Clinical trial NCT02011334: A Study Assessing the Safety and Efficacy of Subcutaneous RoActemra/Actemra Alone or in Combination With Non-biologic Antirheumatics in Rhuematoid Arthritis Patients in Latin America With Inadequate Response to Non-biologic Antirheumatic Drugs.
Official title: A MULTICENTER, OPEN LABEL STUDY TO EVALUATE EFFICACY AND SAFETY OF TOCILIZUMAB GIVEN SUBCUTANEOUSLY IN MONOTHERAPY AND IN COMBINATION WITH NON-BIOLOGIC DMARDS IN PATIENTS WITH MODERATE TO SEVERE ACTIVE RHEUMATOID ARTHRITIS IN LATIN AMERICA
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-12-13
Enrollment: 285
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multi-center, open-label, single-arm, Phase IIIb study will evaluate the safety and efficacy of subcutaneous RoActemra/Actemra alone or in combination with non-biologic disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis patients in Latin America with an inadequate response to non-biologic DMARDs.


Eligibility criteria: Inclusion Criteria:

* Patients \>/= 18 years of age.
* Patients with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
* Patients with moderate to severe RA (DAS-ESR 28 \>/= 3.2).
* Receiving non-study treatment on an outpatient basis.
* Oral corticosteroids (\</= 10 mg/day prednisone or equivalent), NSAIDs and non-biologic DMARDs are permitted if on a stable dose regimen for \>/= 4 weeks prior to Baseline.
* Inadequate response to previous non-biologic DMARD therapy.
* Use of effective contraception throughout the study as defined by protocol; female patients of childbearing potential cannot be pregnant.

Exclusion Criteria:

* Presence of clinically significant medical conditions.
* History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease that might predispose to perforation.
* Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections.
* Any infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening.
* Clinically significant findings on lab tests and/or hepatits B or C, or HIV screenings.
* Active TB requiring treatment within the previous 3 years.
* Evidence of active malignant disease, malignancies diagnosed within the previous 10 years, or breast cancer diagnosed within the previous 20 years.
* History of alcohol, drug, or chemical abuse within 1 year prior to Screening.
* Neuropathies or other conditions that might interfere with pain evaluation.
* 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, including systemic lupus erythematosis, mixed connective tissue disorder, scleroderma, polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Secondary Sjögren's syndrome with RA is permitted.
* Functional Class IV as defined by the ACR Classification of Functional Status in-Rheumatoid Arthritis (Appendix 2).
* 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.
* Previous exposure to RoActemra/Actemra (either IV or SC).
* Prior treatment with a biologic agent.
* Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening.
* Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
* Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
* Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.

Primary outcomes:
measure: Efficacy: Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) Remission Rate
timeFrame: 24 weeks
Secondary outcomes:
measure: Safety: Incidence of adverse events (AE)
timeFrame: 60 weeks
measure: Efficacy: Change in DAS28-ESR
timeFrame: From baseline to Week 52
measure: Efficacy: ACR/EULAR responses
timeFrame: 52 weeks
measure: Efficacy: Change in disease activity (CDAI/SDAI)
timeFrame: From baseline to Week 52
measure: Efficacy: Change in joint swelling/tenderness (SJC/TJC)
timeFrame: From baseline to Week 52
measure: Safety: Assessment of immunogenicity
timeFrame: 60 weeks
measure: Patient-reported outcomes
timeFrame: 60 weeks
measure: Efficacy: DAS28-ESR Remission Rate
timeFrame: 52 weeks
measure: Efficacy: Proportion of patients who maintain DAS28 Remission/LDA
timeFrame: From Week 24 to Week 52
measure: Safety: Rates of AE leading to dose modification or study withdrawal
timeFrame: 52 weeks
measure: Safety: Assessment of physical examination and vital signs
timeFrame: 52 weeks
measure: Safety: Incidence of clinically significant laboratory abnormalities following treatment
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: Buenos Aires
country: Argentina
city: C. A. B. A.
country: Argentina
city: Cordoba
country: Argentina
city: Rosario
country: Argentina
city: Goiania
country: Brazil
state: GO
city: Juiz de Fora
country: Brazil
state: MG
city: Cuiaba
country: Brazil
state: MT
city: Rio de Janeiro
country: Brazil
state: RJ
city: Porto Alegre
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Porto Alegre
country: Brazil
state: RS
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Sao Paulo
country: Brazil
state: SP
city: Bogota D.C.
country: Colombia
city: Bucaramanga
country: Colombia
city: Medellin
country: Colombia
city: Santo Domingo
country: Dominican Republic
city: Merida
country: Mexico
city: Mexico City
country: Mexico
city: Morelia
country: Mexico
city: Maracaibo
country: Venezuela
city: Punto Fijo
country: Venezuela
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Mysler E, Cardiel MH, Xavier RM, Lopez A, Ramos-Esquivel A. Subcutaneous Tocilizumab in Monotherapy or in Combination With Nonbiologic Disease-Modifying Antirheumatic Drugs in Latin American Patients With Moderate to Severe Active Rheumatoid Arthritis: A Multicenter, Phase IIIb Study. J Clin Rheumatol. 2020 Oct;26(7S Suppl 2):S180-S186. doi: 10.1097/RHU.0000000000001361.
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.