A Study of Subcutaneously Administered Tocilizumab in Patients With Rheumatoid Arthritis

Open-label, Multicenter, Randomized, Parallel Study to Investigate pk, pd, Efficacy and Safety of Tocilizumab (TCZ, RO4877533) Following Subcutaneous Administration of TCZ 162 mg Weekly or Every Other Week in Combination With Methotrexate in Patients With Rheumatoid Arthritis

This open-label randomized 2arm study will investigate the pharmacokinetics, pharmacodynamics, efficacy and safety of subcutaneously administered tocilizumab in patients with rheumatoid arthritis who have shown an inadequate response to methotrexate. Patients will be randomized to receive tocilizumab 162 mg sc either weekly or every other week, in combination with methotrexate, for 12 weeks. Assessments will be made at regular intervals during treatment and on the 3 weeks of follow-up.Target sample size is < 50 individuals.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: folic acid; Drug: methotrexate; Drug: tocilizumab [RoActemra/Actemra]; Drug: tocilizumab [RoActemra/Actemra]

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Newfoundland and Labrador
    • St John's, Newfoundland and Labrador, Canada, A1A 5E8
  • Ontario
    • Kitchener, Ontario, Canada, N2M 5N6
  • Quebec
    • Trois-rivieres, Quebec, Canada, G8Z 1Y2
• New Zealand
  • Christchurch, New Zealand, 8011
• Spain
  • Sevilla, Spain, 41009
  • La Coruña
    • La Coruna, La Coruña, Spain, 15006
    • Santiago de Compostela, La Coruña, Spain, 15706

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adults 18 - 75 years of age
• active rheumatoid arthritis of >/= 6 months duration
• inadequate response to at least 12 weeks of methotrexate, the last 8 prior to baseline on stable dose
• swollen joint count (SJC)>/=4, tender joint count (TJC)>/=6 at screening and baseline
• DMARDs and anti-TNFs, other than methotrexate, withdrawn prior to baseline
• oral corticosteroids (</= 10mg/day prednisone or equivalent) and NSAIDS on stable dose </= 4 weeks prior to baseline

Exclusion Criteria:

• rheumatic autoimmune disease other than rheumatoid arthritis
• prior history or current inflammatory joint disease other than rheumatoid arthritis
• major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following enrollment
• functional class IV by ACR classification

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 2	Drug: folic acid; >/= 5 mg po weekly; Drug: methotrexate; 7.5 - 25 mg weekly (oral or parenteral); Drug: tocilizumab [RoActemra/Actemra]; 162 mg sc weekly (QW)for 12 weeks; Drug: tocilizumab [RoActemra/Actemra]; 162 mg sc every other week (Q2W) for 12 weeks
EXPERIMENTAL: 1	Drug: folic acid; >/= 5 mg po weekly; Drug: methotrexate; 7.5 - 25 mg weekly (oral or parenteral); Drug: tocilizumab [RoActemra/Actemra]; 162 mg sc weekly (QW)for 12 weeks; Drug: tocilizumab [RoActemra/Actemra]; 162 mg sc every other week (Q2W) for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics of TCZ after QW or Q2W sc administration	multiple sampling after 1st and last dose, weeks 1 and 12, at bi-weekly intervals during treatment and twice on follow-up
Pharmacodynamic responses of CRP	sampling in weeks 1 and 2 and at weekly or bi-weekly intervals throughout treatment
Safety and tolerability, including injection site reaction	laboratory assessments every 2nd week on treatment and after 3 weeks follow-up, injection site evaluation after 1st, 2nd and last injection.

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy according to ACR and DAS-EULAR parameters	assessments on day 1 of weeks 1, 4, 8 and 12
PD responses of IL-6, sIL-6R and anti TCZ antibody	multiple sampling after 1st and last dose, weeks 1 and 12, at bi-weekly intervals during treatment and twice on follow-up

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Study Completion: July 1, 2011

Study Registration Dates

• First Submitted: August 18, 2009
• First Submitted That Met QC Criteria: August 21, 2009
• First Posted (ESTIMATE): August 25, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Micronutrients; Vitamins; Reproductive Control Agents; Vitamin B Complex; Hematinics; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Folic Acid
• Other Study ID Numbers: NP22623; 2009-011349-18