Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Methotrexate But Not Responding.

NCT01197521 | Completed Phase 3 Results DMC

• 2 other identifiers: D4300C000012010-020743-12
• Study Type: interventional
• Target: 923
• Locations: 17 countries
• Sites: 127

Brief Summary

The purpose of the study is to evaluate the effectiveness of two dosing regimens of fostamatinib compared to placebo, in patients with rheumatoid arthritis (RA) who are taking methotrexate but not responding. The study will last for 1 year.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Proportion of Patients With ACR20 at Week 24, Comparison Between Fostamatinib and Placebo.

  ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID=twice daily, CRP=C-reactive protein, DMARD=disease-modifying anti-rheumatic drug, PO=orally, QD=once a day.

  24 weeks

• Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo.

  mTSS: modified total Sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 448. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values have had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result have been excluded from the analysis. ANCOVA=analysis of covariance, BID=twice daily, DMARD=disease-modifying anti-rheumatic drug, IP=investigational product, PO=orally, QD=once a day.

  Baseline and 24 weeks

Secondary Outcomes (10)

• ACR20 - Proportion of Patients Achieving ACR20, Comparison Between Fostamatinib and Placebo at Week 1

  1 week

• Proportion of Patients Achieving ACR50 up to Week 24

  24 weeks

• Proportion of Patients Achieving ACR70 up to Week 24

  24 weeks

• ACRn - Comparison Between Fostamatinib and Placebo at Week 24

  24 weeks

• Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12

  12 weeks

Study Arms (3)

Dosing Regimen A

EXPERIMENTAL

Oral Treatment

Drug: fostamatinib

Dosing Regimen B

EXPERIMENTAL

Oral Treatment

Drug: fostamatinib

Dosing Regimen C

PLACEBO COMPARATOR

Oral Treatment

Drug: placebo, fostamatinib

Interventions

fostamatinib DRUG

fostamatinib 100 mg twice daily

Dosing Regimen A

placebo, fostamatinib DRUG

Placebo for 24 weeks followed by fostamatinib 100 mg twice daily

Dosing Regimen C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Active rheumatoid arthritis (RA) diagnosed after the age of 16
• Currently taking methotrexate
• or more swollen joints and 6 or more tender/painful joints (from 28 joint count) and either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or C-Reactive Protein (CRP) blood result of 10mg/L or more
• At least one of the following: documented history of positive rheumatoid factor (blood test), current presence of rheumatoid factor (blood test), radiographic erosion within 12 months prior to study enrolment, presence of serum anti-cyclic citrullinated peptide antibodies (blood test)

You may not qualify if:

• Females who are pregnant or breast feeding
• Poorly controlled hypertension
• Liver disease or significant liver function test abnormalities
• Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders
• Recent or significant cardiovascular disease
• Significant active or recent infection including tuberculosis
• Previous failure to respond to a TNF alpha antagonist, anakinra or previous treatment with other biological agent
• Severe renal impairment
• Neutropenia

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (127)

Research Site

Anniston, Alabama, United States

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Huntsville, Alabama, United States

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Tuscaloosa, Alabama, United States

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Tucson, Arizona, United States

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Huntington Beach, California, United States

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Long Beach, California, United States

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Santa Maria, California, United States

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Santa Monica, California, United States

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Colorado Springs, Colorado, United States

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Bridgeport, Connecticut, United States

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Lewes, Delaware, United States

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Daytona Beach, Florida, United States

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Ocala, Florida, United States

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Atlanta, Georgia, United States

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Marietta, Georgia, United States

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Idaho Falls, Idaho, United States

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Springfield, Illinois, United States

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Wichita, Kansas, United States

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Bowling Green, Kentucky, United States

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Flowood, Mississippi, United States

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Florissant, Missouri, United States

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Richmond Heights, Missouri, United States

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St Louis, Missouri, United States

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Kalispell, Montana, United States

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Albuquerque, New Mexico, United States

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Albany, New York, United States

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Brooklyn, New York, United States

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Olean, New York, United States

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Asheville, North Carolina, United States

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Greensboro, North Carolina, United States

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Perrysburg, Ohio, United States

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Lake Oswego, Oregon, United States

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Erie, Pennsylvania, United States

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Waxford, Pennsylvania, United States

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Charleston, South Carolina, United States

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Hixson, Tennessee, United States

