A Study of Tocilizumab (RoActemra/Actemra) in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous Tumor Necrosis Factor (TNF) Antagonist Therapy

Spondylitis, Ankylosing Clinical Trial

Official title:

A Randomized, Double-blind, Parallel Group Placebo-controlled Study of the Safety and Reduction of Signs and Symptoms During Treatment With Tocilizumab (TCZ) Versus Placebo in Patients With Ankylosing Spondylitis Who Have Had an Inadequate Response to Previous TNF Antagonist Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01209689
• Other study ID #: WA22908
• Secondary ID: 2009-017488-40
• Status: Terminated
• Phase: Phase 3
• First received: September 24, 2010
• Last updated: December 11, 2012
• Start date: October 2010
• Est. completion date: December 2011

Study information

• Verified date: December 2012
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This randomized, double-blind, placebo-controlled study evaluated the safety and efficacy of tocilizumab (RoActemra/Actemra) in patients with ankylosing spondylitis (AS) who had an inadequate response to previous tumor necrosis factor (TNF) antagonist therapy. Patients were randomized to receive tocilizumab at a dose of either 8 mg/kg or 4 mg/kg intravenously (iv) or placebo every 4 weeks for 24 weeks. The double-blind treatment period was followed by open-label treatment with tocilizumab 8 mg/kg iv every 4 weeks until Week 104 for all patients.

This study and all further clinical development of tocilizumab AS was halted after a review of 12-week data from Study NA22823, a randomized double-blind, placebo-controlled study in TNF antagonist naïve AS patients, failed to demonstrate efficacy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 113
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients = 18 years of age.

• Ankylosing spondylitis as defined by the modified New York criteria for = 3 months prior to baseline.

• Active disease at screening and baseline (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] = 4.0, spinal pain visual analog scale [VAS] = 40).

• Inadequate response or intolerant to 1 or more previous non-steroidal anti-inflammatory drugs (NSAIDs).

• Inadequate response to treatment with etanercept, infliximab, adalimumab, or golimumab because of inadequate efficacy.

• Tumor necrosis factor (TNF) antagonist therapy must have been discontinued at least 8 weeks prior to baseline (etanercept 4 weeks).

• Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine, and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4 weeks prior to baseline).

• Oral corticosteroids (= 10 mg/day prednisone or equivalent) and NSAIDs/cyclooxygenase-2 [COX-2] inhibitors must be at stable dose for at least 4 weeks prior to baseline.

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after randomization.

• Total ankylosis of spine (as determined by investigator).

• Inflammatory rheumatic disease other than ankylosing spondylitis.

• Active, acute uveitis at baseline.

• Previous treatment with tocilizumab.

• Intra-articular or tendon injections or parenteral corticosteroids within 4 weeks prior to screening.

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.

• Active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infection.

• History of or currently active primary or secondary immunodeficiency.

• Body weight > 150 kg.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Spondylitis
• Spondylitis, Ankylosing

Intervention

Drug:
• Tocilizumab

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Czech Republic,  Denmark,  France,  Germany,  India,  Italy,  Lithuania,  Netherlands,  Poland,  Slovakia,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of ASsessment in Ankylosing Spondylitis 20 (ASAS20) Responders at Week 12	ASAS20 was defined as an improvement of = 20% and an absolute improvement of = 10 units on a 0-100 visual analog scale (VAS) from Baseline to Week 12 in 3 of 4 domains: 1-Patient global assessment (with extremes labelled none and severe), 2-Pain assessment (average total and nocturnal pain scores with extremes labelled no pain and most severe pain), 3-Function (represented by the Bath Ankylosing Spondylitis (BAS) Functional Index [BASFI] average of 10 questions regarding ability to perform specific tasks with extremes labelled easy and impossible), and 4-Inflammation (average of the last 2 questions on the 6-question BAS Disease Activity Index [BASDAI] concerning morning stiffness intensity with extremes labelled none and very severe and duration between 0 and 2 or more hours); and the absence of deterioration (of at least 20% and absolute change of at least 10 units on a 0-100 mm scale) in the remaining domain.	Baseline to Week 12	No