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

Roche

Status and phase: Terminated; Phase 3

Conditions: Spondylitis, Ankylosing

Treatments: Drug: Tocilizumab; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01209689

2009-017488-40

WA22908

Details and patient eligibility

About

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.

Enrollment: 113 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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• Traditional disease-modifying anti-rheumatic drugs (DMARDs) must be withdrawn for at least 4 weeks prior to baseline (methotrexate, sulfasalazine, and hydroxychloroquine or chloroquine may be allowed if at stable dose for at least 4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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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113 participants in 3 patient groups, including a placebo group

Tocilizumab 4 mg/kg

Experimental group

Description:

Patients received tocilizumab 4 mg/kg intravenously every 4 weeks for 24 weeks.

Treatment:

Drug: Tocilizumab

Tocilizumab 8 mg/kg

Experimental group

Description:

Patients received tocilizumab 8 mg/kg intravenously every 4 weeks for 24 weeks.

Treatment:

Drug: Tocilizumab

Placebo

Placebo Comparator group

Description:

Patients received placebo to tocilizumab intravenously every 4 weeks for 24 weeks.

Treatment:

Drug: Placebo