Treatment of Arthritis With Syk Kinase Inhibition (TASKI-1)

Rheumatoid Arthritis Clinical Trial

Official title:

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose, Dose Ranging Study to Evaluate Up to Three Doses of R935788 in Rheumatoid Arthritis Patients Failing to Respond to Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00326339
• Other study ID #: C-935788-006
• Status: Completed
• Phase: Phase 2
• First received: May 12, 2006
• Last updated: April 16, 2009
• Start date: August 2006
• Est. completion date: December 2007

Study information

• Verified date: March 2008
• Source: Rigel Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationMexico: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This is a Phase II, multicenter, randomized, double-blind, placebo-controlled, ascending dose, dose ranging study to evaluate up to three doses of R935788 (50 mg bid, 100 mg bid and 150 mg bid). Approximately 180 patients who have had rheumatoid arthritis for a minimum of 12 months and who have been receiving a weekly methotrexate (MTX) dose for a minimum of 6 months will be enrolled into the study.

Description:

The primary objective of this study is to assess the preliminary efficacy of up to three different dosage regimens of R788 as determined by ACR 20 responder rates at 12 weeks The secondary objectives of this study are to assess the safety of up to three different dosage regimens of R788 as determined by ACR 20 responder rates at 12 weeks, and to assess the general clinical and laboratory safety evaluations throughout the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: December 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients must give written informed consent by signing an IRB-approved Informed Consent Form (ICF) prior to admission to this study.

2. Males and females, 18 to 75 years of age, with active RA for at least 12 months (functional class I-III, e.g., not bed or wheelchair-bound) who have been receiving weekly doses of methotrexate (10-25 mg/week) for a minimum of 180 days, and who have been receiving a stable MTX dose of at least 15 mg without any change in route or change in folic acid supplementation for at least 30 days.

Active RA is defined as the presence of (a)6 swollen joints (28 joint count); AND (b)6 tender joints (28 joint count); AND (c) CRP level > ULN for the central reference laboratory.

Patient may receive up to 10 mg per day of oral prednisone or steroid equivalent, NSAID therapy, hydroxychloroquine, chloroquine, minocycline, sulfasalazine, and doxycycline. The dose(s) must have been stable for at least 30 days and must not be changed during the washout, screening and treatment periods, unless dictated by tolerability requirements.

3. Females of childbearing potential must be fully informed of the potential for methotrexate and R788 to adversely affect the fetus and must agree to use adequate (2 methods) contraception during the study. These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.

4. The patient is in otherwise good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period, including the absence of clinically significant findings, such as HIV, HBV or HCV, interstitial pneumonitis or active pulmonary infection, on chest X-ray taken within 6 months prior to screening and a negative TB skin test, or abnormal liver function defined as known ALT >1.2xULN within the past 90 days.

5. 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:

1. 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 (these will be included in an exclusion log).

2. The patient has a history of substance abuse, drug addiction or alcoholism.

3. The patient is unable to abstain from alcohol during the study.

4. The patient has a recent (past 5 years) history of, or treatment for, a malignancy other than basal skin cancer.

5. The patient has received any investigational medication within 30 days prior to admission to the study.

6. Any patient who has received any of the following treatments must abide by the indicated washout period:

1. oral or injectable gold, azathioprine, penicillamine, anakinra require a 30 day washout period prior to Day 1 dosing

2. cyclosporine, abatacept, etanercept, infliximab or adalimumab require a 60 day washout period prior to Day 1 dosing

3. leflunomide requires a 60 day washout period prior to screening, unless the patient has undergone cholestyramine washout at least 30 days prior to Day 1 dosing

4. cyclophosphamide requires a 180 day washout period prior to Day 1 dosing

5. Rituxan requires a 180 day washout period and normal CD19 count prior to Day 1 dosing

6. parenteral or intra-articular corticosteroids require a 30 day washout period prior to Day 1 dosing

7. Patients with the following laboratory abnormalities: ALT > 1.2X ULN, creatinine > ULN, a neutrophil count < 2,500/mm3 or lymphocyte count < 800/mm3, Hgb < 10 g/dL, platelet count < 125,000/mm3 are excluded.

8. Patients should not use CYP3A4 inhibitors from within 3 days of randomization until the end of study. R406 is metabolized by CYP3A4, and ketoconazole increases the R406 AUC of a dose of R788 by approximately 2 fold.

