A study to evaluate the efficacy and safety of tocilizumab subcutaneous in RA patients

• Register: EUCTR
• Last refreshed on: 22 August 2016
• Main ID: EUCTR2013-002150-79-BE
• Date of registration: 24/10/2013
• Prospective Registration: Yes
• Primary sponsor: N.V. Roche S.A.
• Public title: A study to evaluate the efficacy and safety of tocilizumab subcutaneous in RA patients
• Scientific title: TOSCARA: An open-label, single-arm study to evaluate the efficacy, safety and tolerability of tocilizumab (TCZ) subcutaneous in TCZ-naïve patients with active rheumatoid arthritis - TOSCARA
• Date of first enrolment: 16/12/2013
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002150-79
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium

Contacts

• Name: Clinical Trial Manager
• Affiliation: N.V. Roche S.A.

• Name: Clinical Trial Manager
• Affiliation: N.V. Roche S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Able and willing to give written informed consent and comply with the requirements of the study protocol.
2. Patients at least 18 years of age.
3. Patients with a diagnosis of active RA according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria.
4. Oral corticosteroids (=10 mg/day prednisone or equivalent) and nonsteroidal anti inflammatory drugs (NSAIDs; up to the maximum recommended dose) are permitted if on a stable dose regimen for =4 weeks prior to Baseline.
5. Permitted non-biologic DMARDs are allowed if at a stable dose for at least 4 weeks prior to Baseline.
6. Receiving treatment on an outpatient basis, not including TCZ.
7. Females of childbearing potential and males with female partners of childbearing potential may participate in this study only if using a reliable means of contraception (e.g., physical barrier [patient or partner], contraceptive pill or patch, spermicide and barrier, or intrauterine device) during the study. Women of childbearing potential must use effective contraception during and up to 3 months following the last dose of TCZ.
8. If female of childbearing potential, the patient must have a negative pregnancy test at Screening and Baseline visits.
9. Patients who have either responded inadequately to, or who were intolerant to, previous therapy with two or more non-biologic DMARDs, one of which is MTX, administered in an optimal way during at least 3 months. Eligible patients may also be inadequate responders to a biologic DMARD therapy.
10. Have moderate to severe RA defined as DAS28 = 3.7.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 37
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion criteria:
General:
1. Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline or during LTE period.
2. 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.
3. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis.
4. Diagnosis of juvenile idiopathic arthritis or juvenile RA and/or RA before the age of 16.
5. Prior history of or current inflammatory joint disease other than RA (e.g., gout, Lyme disease, seronegative spondyloarthropathy including reactive arthritis, psoriatic arthritis, and arthropathy of inflammatory bowel disease).
• Excluded Previous or Concomitant Therapy:
6. Exposure to TCZ (either intravenous [IV] or SC) at any time prior to Baseline.
7. Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever is longer) of Screening.
8. Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti CD19, and anti-CD20.
9. Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline.
10. Intraarticular or parenteral corticosteroids within 4 weeks prior to Baseline.
11. Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline.
12. Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
• Exclusions for General Safety:
13. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
14. Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal (GI) disease.
15. History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn’s disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose to perforation.
16. Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis [TB] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
17. 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.
18. Active TB requiring treatment within the previous 3 years. Patients should be screened for latent TB and, if positive, treated following local practice guidelines prior to initiating TCZ. Patients treated for TB with no recurrence in 3 years are permitted.
19. Current liver disease as determined by the Investigator.
20. Positive hepatitis B surface antigen or hepatitis C antibody.
21. Primary or secondary immunodeficiency (history of or currently active).
22. Evidence of active malignant disease, malignancies diagnosed within the previous 10 years (including hematological malignancies and solid tumors, except basal and squamous cell carcinoma of the skin or carc

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 17.0 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: RoActemra
Product Name: tocilizumab SC
Product Code: Ro 487-7533/F10-02
Pharmaceutical Form: Solution for injection
INN or Proposed INN: tocilizumab
CAS Number: 375823-41-9
Other descriptive name: TOCILIZUMAB
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 180-

Primary Outcome(s)

Secondary Objective: To assess the efficacy of SC TCZ monotherpay and / or in combination with methotrexate (MTX) or other non biologic DMARDS over time

To evaluate the safety and tolerability of SC TCZ monotherapy and / or in combination with MTX or other non biologic DMARDs

To evaluate the reasons for and time to corticosteroid dose reductions and / or discontinutation in a 24week study

To evaluate the quality of life, sleep, fatigue and health status

To evaluate patient satisfaction

To evaluate work disability

Objectives fo rthe long term extension period:

To further assess the efficacy, safety and tolerability of SC TCZ monotherapy and / or in combination with MTX or other non biologic DMARDs over time.

