Clinical trial NCT00665626: Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-3)
Official title: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Patients With Rheumatoid Arthritis Who Have Failed at Least One Biologic
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Rigel Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-04-24
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) Inhibitor, R935788 (R788) at a dose of 100 mg, tablet, orally, twice-a-day is effective in the treatment of Rheumatoid Arthritis in patients who have 'failed' a biologic therapy.


Eligibility criteria: Inclusion Criteria:

* Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
* Males and females, 18 years of age or older, with active RA for at least 12 months prior to Day 1 dosing
* Are currently receiving or previously had received a biologic therapy with an inhibitor of TNF, rituximab, abatacept, or anakinra at an approved labeled dose for ≥3 months prior to Day 1 dosing and are designated as biologic therapy failures for lack of efficacy, safety, or tolerability.
* Patients may receive stable doses of methotrexate (MTX), azathioprine (not in combination with MTX), leflunomide (not in combination with MTX), sulfasalazine, chloroquine, hydroxychloroquine, gold, NSAIDs (including COX2 inhibitors), minocycline, or doxycycline. The dose must have been stable for at least 30 days prior to Day 1 dosing and must not be changed during the washout, screening and treatment periods, unless dictated by tolerability requirements. Patients who are taking MTX must have been receiving weekly MTX doses (7.5-25 mg/week) for a minimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in route, for the previous 6 weeks prior to Day 1 dosing. Patients who are receiving MTX must also be receiving folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing.
* Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
* The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
* In the Investigator's opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.

Exclusion Criteria:

* The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:

  1. uncontrolled or poorly controlled hypertension;
  2. other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);
  3. recent serious surgery or infectious disease;
  4. recent history ( of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma;
  5. Hepatitis B;
  6. Hepatitis C;
  7. interstitial pneumonitis or active pulmonary infection on chest x-ray
  8. Tuberculosis (TB)
  9. known laboratory abnormalities
* The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.
* The patient has been treated previously treated with R788 under a different protocol.
* The patient has a pacemaker, aneurysm clip or other contraindication to MRI.