9. Patients should not use CYP3A4 inducers from within 3 days of randomization until the end of the study. Although glucocorticoids are inducers, a stable dose of no more than 10 mg/day is allowed.

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:
• R788
R788 50 mg, 100 mg, or 150 mg PO bid
• Placebo
Placebo PO bid

Locations

Country	Name	City	State
Mexico	Arke Estudios Clinicos, S.A. de C.V.	Ciudad Mexico	DF
Mexico	Clinica para el Diagnostico y Tratamiento de las Enfermedades Reumaticas, S.C.	Ciudad Mexico	DF
Mexico	Hospital General de Mexico	Ciudad Mexico	DF
Mexico	Hospital Regional "1° de Octubre", ISSSTE	Ciudad Mexico	DF
Mexico	Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"	Guadalajara	JA
Mexico	Hospital Civil de Guadalajara "Fray Antonio Alcalde"	Guadalajara	JA
Mexico	Hospital Aranda de la Parra	Leon	GT
Mexico	Centro Médico del Instituto de Seguridad Social del Estado de Mexico y Municipios (CMISSEMYM)	Metepec	MX
Mexico	Centro Médico DALINDE	Mexico	Distrito Federal
Mexico	Facultad de Medicina y Hospital Universitario "Dr. Jose E. Gonzalez" de la Universidad Autonoma de Nuevo Leon	Monterrey	NL
Mexico	Hospital Central "Dr. Ignacio Morones Prieto"	San Luis Potosi	SL
United States	Austin Rheumatology Research	Austin	Texas
United States	East Penn Rheumatology Associates	Bethlehem	Pennsylvania
United States	Michigan Arthritis Research Center	Brighton	Michigan
United States	Low Country Rheumatology	Charleston	South Carolina
United States	Center for Arth. & Rheum. Disease, PC	Chesapeake	Virginia
United States	Coeur d'Alene Arthritis Clinical Trials	Coeur d'Alene	Idaho
United States	Altoona Ctr. for Clinical Research	Duncansville	Pennsylvania
United States	Research Across America	El Paso	Texas
United States	Phase III Clinical Research	Fall River	Massachusetts
United States	Arthritis Clinic	Jackson	Tennessee
United States	Clinical Research Division	Mayfield Village	Ohio
United States	SCRI	Memphis	Tennessee
United States	DMI research	Ocala	Florida
United States	Renstar Medical Research	Ocala	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Westroad Medical Group	Omaha	Nebraska
United States	Arthritis & Osteoporosis Treatment Center	Orange Park	Florida
United States	Arthritis Associates Inc.	Orlando	Florida
United States	Arthritis Research of Florida	Palm Harbor	Florida
United States	Arthritis Research of Florida, Inc.	Palm Harbor	Florida
United States	NC Arthritis & Allergy Care Center	Raleigh	North Carolina
United States	Pacific Arthritis Center Medical Group	Santa Maria	California
United States	Lovelace Scientific Resources	Sarasota	Florida
United States	MMG Clinical Research	South Bend	Indiana
United States	The Center for Arthritis and Rheumatic Diseas	South Miami	Florida
United States	The Arthritis Center	Springfield	Illinois
United States	Clinical Research Center of Reading LLP	West Reading	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Rigel Pharmaceuticals

Countries where clinical trial is conducted

United States,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Primary Efficacy parameter is ACR20 response rate at 3 months post dosing.		12 weeks	No
Secondary	ACR 20/50 responses over time		12 weeks	No
Secondary	Disease Activity Score (DAS) at baseline and endpoint		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in Swollen Joint Count (28 joint count)		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in Tender Joint Count (28 joint count)		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in Physician global assessment of disease activity by visual analog scale (VAS)		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in Patient global assessment of disease activity by VAS		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in Patient assessment of pain by VAS		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in HAQ-DI		12 Weeks	No
Secondary	Mean changes (SDs) from baseline in CRP		12 Weeks	No
Secondary	The frequency and severity of Liver Function Test abnormalities, especially ALT and alkaline phosphatase		12 Weeks	Yes
Secondary	The frequency and severity of hematopoietic cytopenias, principally effects on neutrophil, erythrocyte, and lymphocyte counts		12 Weeks	Yes
Secondary	The frequency and severity of clinically significant adverse events, especially skin rash, postural dizziness, and alterations in blood pressure and other relevant clinical outcomes		12 Weeks	Yes