To further assess quality of life, sleep, fatigue, health status, patient satisfaction and work disability

Timepoint(s) of evaluation of this end point: Week 24

Main Objective: To assess the efficacy of subcutaneous (SC) tocilizumab (TCZ) monotherapy and/or in combination with methotrexate (MTX) or other non biologic disease modifying antirheumatic drugs (DMARDs) using change of DAS28(ESR) at Week 24.

Primary end point(s): Change in DAS28-ESR

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Up to week 24.
All efficacy measures will be followed up in all patients entering the extension phase.

Secondary end point(s): Efficacy outcome measures:
ACR response scores up to Week 24.
EULAR response criteria up to Week 24.
Change in SDAI and CDAI up to Week 24.
Change in total TJC and total SJC up to Week 24.
Proportion of patients and reasons for corticosteroid dose reductions and/or discontinuation over time in a 24-week study.
Number and percentage of patients achieving DAS28 low disease activity (LDA) (DAS28=3.2), CDAI LDA (=10.0) and SDAI LDA (=11.0) at every visit and time to LDA.
Number and percentage of patients achieving DAS28-ESR remission (<2.6)), CDAI remission (=2.8) and SDAI remission (=3.3) at every visit and time to remission.
Number and percentage of patients achieving a clinically meaningful improvement in DAS28 (reduction of at least 1.2 units) at every visit and time to clinically meaningful improvement in DAS28.
Number and percentage of patients achieving a major and minor improvement in CDAI (=13.9 and =6.7, respectively) and SDAI (=17.1 and =6.9, respectively) at every visit and time to major and minor improvement in CDAI and SDAI.
Change in individual parameters of ACR core data set over time.

Safety Outcome Measures
1. Incidence and severity of AEs, serious adverse events, and AEs of special interest over time up to Week 24.
2. Rates of AEs leading to dose modification or study withdrawal up to Week 24.
3. Assessment of physical examination and vital signs up to Week 24.
4. Incidence of clinically significant laboratory abnormalities following TCZ SC administration up to Week 24.
5. Assessment of immunogenicity following SC TCZ administration up to Week 24 and 8 weeks after last dose.

Immunogenicity Outcome Measures
Immunogenicity samples will be collected from all patients at Baseline, every 12 weeks during the study, at study completion or early withdrawal visit and at follow-up visit 8 weeks after the last dose.
Anti-TCZ antibodies, TCZ levels, and soluble IL-6 receptors are to be measured during the study. In addition, for any patients withdrawn due to hypersensitivity reaction (serious or non serious), these will be collected at the time of the event and at least 6 weeks after the last dose.
On dosing days, samples must be taken prior to dosing (trough drug levels). Samples taken on non-dosing days may be taken at any convenient time.

Patient-Reported Outcome Measures
1. Patient Global Assessment of disease activity visual analogue scale (PGA-VAS) up to week 24.
2. Patient Pain VAS up to week 24.
3. Health Assessment Questionnaire-Disability Index (HAQ-DI) up to week 24.
4. Patient compliance (patient diary cards and return records) up to week 24.
5. Patient Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) up to week 24.
6. Pittsburgh Sleep Quality Index (PSQI) questionnaire up to week 24.
7. Patient Sleep VAS up to week 24.
8. Arthritis Impact Measurement Scale-Short Form (AIMS-SF) questionnaire up to week 24.
9. Patient Fatigue VAS up to week 24.
10. Patient Satisfaction VAS up to week 24.
11. Treatment Satisfaction Questionnaire for Medication (TSQM) at Week 24.
12. Work Instability Scale for Rheumatoid Arthritis (RA-WIS) up to week 24.

Secondary ID(s)

ML28701

Source(s) of Monetary Support

N.V. Roche S.A.