A Ph II/III Seamless, Multi-center, Randomized, Double-blind, Placebo-controlled Study of the Reduction in Signs and Symptoms and Inhibition of Structural Damage During Treatment With Tocilizumab Versus Placebo in Patients With Ankylosing Spondylitis Who Have Failed Non-steroidal Anti-inflammatory Drugs and Are naïve to TNF Antagonist Therapy NSAIDs
This study was planned as a Phase II/III seamless, multicenter, randomized, double-blind,
placebo-controlled study in patients with AS who were naïve to TNF antagonist therapy. The
study consisted of 2 parts, each preceded by a screening visit and followed by a common
open-label extension phase. Recruitment into Part 2 commenced after completion of enrollment
for Part 1.
Part 1 was designed as a Phase II study exploring the efficacy and safety of tocilizumab
therapy versus placebo. Part 1 was intended to determine whether Part 2 of the study would
continue, based on a Week 12 analysis.
Part 2 was designed to provide pivotal Phase III efficacy and safety data for tocilizumab in
patients with AS. Approximately 400 patients were to be enrolled. Once randomization into
Part 1 was complete, randomization into Part 2 of the study was to be initiated.
Based on the results of the Week 12 Part 1 analyses of the primary endpoint (ASAS20) and
secondary endpoints, and in consideration of all available safety data, a benefit/risk
assessment was made and it was decided to halt the study because of lack of overall
efficacy. Most patients did not complete the 24-week double-blind treatment period in Part
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Part 1: Percentage of Participants Achieving a 20% Improvement in Assessment in Ankylosing Spondylitis (ASAS20) at Week 12
ASAS is composed of four domains. To achieve an ASAS20 response required improvement of ≥20% and ≥ 1 unit (10 mm) in at least 3 domains and no worsening of ≥ 20 % and ≥ 1 unit (10 mm) in the remaining domain. The patient's global assessment of current disease status, measured on a 100 mm visual analog scale (VAS), from symptom-free / no AS symptoms (0) to maximum AS disease severity (100). The patient's overall assessment of the severity of spinal pain based on responses to 2 questions assessed on a 100 mm VAS, from no pain (0) to most severe pain (100). The spinal pain score is the mean of these 2 questions. The function component was measured by the Bath Ankylosing Spondylitis Functional Index (BASFI). The patient provides self-assessment of 10 questions on a 100 mm VAS. The BASFI score is the mean of these values. The inflammation component of the ASAS was determined by the mean of questions 5 and 6 of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).
Baseline and Week 12
United States: Food and Drug Administration
|Albany, Georgia 31701|
|Fountain Valley, California 92708|
|Miami, Florida 33176|
|Philadelphia, Pennsylvania 19104|
|Austin, Texas 78705|
|Flint, Michigan 48532|
|Kansas City, Kansas 66160|
|Baltimore, Maryland 21287|
|Charlotte, North Carolina|
|Charleston, South Carolina|
|Coeur D'alene, Idaho 83814|