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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00665626
• Date of registration: 22/04/2008
• Prospective Registration: Yes
• Primary sponsor: Rigel Pharmaceuticals
• Public title: Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-3) Taski-3
• Scientific 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
• Date of first enrolment: May 2008
• Target sample size: 219
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00665626
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

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

Contacts

• Name: Daniel B Magilavy, MD
• Affiliation: Rigel Pharmaceuticals

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Fostamatinib disodium (R935788)

Drug: Placebo

Primary Outcome(s)

American College of Rheumatology 20 (ACR20) Response at 3 Months [Time Frame: 3 months]

Secondary Outcome(s)

Alanine Aminotransferase (ALT) >1.5-2x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

American College of Rheumatology Index of Improvement (ACRn) at 3 Months [Time Frame: 3 months]

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 Months [Time Frame: 3 months]

Alanine Aminotransferase (ALT) >2-3x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Alanine Aminotransferase (ALT) >3-5x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Alkaline Phosphatase >1.5x Upper Limit of Normal (ULN) and >1.5x Baseline [Time Frame: Any time between baseline and 3 months]

Absolute Neutrophil Count (ANC) <1500/mm3 [Time Frame: Any time between baseline and 3 months]

American College of Rheumatology 20 (ACR20) Response at Week 1 [Time Frame: 1 week]

American College of Rheumatology 70 (ACR70) Response at 3 Months [Time Frame: 3 months]

Aspartate Aminotransferase (AST) >1.5x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

American College of Rheumatology 20 (ACR20) Response at Week 2 [Time Frame: 2 weeks]

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 Months [Time Frame: 3 months]

Aspartate Aminotransferase (AST) >3x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 Months [Time Frame: 3 months]

Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Synovitis Score at 3 Months [Time Frame: Baseline to 3 months]

American College of Rheumatology 50 (ACR50) Response at 3 Months [Time Frame: 3 months]

Aspartate Aminotransferase (AST) >1.5-2x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Aspartate Aminotransferase (AST) >5-10x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Bilirubin >1.5x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 Months [Time Frame: 3 months]

Alanine Aminotransferase (ALT) >1.5x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Alanine Aminotransferase (ALT) >10x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Alanine Aminotransferase (ALT) >3x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Alanine Aminotransferase (ALT) >5-10x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Aspartate Aminotransferase (AST) >3-5x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Erosion Score at 3 Months [Time Frame: Baseline to 3 months]

Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Osteitis Score at 3 Months [Time Frame: Baseline to 3 months]

Aspartate Aminotransferase (AST) >10x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Aspartate Aminotransferase (AST) >2-3x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Bilirubin >2x Upper Limit of Normal (ULN) [Time Frame: Any time between baseline and 3 months]

Secondary ID(s)

C-935788-011

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/07/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00665626