A PHASE 2, 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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-007510-30-HU
• Date of registration: 29/12/2008
• Prospective Registration: Yes
• Primary sponsor: Array BioPharma Inc.
• Public title: A PHASE 2, 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
• Scientific title: A PHASE 2, 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
• Date of first enrolment: 09/02/2009
• Target sample size: 126
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007510-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: multi-center If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Hungary, Poland

Key inclusion & exclusion 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 must NOT have failed due to lack of efficacy, and has completed the following washouts (calculated from first dose of Study Drug):
a. Within 4 weeks of first dose of Study Drug: etanercept (Enbrel®), anakinra (Kineret®);
b. Within 8 weeks of first dose of Study Drug: infliximab (Remicade®), adalimumab (Humira®);
8. Has completed a 4-week washout period (calculated from first dose of Study Drug), if treated with any of the following therapies:
a. Any experimental therapy (within or outside a clinical trial setting);
b. Intramuscular or intravenous corticosteroids;
c. 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:
a. Non-investigational NSAIDs and/or COX-2 inhibitors;
b. DMARDs—methotrexate (= 25 mg/week), sulfasalazine (= 3 gm/day), leflunomide (= 20 mg/day);
c. Hydroxychloroquine (= 400 mg/day);
d. Low-dose oral corticosteroids (= 10 mg prednisone or equivalent per day);
e. Opioid analgesics (= 30 mg oral morphine or equivalent per day);
f. Acetaminophen (paracetamol) = 4000 mg/day (4 g/day);
g. Aspirin if taken for non-arthritic reasons (= 325 mg/day).
10. If female participant, has met either criterion “a” or “b” below:
a. 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.
b. 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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:
a. Significant renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological or dermatological disease;
b. 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;
c. Serious infection (defined as requiring parenteral antibiotics or hospitalization) within 6 months of first dose of Study Drug;
d. 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;
e. Significant trauma or major surgery within 8 weeks of first dose of Study Drug;
f. Alcohol abuse with less than 12 months of sobriety, or any drug abuse within 3 years of first dose of Study Drug;
g. Cancer unless in complete curative 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;
h. Participation in another clinical trial within 4 weeks of Screening.
4. Presenting with any of the following:
a. 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;
b. Any condition possibly affecting oral drug absorption (e.g., gastrectomy, malabsorption, Crohn’s disease or clinically significant diabetic gastroenteropathy);
c. A documented body temperature = 37.5°C (99.5 °F) at Screening and Baseline (e.g., pre-dose on Day 1);
d. An infection with human immunodeficiency virus (HIV) or hepatitis B or C;
e. Any clinically significant active infection including herpes lesions;
f. A confirmed mean of the screening triplicate QTc interval > 450 ms by Fridericia’s formula as calculated by the site.
g. Total fusion of the spine
5. Evidence of organ dysfunction or hematopoietic disorder based on any of the following assessments at Screening:
a. Hgb = 10 g/dL or Hct = 32%;
b. Absolute WBC count = 3.0 × 109/L (3000/mm3);
c. Neutrophil count = 1.2 × 109/L (1200/mm3);
d. Platelet count = 100 × 109/L (100,000/mm3);
e. AST (aspartate aminotransaminase) or ALT (alanine aminotransaminase) = 1.2 × upper limit of normal (ULN);
f. Total bilirubin = 1.5 × ULN;
g. Alkaline phosphatase = 1.5 × ULN;
h. Albumin = 3.5 g/dL (35 g/L);
i. Serum creatinine = 1.2 × ULN;
j. Thyroid-stimulating hormone (TSH) = 1.2 × ULN unless clinically euthyroid and receiving a stable dose of thryroxine.
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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ANKYLOSING SPONDYLITIS
MedDRA version: 9.1 Level: LLT Classification code 10002556 Term: Ankylosing spondylitis

Intervention(s)

Product Name: ARRY-371797
Pharmaceutical Form: Capsule, hard
CAS Number: 765914-60-1
Current Sponsor code: ARRY-371797
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 100-200
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: •To compare the efficacy of ARRY-371797 (200 mg q12h and 400 mg q24h) versus placebo in patients with active ankylosing spondylitis (AS).
•To evaluate the safety of ARRY-371797 in patients with active AS.

Primary end point(s): The primary endpoint will be ASAS 20 response at Week 12

Secondary Objective: •To evaluate the exposure of ARRY-371797 and a metabolite (AR00333953) in plasma after the administration of ARRY-371797.
•To evaluate the effect of two dose regimens of ARRY-371797 versus placebo on measures of disease activity.
•To evaluate the pharmacodynamic effects of two dose regimens of ARRY-371797 on circulating levels of exploratory markers of disease activity

Secondary ID(s)

ARRAY 797-201