Randomised Double-Blind, Placebo-Controlled, Parallel Group Study in Patients With Active Rheumatoid Arthritis:Magnetic Resonance Imaging Sub-Study

NCT02092961 | Terminated Phase 2 Results DMC

• 1 other identifier: D4300C00004Sub
• Study Type: interventional
• Target: 198
• Locations: 11 countries
• Sites: 21

Brief Summary

This is a sub-study of the OSKIRA-4 study, (D4300C0004, NCT01264770) to explore alternative and more sensitive modalities for measuring the beneficial effects of syk inhibition with fostamatinib in patients with active RA. This MRI sub-study was reported later than the main study due to recruitment delays at specialist imaging sites and so is registered and presented entirely separately to the main study results. This study will investigate the impact of treatment on joint activity and damage by assessing synovitis, osteitis, bone erosions and joint space narrowing.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; OSKIRA; fostamatinib; CE-MRI; DCE-MRI

Outcome Measures

Primary Outcomes (1)

• OMERACT RAMRIS Synovitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)

  OMERACT RAMRIS synovitis score was based on 8 joints, scored from MRI images, and ranged from 0 to 24 with a smaller value indicating a better clinical condition. Median changes from baseline are shown at each visit (defined as post-baseline minus baseline) with negative values indicative of a better clinical condition. BID = twice daily, CI = confidence interval, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, MRI = magnetic resonance imaging, OMERACT = Outcome Measures in Rheumatoid Arthritis Clinical Trials, PO = orally, RAMRIS = Rheumatoid Arthritis Magnetic Resonance Image Scoring system, SC = subcutaneous.

  Baseline, 6 and 24 weeks

Other Outcomes (4)

• OMERACT RAMRIS Osteitis Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)

  Baseline, 6 and 24 weeks

• Joint Space Narrowing - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)

  Baseline, 6 and 24 weeks

• OMERACT RAMRIS Erosions Score - Comparison of Change From Baseline Between Fostamatinib and Placebo or Adalimumab (Van Elteren)

  Baseline, 6 and 24 weeks

Study Arms (3)

Dosing Group A

EXPERIMENTAL

Oral treatment and subcutaneous injection.

Drug: Fostamatinib; Drug: Placebo of Adalimumab

Dosing Group D

ACTIVE COMPARATOR

Oral treatment and subcutaneous injection.

Drug: Adalimumab; Drug: Placebo of Fostamatinib

Dosing Group E

PLACEBO COMPARATOR

Placebo bid for 6 weeks followed by switch to 100 mg fostamatinib bid for 24 weeks, plus placebo subcutaneous injection every 2 weeks.

Drug: Fostamatinib; Drug: Placebo of Fostamatinib; Drug: Placebo of Adalimumab

Interventions

Fostamatinib DRUG

Fostamatinib 100mg twice daily.

Dosing Group A; Dosing Group E

Adalimumab DRUG

Adalimumab 40 mg by subcutaneous injection every 2 weeks for 24 weeks.

Dosing Group D

Placebo of Fostamatinib DRUG

Placebo bid for 6 weeks.

Dosing Group D; Dosing Group E

Placebo of Adalimumab DRUG

Placebo injection once every two weeks.

Dosing Group A; Dosing Group E

Eligibility Criteria

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

You may qualify if:

• Male or female aged 18 and over
• Active rheumatoid arthritis (RA) diagnosed after the age of 16
• Diagnosis within 5 years prior to study visit 1 and inadequate response to treatment with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or
• diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or
• diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs
• or more swollen joints and 4 or more tender/painful joints (from 28 joint count)
• 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 2 of the following:
• documented history or current presence of positive rheumatoid factor (blood test),
• radiographic erosion within 12 months prior to study enrolment,
• presence of serum anti-cyclic citrullinated peptide antibodies (blood test)
• Presence of at least one swollen hand or wrist joint.
• Presence of synovitis on baseline MRI scan, defined as at least 1 joint with RAMRIS synovitis score of +1 or greater.

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
• Previously received treatment with a TNF alpha antagonist (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment with other biological agent including rituximab, abatacept and tocilizumab
• Use of any DMARDs within 6 weeks before first study visit
• Severe renal impairment
• Neutropenia
• Unable to undergo an MRI examination (e.g. presence of a pacemaker, defibrillator, or other implanted metallic device such as anterior interbody cages, aneurysm clip or pedicle screws)
• Known allergy to Gadolinium-based contrast agent,
• Tattoos \[in area of examination if contains metallic pigment\]
• Likely to require sedation for the procedure
• eGFR less than 55 mL/min

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (21)

Research Site

Glendale, Arizona, United States

Location

Research Site

Paradise Valley, Arizona, United States

Location

Research Site

Phoenix, Arizona, United States

Location

Research Site

Brooklyn, New York, United States

Location

Research Site

Jackson, Tennessee, United States

Location

Research Site

Austin, Texas, United States

Location

Research Site

Pleven, Bulgaria

Location

Research Site

Mississauga, Ontario, Canada

Location

Research Site

Prague, Czechia

Location

Research Site

Hamburg, Germany

Location

Research Site

Munich, Germany

Location

Research Site

Balatonfüred, Hungary

Location

Research Site

Budapest, Hungary

Location

Research Site

Amsterdam, Netherlands

Location

Research Site

Warsaw, Poland

Location

Research Site

Yaroslavl, Russia

Location

Research Site

Durban, South Africa

Location

Research Site

Pretoria, South Africa

Location

Research Site

Stellenbosch, South Africa

Location

Research Site

Manchester, United Kingdom

Location

Research Site

Oxford, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

fostamatinib; Adalimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dave Goldstraw
• Organization: AstraZeneca Pharmaceuticals

dave.goldstraw@astrazeneca.com

+44 (0)1625 512415

Study Officials

• Neil MacKillop, MD PhD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: March 19, 2014
• First Posted: March 20, 2014
• Study Start: February 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: June 25, 2014
• Results First Posted: June 25, 2014

Record last verified: 2014-04

Locations

HU (2); PL (1); ZA (3); NL (1); CA (1); BU (1); RU (1); US (6); CZ (1); DE (2); GB (2)