Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
Treatment With ARRY-371797 in Patients With Active Ankylosing Spondylitis
This study is currently recruiting participants.
Verified by Array BioPharma, December 2008
Sponsored by: Array BioPharma
Information provided by: Array BioPharma
ClinicalTrials.gov Identifier: NCT00811499
  Purpose

The purpose of this study is to test the safety and efficacy of ARRY-371797 in patients with ankylosing spondylitis that have not responded to conventional therapy.


Condition Intervention Phase
Ankylosing Spondylitis
Drug: ARRY-371797
Drug: Placebo
Phase II

Genetics Home Reference related topics: ankylosing spondylitis
MedlinePlus related topics: Ankylosing Spondylitis
Drug Information available for: Lactose
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase II, Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study to Investigate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of 12 Weeks of Treatment With ARRY-371797 in Patients With Active Ankylosing Spondylitis and Inadequate Response to Conventional Therapy

Further study details as provided by Array BioPharma:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 168
Study Start Date: December 2008
Estimated Study Completion Date: October 2009
Estimated Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
100 mg q12h of ARRY-371797
Drug: ARRY-371797
Drug in Capsule
2: Experimental
200 mg q12h of ARRY-371797
Drug: ARRY-371797
Drug in Capsule
3: Experimental
400 mg q24h of ARRY-371797
Drug: ARRY-371797
Drug in Capsule
4: Placebo Comparator
Placebo
Drug: Placebo
Lactose monohydrate in capsule

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has provided written informed consent and is willing to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures;
  2. Is at least 18 years of age;
  3. Diagnosed with ankylosing spondylitis according to the Modified New York Criteria (1984);
  4. Total Back Pain Score measured by 10-point numerical rating scale (NRS) ≥ 4 at Screening and at Baseline;
  5. Clinically active axial disease characterized by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4 at Screening and at Baseline despite concurrent treatment with conventional therapy (e.g., NSAIDs, glucocorticoids or DMARDs);
  6. 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;
  7. If previously treated with a biological agent [etanercept (Enbrel®), infliximab (Remicade®), adalimumab (Humira®), anakinra (Kineret®)], must NOT have failed due to lack of efficacy, and has completed a 3-month washout period (calculated from first dose of Study Drug);
  8. Has completed a 4-week washout period (calculated from first dose of Study Drug), if treated with any of the following therapies:

    1. Any experimental therapy (within or outside a clinical trial setting);
    2. Intramuscular or intravenous corticosteroids;
    3. Other—herbal medications; immunization with any live virus vaccination (e.g., FluMist®).
  9. Patients may continue on stable background therapy for AS (doses should be stable for at least 4 weeks prior to the first dose of Study Drug) only if it is included in the following list:

    1. Non-investigational NSAIDs and/or COX-2 inhibitors;
    2. DMARDs—methotrexate (≤ 25 mg/week), sulfasalazine (≤ 3 gm/day), leflunomide (≤ 20 mg/day);
    3. Hydroxychloroquine (≤ 400 mg/day);
    4. Low-dose oral corticosteroids (≤ 10 mg prednisone or equivalent per day);
    5. Opioid analgesics (≤ 30 mg oral morphine or equivalent per day);
    6. Acetaminophen (paracetamol) ≤ 2600 mg/day (2.6 g/day);
    7. Aspirin if taken for non-arthritic reasons (≤ 325 mg/day).
  10. If female participant, has met either criterion "a" or "b" below:

    1. Is of non-childbearing potential (amenorrheic for at least 2 years, or had a hysterectomy and/or bilateral oophorectomy at least 8 weeks prior to screening);

      • All other female patients (including those with tubal ligation) will be considered of childbearing potential.

    2. Is of childbearing potential and willing to use the acceptable methods of contraception and abide by the timelines of each method.
  11. If male participant, must be willing to use the acceptable methods of contraception and abide by the timelines.