Primary outcomes:
measure: American College of Rheumatology 20 (ACR20) Response at 3 Months
timeFrame: 3 months
Secondary outcomes:
measure: American College of Rheumatology 50 (ACR50) Response at 3 Months
timeFrame: 3 months
measure: American College of Rheumatology 70 (ACR70) Response at 3 Months
timeFrame: 3 months
measure: American College of Rheumatology Index of Improvement (ACRn) at 3 Months
timeFrame: 3 months
measure: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 Months
timeFrame: 3 months
measure: Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 Months
timeFrame: 3 months
measure: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 Months
timeFrame: 3 months
measure: Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 Months
timeFrame: 3 months
measure: American College of Rheumatology 20 (ACR20) Response at Week 1
timeFrame: 1 week
measure: American College of Rheumatology 20 (ACR20) Response at Week 2
timeFrame: 2 weeks
measure: Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Erosion Score at 3 Months
timeFrame: Baseline to 3 months
measure: Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Osteitis Score at 3 Months
timeFrame: Baseline to 3 months
measure: Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Synovitis Score at 3 Months
timeFrame: Baseline to 3 months
measure: Alanine Aminotransferase (ALT) >1.5x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alanine Aminotransferase (ALT) >1.5-2x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alanine Aminotransferase (ALT) >2-3x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alanine Aminotransferase (ALT) >3x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alanine Aminotransferase (ALT) >3-5x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alanine Aminotransferase (ALT) >5-10x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alanine Aminotransferase (ALT) >10x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >1.5x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >1.5-2x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >2-3x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >3x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >3-5x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >5-10x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Aspartate Aminotransferase (AST) >10x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Alkaline Phosphatase >1.5x Upper Limit of Normal (ULN) and >1.5x Baseline
timeFrame: Any time between baseline and 3 months
measure: Bilirubin >1.5x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Bilirubin >2x Upper Limit of Normal (ULN)
timeFrame: Any time between baseline and 3 months
measure: Absolute Neutrophil Count (ANC) <1500/mm3
timeFrame: Any time between baseline and 3 months
Other outcomes:
Locations:
city: Aventura
country: United States
facility: Arthritis & Rheumatic Disease Specialties
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: San Diego
country: United States
facility: San Diego Arthritis & Medical Clinic
state: California
city: Washington
country: United States
facility: Department of Rheumatology
state: District of Columbia
city: Boca Raton
country: United States
facility: RASF-Clinical Research Center
state: Florida
city: Gainsville
country: United States
facility: Florida Medical Research Institute
state: Florida
city: Ocala
country: United States
facility: Paddock Park Clinical Research
state: Florida
city: Sarasota
country: United States
facility: Lovelace Scientific Resources
state: Florida
city: Boise
country: United States
facility: Intermountain Orthopedics
state: Idaho
city: Chicago
country: United States
facility: Rheumatology Associates, SC
state: Illinois
city: South Bend
country: United States
facility: Memorial Medical Group Clinical Research Inst
state: Indiana
city: Elizabethtown
country: United States
facility: Center for Arthritis & Osteoperosis
state: Kentucky
city: Cumberland
country: United States
facility: The Osteoporosis & Clinical Trials Center
state: Maryland
city: Hagerstown
country: United States
facility: The Osteoporosis & Clinical Trials Center
state: Maryland
city: Lansing
country: United States
facility: Fiechtner Research, Inc.
state: Michigan
city: Omaha
country: United States
facility: Westroads Medical Group
state: Nebraska
city: Lake Success
country: United States
facility: North Shore Long Island Jewich Health System
state: New York
city: Roslyn
country: United States
facility: Andrew Porges, MD PC
state: New York
city: Smithtown
country: United States
facility: Rheumatology Associates of Long Island
state: New York
city: Mayfield Village
country: United States
facility: Clinical Research Division
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Erie
country: United States
facility: Rheumatology Associates
state: Pennsylvania
city: West Reading
country: United States
facility: Clinical Research Center of Reading, LLP
state: Pennsylvania
city: Willow Grove
country: United States
facility: Rheumatic Disease Associates
state: Pennsylvania
city: Austin
country: United States
facility: Austin Rheumatology & Research
state: Texas
city: Houston
country: United States
facility: Houston Institute for Clinical Research
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest, PLLC
state: Washington
city: Antwepen
country: Belgium
facility: ZNA Middelheim
city: Gent
country: Belgium
facility: UZ Gent
city: Liege
country: Belgium
facility: CHU Liege
city: Medellin
country: Colombia
facility: Reumalab S.A.
state: Antioquia
city: Barranquilla
country: Colombia
facility: Reumatologos del Caribe
state: Atlantico
city: Bogota
country: Colombia
facility: CIREEM
state: Cundinamarca
city: Bogota
country: Colombia
facility: Dr. Renato Guzman
state: Cundinamarca
city: Bogota
country: Colombia
facility: Riesgo de Fractura S.A.
state: Cundinamarca
city: Bordeaux Cedex
country: France
facility: Hopital Pellegrin
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe Universitaet
city: Hamburg
country: Germany
facility: Klinikum Eilbek
city: Leipzig
country: Germany
facility: ClinPharm International GmbH Leipzig
city: Leipzig
country: Germany
facility: Rheumazentrum am Universitatsklinikum Leipzig
city: Wurzburg
country: Germany
facility: Universitatsklinikum Wurzburg
city: Siena
country: Italy
facility: Reumatologia Azienda Ospedaliera Universitaria
city: Udine
country: Italy
facility: Azienda Ospedaliera Santa Maria della Miseri
city: Lima
country: Peru
facility: Instituto de Ginecologia y Reproduccion
Study officials:
affiliation: Rigel Pharmaceuticals
name: Daniel B Magilavy, MD
role: STUDY_DIRECTOR
References: