on 28 Joints (DAS28) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in DAS28 Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Clinical Disease Activity Index (CDAI) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in CDAI Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Simplified Disease Activity Index (SDAI) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in SDAI Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Tender Joint Count (TJC) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in TJC Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Swollen Joint Count (SJC) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in SJC Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Number of Participants With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Dose Reduction, Interruption, or Discontinuation
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Participants With a DMARD Dose Reduction, Interruption, or Discontinuation
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Reasons Given for DMARD Dose Reduction or Interruption
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Reasons Given for DMARD Discontinuation
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Number of Participants With a Corticosteroid (CCS) Dose Reduction, Interruption, or Discontinuation
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Participants With a CCS Dose Reduction, Interruption, or Discontinuation
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Reasons Given for CCS Dose Reduction
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Reasons Given for CCS Dose Interruption
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Reasons Given for CCS Discontinuation
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Number of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Percentage of Participants Who Switched From the QW Regimen and Remained on the Q2W Regimen
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Number of Participants Who Returned to the QW Regimen After Switching to the Q2W Regimen
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Time to Return to the QW Regimen After Switching to the Q2W Regimen
timeFrame: From Baseline to last dose; assessed every 4 weeks during treatment (up to 96 weeks overall)
measure: Global Assessment of Disease Activity by the Participant According to Visual Analog Scale (VAS) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in Global Assessment of Disease Activity by the Participant According to VAS Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Global Assessment of Pain by the Participant According to VAS Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in Global Assessment of Pain by the Participant According to VAS Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Heath Assessment Questionnaire-Disability Index (HAQ-DI) Score
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Change From Baseline in HAQ-DI Score
timeFrame: Baseline to Weeks 12, 24, 36, 48, 60, 72, 84
measure: Percentage of Participants With HAQ-DI Score <0.5
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Number of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Percentage of Participants With Low Disease Activity According to DAS28, SDAI, and CDAI Criteria
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Number of Participants With Remission According to DAS28, SDAI, and Boolean Criteria
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
measure: Percentage of Participants With Remission According to DAS28, SDAI, and Boolean Criteria
timeFrame: Baseline and Weeks 12, 24, 36, 48, 60, 72, 84
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
state: Alabama
city: Peoria
country: United States
state: Arizona
city: Scottsdale
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Fullerton
country: United States
state: California
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Leandro
country: United States
state: California
city: Upland
country: United States
state: California
city: Van Nuys
country: United States
state: California
city: West Hills
country: United States
state: California
city: Whittier
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Bridgeport
country: United States
state: Connecticut
city: Trumbull
country: United States
state: Connecticut
city: Jupiter
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: South Miami
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Venice
country: United States
state: Florida
city: Gainesville
country: United States
state: Georgia
city: Coeur D'alene
country: United States
state: Idaho
city: Idaho Falls
country: United States
state: Idaho
city: Meridian
country: United States
state: Idaho
city: Morton Grove
country: United States
state: Illinois
city: Springfield
country: United States
state: Illinois
city: Vernon Hills
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Monroe
country: United States
state: Louisiana
city: Hagerstown
country: United States
state: Maryland
city: Wheaton
country: United States
state: Maryland
city: Worcester
country: United States
state: Massachusetts
city: St. Claire Shores
country: United States
state: Michigan
city: Eagan
country: United States
state: Minnesota
city: Flowood
country: United States
state: Mississippi
city: Jackson
country: United States
state: Mississippi
city: Florissant
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Lincoln
country: United States
state: Nebraska
city: Lebanon
country: United States
state: New Hampshire
city: Clifton
country: United States
state: New Jersey
city: Freehold
country: United States
state: New Jersey
city: Manalapan
country: United States
state: New Jersey
city: Voorhees
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: Albany
country: United States
state: New York
city: Brooklyn
country: United States
state: New York
city: Orchard Park
country: United States
state: New York
city: Asheville
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Raleigh
country: United States
state: North Carolina
city: Wilmington
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Perrysburg
country: United States
state: Ohio
city: Toledo
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Oklahoma City
country: United States
state: Oklahoma
city: Tulsa
country: United States
state: Oklahoma
city: Bethlehem
country: United States
state: Pennsylvania
city: Duncansville
country: United States
state: Pennsylvania
city: Wyomissing
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Knoxville
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Nassau Bay
country: United States
state: Texas
city: Olympia
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Wenatchee
country: United States
state: Washington
city: Ponce
country: Puerto Rico
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kivitz A, Wallace T, Olech E, Borofsky M, Devenport J, Pei J, Michalska M. Long-Term Safety and Efficacy of Subcutaneously Administered Tocilizumab for Adult Rheumatoid Arthritis: A Multicenter Phase 3b Long-term Extension Study. Rheumatol Ther. 2016 Dec;3(2):291-304. doi: 10.1007/s40744-016-0043-1. Epub 2016 Sep 24.