Exclusion Criteria:

  1. Diagnosis of any other active or uncontrolled inflammatory or non-inflammatory articular disease that may interfere with disease activity assessments;
  2. Previously treated with IV immunoglobulins within 6 months of first dose of Study Drug;
  3. History of:

    1. Significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological or dermatological disease;
    2. Significant cardiac disease, myocardial infarction within 6 months of screening, unstable angina, congestive heart failure (New York Heart Association [NYHA] Class III-IV), known arrhythmias of ventricular etiology, unexplained syncope or syncope/seizures related to arrhythmia;
    3. Serious infection (defined as requiring parenteral antibiotics or hospitalization) within 6 months of first dose of Study Drug;
    4. Active tuberculosis or history of tuberculosis without documented curative treatment and/or positive tuberculin reaction to PPD (Purified Protein Derivative) without known vaccination with the Bacillus Calmette - Guerin vaccine (BCG). Prior history of BCG with positive reaction to PPD will require follow-up negative chest X-ray;
    5. Significant trauma or major surgery within 8 weeks of first dose of Study Drug;
    6. Alcohol abuse with less than 12 months of sobriety, or any drug abuse within 3 years of first dose of Study Drug;
    7. Cancer unless in complete remission for ≥ 5 years, excluding patients with adequately treated or excised nonmetastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ;
    8. Participation in another clinical trial within 4 weeks of Screening.
  4. Presenting with any of the following:

    1. Severe psychological illness or any condition which will interfere with the patient's ability to understand and/or comply with the requirements of the study;
    2. Any condition possibly affecting oral drug absorption (e.g., gastrectomy, malabsorption, Crohn's disease or clinically significant diabetic gastroenteropathy);
    3. A documented body temperature ≥ 37.5˚C (99.5 ˚F) at Screening and Baseline (e.g., pre-dose on Day 1);
    4. An infection with human immunodeficiency virus (HIV) or hepatitis B or C;
    5. Any clinically significant active infection including herpes lesions;
    6. A confirmed mean of the screening triplicate QTc interval > 450 ms by Fridericia's formula as calculated by the site.
  5. Evidence of organ dysfunction or hematopoietic disorder based on any of the following assessments at Screening:

    1. Hgb ≤ 10 g/dL or Hct ≤ 32%;
    2. Absolute WBC count ≤ 3.0 × 109/L (3000/mm3);
    3. Neutrophil count ≤ 1.2 × 109/L (1200/mm3);
    4. Platelet count ≤ 100 × 109/L (100,000/mm3);
    5. AST (aspartate aminotransaminase) or ALT (alanine aminotransaminase) ≥ 1.2 × upper limit of normal (ULN);
    6. Total bilirubin ≥ 1.5 × ULN;
    7. Alkaline phosphatase ≥ 1.5 × ULN;
    8. Albumin ≤ 3.5 g/dL (35 g/L);
    9. Serum creatinine ≥ 1.2 × ULN;
    10. Thyroid-stimulating hormone (TSH) ≥ 1.2 × ULN unless clinically euthyroid and receiving a stable dose of thyroxine.
  6. Patients requiring prohibited concomitant medications including moderate or strong CYP3A inhibitors, CYP3A inducers and Biologic Response Modifiers (BRMs) while on study;
  7. Pregnant or breastfeeding patients.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00811499

Locations
United States, Nebraska
Westroads Medical Group Recruiting
Omaha, Nebraska, United States, 68114
Contact: Tonya Neil     402-934-1666     research@wmgmed.com    
Principal Investigator: William Palmer, MD            
United States, Washington
Arthritis Northwest Recruiting
Spokane, Washington, United States, 99204
Contact: Gretchen Mladjan     509-838-6500     gmladjan@arthritisnw.com    
Principal Investigator: Gary Craig, MD            
Sponsors and Collaborators
Array BioPharma
  More Information

Responsible Party: Array BioPharma ( Cynthia Schechter )
Study ID Numbers: ARRAY-797-201
Study First Received: December 17, 2008
Last Updated: December 30, 2008
ClinicalTrials.gov Identifier: NCT00811499  
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Spinal Diseases
Musculoskeletal Diseases
Spondylarthropathy
Arthritis
Joint Diseases
Spondylitis, Ankylosing
Spondylarthritis
Bone Diseases
Spondylitis
Ankylosis
Spondylarthropathies

Additional relevant MeSH terms:
Infection
Bone Diseases, Infectious

ClinicalTrials.gov processed this record on January 14, 2009