Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-3)

Rheumatoid Arthritis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00665626
• Other study ID #: C-935788-011
• Status: Completed
• Phase: Phase 2
• First received: April 22, 2008
• Last updated: June 17, 2009
• Start date: May 2008
• Est. completion date: June 2009

Study information

• Verified date: June 2009
• Source: Rigel Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardBelgium: Federal Agency for Medicinal Products and Health ProductsBelgium: Institutional Review BoardBrazil: Ethics Committee (Ethic Committee of each institution)Brazil: Ministry of Health (Conselho Nacional de Saude, CNS)Brazil: National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa, CONEP)Brazil: National Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria, ANVISA)Colombia: Ministry of Health (INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos)Colombia: Ethics Committee (Ethic Committee of each institution)France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Institutional Ethical CommitteeGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthPeru: Ethics Committee (19 registered IECs, the one used for this study is Comite de Etica de la Universidad de San Martin de Porres, CEUSMP).Peru: General Directorate of Pharmaceuticals, Devices, and Drugs (Dirección general de medicamentos, insumos y drogas, DIGEMID)Peru: Ministry of Health (Instituto Nacional de Salud, INS)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. completion date: June 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Fostamatinib disodium (R935788)
R935788 100 mg tablet, orally, twice-a-day

Locations

Country	Name	City	State
Belgium	ZNA Middelheim	Antwepen
Belgium	UZ Gent	Gent
Belgium	CHU Liege	Liege
Colombia	Centro de Reumatologiay Ortopedia	Barranquilla	Atlantico
Colombia	Reumatologos del Caribe	Barranquilla	Atlantico
Colombia	CIREEM	Bogota	Cundinamarca
Colombia	Dr. Renato Guzman	Bogota	Cundinamarca
Colombia	Riesgo de Fractura S.A.	Bogota	Cundinamarca
Colombia	SERVIMED	Bucaramanga	Santander
Colombia	Reumalab S.A.	Medellin	Antioquia
France	Hopital Pellegrin	Bordeaux Cedex
France	CHUG Hopital Sud	Echirolles
France	CHR Hopital Roger Salengro	Lille
France	Hopital Lapeyronie	Montpellier
France	Nouvel Hopital Civil	Strasbourg
Germany	Charite-Univeristaets medizin Berlin	Berlin
Germany	ClinPharm International GmbH Berlin	Berlin
Germany	ClinPharm International GmbH Bochum	Bochum
Germany	ClinPharm International GmbH Chemnitz	Chemnitz
Germany	ClinPharm International GmbH Dresden	Dresden
Germany	Universitatsklinikum Erlangen	Erlangen
Germany	ClinPharm International GmbH Frankfurt	Frankfurt
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Klinikum Eilbek	Hamburg
Germany	ClinPharm International GmbH Leipzig	Leipzig
Germany	Rheumazentrum am Universitatsklinikum Leipzig	Leipzig
Germany	ClinPharm International GmbH Potsdam	Potsdam
Germany	Ev. Fachkrankenhaus Ratingen	Ratingen
Germany	Universitatsklinikum Wurzburg	Wurzburg
Italy	Servizio di Reumatologia Policlinico di Modena	Modena
Italy	Reumatologia Azienda Ospedaliera Universitaria	Siena
Italy	Azienda Ospedaliera Santa Maria della Miseri	Udine
Peru	Hospital Nacional Alberto Sabogal Sologuren E	Callao
Peru	Rheumatology Clinica San Felipe	Jesus Maria	Lima
Peru	Clinica Ricardo Palma	Lima
Peru	Instituto de Ginecologia y Reproduccion	Lima
United States	Arthritis Clinic of Northern Virginia, P.C.	Arlington	Virginia
United States	Austin Rheumatology & Research	Austin	Texas
United States	Arthritis & Rheumatic Disease Specialties	Aventura	California
United States	RASF-Clinical Research Center	Boca Raton	Florida
United States	Intermountain Orthopedics	Boise	Idaho
United States	Rheumatology Associates	Charleston	South Carolina
United States	Rheumatology Associates, SC	Chicago	Illinois
United States	Arthritis Associates of Colorado Springs	Colorado Springs	Colorado
United States	The Osteoporosis & Clinical Trials Center	Cumberland	Maryland
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Center for Arthritis & Osteoperosis	Elizabethtown	Kentucky
United States	Rheumatology Associates	Erie	Pennsylvania
United States	Florida Medical Research Institute	Gainsville	Florida
United States	Holzer Clinic	Gallipolis	Ohio
United States	The Osteoporosis & Clinical Trials Center	Hagerstown	Maryland
United States	Arthritis & Osteoporosis Center, PC	Hamden	Connecticut
United States	Accurate Clinical Research	Houston	Texas
United States	Houston Institute for Clinical Research	Houston	Texas
United States	Rheumatic Disease Clinical Research	Houston	Texas
United States	North Shore Long Island Jewich Health System	Lake Success	New York
United States	Fiechtner Research, Inc.	Lansing	Michigan
United States	Clinical Research Division	Mayfield Village	Ohio
United States	Paddock Park Clinical Research	Ocala	Florida
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Westroads Medical Group	Omaha	Nebraska
United States	Jeffrey Poiley	Orlando	Florida
United States	Desert Medical Advances	Palm Desert	California
United States	Stanford University School of Medicine	Palo Alto	California
United States	North Carolina Arthritis & Allergy Care Cente	Raleigh	North Carolina
United States	Andrew Porges, MD PC	Roslyn	New York
United States	University of California at Davis Medical Center	Sacramento	California
United States	San Diego Arthritis & Medical Clinic	San Diego	California
United States	Lovelace Scientific Resources	Sarasota	Florida
United States	Rheumatology Associates of Long Island	Smithtown	New York
United States	Memorial Medical Group Clinical Research Inst	South Bend	Indiana
United States	Arthritis Northwest, PLLC	Spokane	Washington
United States	Tampa Medical Group	Tampa	Florida
United States	Department of Rheumatology	Washington	District of Columbia
United States	Clinical Research Center of Reading, LLP	West Reading	Pennsylvania
United States	Rheumatic Disease Associates	Willow Grove	Pennsylvania
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Rigel Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  Colombia,  France,  Germany,  Italy,  Peru, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective of this study is to assess the efficacy of R788 100 mg PO bid compared with placebo, as determined by ACR20 responder rates at Month 3.		Month 3	No
Secondary	To assess the response rate of R788 100 mg PO bid as determined by ACR50, ACR70, ACRn, DAS28-CRP, and DAS28-ESR at Month 3		Month 3	No
Secondary	To assess the rapidity of onset of clinical effect of R788 100 mg PO bid compared with placebo as determined by ACR20 response rates at Weeks 1 and 2		Week 1 and Week 2	No
Secondary	To assess the radiologic response of R788 100 mg PO bid compared with placebo as determined by Magnetic Resonance Imaging (MRI) using the modified RAMRIS scoring system of hands and wrists at baseline and Month 3		Month 3	No
Secondary	To assess and compare the safety profiles of R788 100 mg PO bid dose with placebo for effects on liver function tests, clinically significant reduction in peripheral neutrophil counts, G-I side effects and other adverse effects as they may appear.		Study	Yes