Clinical trial NCT02046616: A Study of Subcutaneous (SC) Tocilizumab (RoActemra/Actemra) in Participants With Active Rheumatoid Arthritis (RA) and Inadequate Response to Disease-Modifying Anti-Rheumatic Drugs (DMARDs)
Official title: Tocilizumab SC in Patients With Active Rheumatoid Arthritis and Inadequate Response to DMARDs. A Single-Arm, Open-Label Study to Evaluate Safety, Tolerability and Efficacy. In a Subgroup of Patients Inflammation Will Be Measured by Ultrasound.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-01-28
Enrollment: 133
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase IIIb, open-label, single-arm study will evaluate the safety, efficacy, and tolerability of SC tocilizumab (RoActemra/Actemra) in monotherapy or in combination with methotrexate or other non-biologic DMARDs in participants with active RA who are naive to tocilizumab. Participants will receive tocilizumab 162 milligrams (mg) subcutaneously weekly (QW) for 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Active RA according to the revised ACR (1987) criteria or EULAR/ACR (2010) criteria
* Moderate to severe RA with a DAS28-ESR score \>3.2 points
* Inadequate response and/or intolerance to MTX or other non-biologic DMARDs and/or where MTX or other non-biologic DMARDs are inappropriate
* Oral corticosteroids (less than or equal to \[\</=\] 10 mg per day prednisolone or equivalent) and nonsteroidal anti-inflammatory drugs (NSAIDs) permitted if on stable dose regimen for greater than or equal to \[\>/=\] 4 weeks prior to baseline
* Permitted non-biologic DMARDs allowed if at stable dose for \>/=4 weeks prior to baseline
* Receiving treatment on an outpatient basis, not including tocilizumab
* Agreement to use reliable means of contraception as defined by protocol, among females of childbearing potential and males with female partners of childbearing potential

Exclusion Criteria:

* Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
* Rheumatic autoimmune disease other than RA
* Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
* Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16
* Prior history of or current inflammatory joint disease other than RA
* Exposure to tocilizumab or any other biologic DMARDs at any time prior to baseline
* Treatment with any investigational agent within 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of screening
* Intra-articular or parenteral corticosteroids within 4 weeks prior to baseline
* History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
* Evidence of serious concomitant disease or disorder
* Known active current or history of recurrent infection
* Any major episode of infection requiring hospitalization or treatment with intravenous (IV) antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
* Active tuberculosis requiring treatment within the previous 3 years
* Positive for hepatitis B or hepatitis C
* History of or current active primary or secondary immunodeficiency
* Pregnant or lactating women
* Neuropathies or other conditions that might interfere with pain evaluation
* Inadequate hematologic, renal, or liver function

Primary outcomes:
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in Disease Activity Score 28 (DAS28)-Erythrocyte Sedimentation Rate (ESR) Score
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Percentage of Participants With American College of Rheumatology (ACR) Response
timeFrame: Weeks 2, 4, 8, 12, 16, 20, 24
measure: Percentage of Participants With European League Against Rheumatism (EULAR) Response
timeFrame: Weeks 2, 4, 8, 12, 16, 20, 24
measure: Change From Baseline in CDAI at Weeks 2, 4, 8, 16, 20, and 24
timeFrame: Baseline and Weeks 2, 4, 8, 16, 20, 24
measure: Change From Baseline in Simplified Disease Activity Index (SDAI)
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Change From Baseline in TJC
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Change From Baseline in SJC
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Percentage of Participants With At Least One Adverse Event Leading to Dosage Modification
timeFrame: Baseline up to Week 24
measure: Number of Participants With Neutralizing Anti-Tocilizumab Antibodies
timeFrame: Baseline to FU Week 8 (up to 32 weeks overall)
measure: Tocilizumab Concentration
timeFrame: Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
measure: Soluble Interleukin-6 Receptor (sIL-6R) Concentration
timeFrame: Predose (30 minutes) at baseline; Weeks 12, 24; and FU Week 8 (up to 32 weeks overall)
measure: Change From Baseline in Patient Global Assessment of Disease Activity According to VAS
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Patient Global Assessment of RA-Related Pain According to VAS
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Change From Baseline in HAQ-DI Score
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
measure: Compliance With Treatment According to Percentage of Injections Administered
timeFrame: Baseline up to Week 24
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
timeFrame: Baseline and Weeks 2, 4, 8, 12, 16, 20, 24
Other outcomes:
Locations:
city: Alborg
country: Denmark
facility: Aalborg Universitetshospital Nord, Reumatologisk Afdeling
city: Glostrup
country: Denmark
facility: Glostrup Hospital, Reumatologisk Afdeling, Ambulatoriet
city: Hellerup
country: Denmark
facility: Gentofte Hospital, Medicinsk Afd. C, Klinik for Gigt- og Rygsygdomme
city: Holbæk
country: Denmark
facility: Holbæk Sygehus, Medicinsk Afd., Reumatologisk Amb.15-2
city: Køge
country: Denmark
facility: Sjællands Universitetshospital, Køge; Reumatologisk Afdeling
city: Odense
country: Denmark
facility: Odense Universitetshospital, Reumatologisk Afdeling C, Ambulatoriet
city: Svendborg
country: Denmark
facility: Svendborg Sygehus, Reumatologisk Ambulatorium
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital; Rheumatology Clinic
city: Hyvinkää
country: Finland
facility: Kiljavan Lääketutkimus Oy
city: Joensuu
country: Finland
facility: Central Hospital of Pohjois-Karjala; Outpatient Clinic of Rheumatology
city: Jyväskylä
country: Finland
facility: Keski-Suomen Keskussairaala; Sisätautien Klinikka
city: Lappeenranta
country: Finland
facility: Lappeenranta Central Hospital; Outpatient Clinic of Internal Medicine
city: Oulu
country: Finland
facility: Oulu University Hospital; Rheumatology
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus; Revmatologisk Avdeling
city: Drammen
country: Norway
facility: Drammen sykehus Vestre Viken HF, Revmatologisk avd.
city: Oslo
country: Norway
facility: Diakonhjemmet; Reumatolgisk Avdeling
city: Trondheim
country: Norway
facility: St. Olavs Hospital; Revmatologisk avdeling
city: Ålesund
country: Norway
facility: Ålesund Sykehus; Revmatologisk Avdeling
city: Jönköping
country: Sweden
facility: Länssjukhuset Ryhov; Ortoped- och Reumatolog kliniken
city: Linkoeping
country: Sweden
facility: Uni Hospital Linkoeping; Dept. of Rheumatology
city: Lund
country: Sweden
facility: Skånes Universitetssjukhus Lund; Reumatologkliniken
city: Malmo
country: Sweden
facility: Skånes Universitetssjukhus Malmö; Reumatologkliniken
city: Oerebro
country: Sweden
facility: Örebro Uni Hospital; Rheumatology
city: Simrishamn
country: Sweden
facility: Simrishamns Sjukhus
city: Stockholm
country: Sweden
facility: Karolinska Sjukhuset; Reumatologkliniken D2-1
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Reumatologkliniken
city: Västerås
country: Sweden
facility: Västmanlands sjukhus Västerås, Reumatologkliniken
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Hammer HB, Jensen Hansen IM, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Rheumatoid arthritis patients with predominantly tender joints rarely achieve clinical remission despite being in ultrasound remission. Rheumatol Adv Pract. 2021 May 14;5(2):rkab030. doi: 10.1093/rap/rkab030. eCollection 2021.
citation: Hammer HB, Hansen I, Jarvinen P, Leirisalo-Repo M, Ziegelasch M, Agular B, Terslev L. Major reduction of ultrasound-detected synovitis during subcutaneous tocilizumab treatment: results from a multicentre 24 week study of patients with rheumatoid arthritis. Scand J Rheumatol. 2021 Jul;50(4):262-270. doi: 10.1080/03009742.2020.1845394. Epub 2021 Jan 19.
citation: Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Devenport J, Petho-Schramm A. Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis. Rheumatology (Oxford). 2019 Jun 1;58(6):1056-1064. doi: 10.1093/rheumatology/key393.
citation: Choy E, Caporali R, Xavier R, Fautrel B, Sanmarti R, Bao M, Bernasconi C, Petho-Schramm A. Subcutaneous tocilizumab in rheumatoid arthritis: findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries. Rheumatology (Oxford). 2018 Mar 1;57(3):499-507. doi: 10.1093/rheumatology/kex443.