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Memphis, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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Mesquite, Texas, United States

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San Antonio, Texas, United States

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Reading, Berkshire, Argentina

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Buenos Aires, Buenos Aires F.D., Argentina

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Ciudad Autonoma Bs As, CBA, Argentina

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Córdoba, CRD, Argentina

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San Juan, San Juan Province, Argentina

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Rosario, Santa Fe Province, Argentina

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San Miguel de Tucumán, TUC, Argentina

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Caba, Argentina

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Quilmes, Argentina

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Camperdown, New South Wales, Australia

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Cairns, Queensland, Australia

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Southport, Queensland, Australia

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Brussels, Belgium

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Yvoir, Belgium

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Vitória, Espírito Santo, Brazil

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Curitiba, Paraná, Brazil

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Recife, Pernambuco, Brazil

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São Paulo, São Paulo, Brazil

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Rio de Janeiro, Brazil

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Plovdiv, Bulgaria

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Sevlievo, Bulgaria

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Sofia, Bulgaria

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Veliko Tarnovo, Bulgaria

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Osorno, Los Lagos Region, Chile

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Santiago, Chile

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Pärnu, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Orléans, France

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Paris, France

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Balatonfüred, Hungary

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Békéscsaba, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Makó, Hungary

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Sopron, Hungary

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Szentes, Hungary

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Zalaegerszeg-pozva, Hungary

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Secunderabad, Andhra Pradesh, India

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Visakhapatnam, Andhra Pradesh, India

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Ahmedabad, Gujarat, India

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Bangalore, Karnataka, India

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Mangalore, Karnataka, India

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Udupi, Karnataka, India

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Nagpur, Maharshtra, India

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Lucknow, Uttar Pradesh, India

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Hyderabad, India

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Kolkata, India

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Chihuahua City, Chihuahua, Mexico

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Saltillo, Coahuila, Mexico

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Guadalajara, Jalisco, Mexico

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Mexico City, Mexico City, Mexico

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San Luis Potosi, Mexico, Mexico

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Monterrey, Nuevo León, Mexico

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Obrergon, Sonora, Mexico

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Mexicali, Mexico

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Arequipa, Arequipa, Peru

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Lima, Lima Province, Peru

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Pueblo Libre, Lima region, Peru

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Bytom, Poland

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Chełm Śląski, Poland

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Grodzisk Mazowiecki, Poland

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Katowice, Poland

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Krakow, Poland

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Warsaw, Poland

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Wroclaw, Poland

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Żyrardów, Poland

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Bratislava, Slovakia, Slovakia

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Žilina, Slovakia, Slovakia

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Poprad, Slovakia

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Rimavská Sobota, Slovakia

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Donetsk, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Kiev, Ukraine

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Kyiv, Ukraine

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Lviv, Ukraine

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Odesa, Ukraine

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Vinnytsia, Ukraine

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Zaporyzhzhya, Ukraine

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Warrington, Cheshire, United Kingdom

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Christchurch, United Kingdom

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Ipswich, United Kingdom

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London, United Kingdom

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Metropolitan Borough of Wirral, United Kingdom

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Westcliff-on-the Sea, United Kingdom

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Related Publications (1)

• Kjelgaard-Petersen CF, Platt A, Braddock M, Jenkins MA, Musa K, Graham E, Gantzel T, Slynn G, Weinblatt ME, Karsdal MA, Thudium CS, Bay-Jensen AC. Translational Biomarkers and Ex Vivo Models of Joint Tissues as a Tool for Drug Development in Rheumatoid Arthritis. Arthritis Rheumatol. 2018 Sep;70(9):1419-1428. doi: 10.1002/art.40527. Epub 2018 Jul 24.

  PMID: 29669391 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

fostamatinib

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Dave Goldstraw
• Organization: AstraZeneca

dave.goldstraw@astrazeneca.com

+44 (0)1625 512415

Study Officials

• Neil MacKillop, MD PhD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2010
• First Posted: September 9, 2010
• Study Start: September 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: April 7, 2014
• Results First Posted: April 7, 2014

Record last verified: 2014-02

Locations

US (41); AR (9); ME (8); PE (3); BE (2); CL (2); HU (8); AU (3); PL (8); SL (4); GB (6); BU (4); ES (3); FR (2); IN (10); BR (5); UA (9)