A Study of ARRY-371797 in Patients With Active Ankylosing Spondylitis

• Assess the efficacy of the study drug (versus placebo) in terms of Assessments in Ankylosing Spondylitis 20% Working Group response criterion (ASAS 20). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]

• Efficacy of ARRY-371797 as measured by ASAS 20 (Assessments in Ankylosing Spondylitis 20% Working Group response criterion) [ Time Frame: At Week 12 ] [ Designated as safety issue: No ]
• Safety of ARRY-371797 as measured by adverse events, findings on physical examinations, laboratory abnormalities, change from baseline in vital sign measurements, and change from baseline in 12-lead ECG parameters [ Time Frame: Duration ] [ Designated as safety issue: Yes ]

• Characterize the pharmacokinetics (PK) of the study drug and a metabolite in terms of plasma concentrations. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
• Explore potential biomarkers for pharmacodynamics (PD). [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

• Efficacy as measured by ASAS 20, ASAS 40, ASAS 5/6, BASDAI, BASFI, BASMI, EASMI, SPARCC Enthesitis Index, Nocturnal Back Pain, Total Back Pain, Patient's Global Assessment of Disease Activity, SF-36 Health Questionnaire V2 Acute, and CRP [ Time Frame: Day 1-Day 85 ] [ Designated as safety issue: No ]
• Pharmacokinetics as measured by plasma concentrations of ARRY-371797 and a metabolite [ Time Frame: Days 8, 43 and 85 ] [ Designated as safety issue: No ]
• Pharmacodynamics as measured by circulating levels of exploratory biomarkers of disease activity, and sacroiliac (SI) and spinal SPARCC MRI scores [ Time Frame: Day 1- Follow-up ] [ Designated as safety issue: No ]

This is a Phase 2 study, involving a 12-week treatment period, designed to evaluate the effectiveness of investigational study drug ARRY-371797 (versus placebo) in treating ankylosing spondylitis, and to further evaluate the drug's safety. Approximately 130 patients from the US, Canada, Poland and Hungary will be enrolled in this study.

• Drug: ARRY-371797, p38 inhibitor; oral
  multiple dose, single schedule
• Drug: Placebo; oral
  matching placebo
• Drug: Placebo; oral
  multiple dose, single schedule

• Experimental: ARRY-371797 (Schedule 1)
  Intervention: Drug: ARRY-371797, p38 inhibitor; oral
• Experimental: ARRY-371797 (Schedule 2)
  Interventions:

  • Drug: ARRY-371797, p38 inhibitor; oral
  • Drug: Placebo; oral
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo; oral

Key Inclusion Criteria:

• Diagnosis of ankylosing spondylitis according to the Modified New York Criteria (1984).
• Inadequate response to at least 2 weeks of continuous treatment with NSAIDs, or unable to receive ≥ 2 full weeks of continuous treatment with NSAIDs because of intolerance.
• If previously treated with a biological agent, patient must not have failed due to lack of efficacy, and must have completed an appropriate washout period prior to first dose of study drug.
• Patients may continue on specified stable background therapies for ankylosing spondylitis (doses should be stable for at least 4 weeks prior to the first dose of study drug).
• Additional criteria exist.

Key Exclusion Criteria:

• Diagnosis of any other active or uncontrolled inflammatory or non-inflammatory articular disease that may interfere with disease activity assessments.
• Previously treated with intravenous immunoglobulins within 6 months prior to first dose of study drug.
• Patients requiring prohibited concomitant medications including moderate or strong CYP3A inhibitors, CYP3A inducers and Biologic Response Modifiers (BRMs) while on study.
• Trauma or other major surgeries within 8 weeks prior to first dose of study drug.
• Specific abnormal laboratory values or electrocardiogram abnormalities.
• Known positive serology for human immunodeficiency virus (HIV), hepatitis C, and/or hepatitis B.
• Additional criteria exist.