Investigating Clinical Efficacy of Ofatumumab in Adult Rheumatoid Arthritis (RA) Patients Who Had an Inadequate Response to TNF-α Antagonist Therapy

NCT ID: NCT00603525

Last Updated: 2014-06-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 169 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2013-07-31

Brief Summary

This is a phase III, double-blind, randomized, multicenter, and parallel group trial with a duration of 24 weeks, followed by a 120 week Open-label Period. The primary purpose of the study is to demonstrate the efficacy and safety of ofatumumab in reducing clinical signs and symptoms in adult RA patients who had an inadequate response to TNF-α antagonist therapy.

Detailed Description

This study consist of a double-blind, placebo controlled, and parallel group part with eligible patients enrolled into a 24 week Double-Blind Period, and randomized in a 1:1 ratio to receive either ofatumumab or placebo in addition to their background methotrexate treatment. Patients who complete the 24 week Double-blind Period without receiving rescue DMARD treatment will then be eligible to proceed into the 120 week Open-label Period to receive repeat treatment courses with ofatumumab. In the Open-label Period ofatumumab treatment courses will be given at individualized time intervals only if a clinical response has been achieved following the previous treatment course, and followed by a subsequent worsening in disease activity.

Patients who have completed the Open-label Period or have been withdrawn will then enter a maximum 2 year Follow-up Period, or until there B-cells return to normal or to baseline levels, whichever occurs earlier

Conditions

Arthritis, Rheumatoid

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ofatumumab

1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each treatment cycle consisting of two IV infusion taken 14 days apart. A total of 8 infusion cycles given over a 144 week period

Group Type: EXPERIMENTAL

Ofatumumab

Intervention Type: DRUG

1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each treatment cycle consisting of two IV infusion taken 14 days apart. A total of 8 infusion cycles given over a 144 week period

1000 ml Saline

1000 mL sterile, pyrogen free 0.9% NaCl. A treatment cycle consisting of two IV infusion taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1000 mL sterile, pyrogen free 0.9% NaCl. A treatment cycle consisting of two IV infusion taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period

Interventions

Ofatumumab

1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each treatment cycle consisting of two IV infusion taken 14 days apart. A total of 8 infusion cycles given over a 144 week period

Intervention Type: DRUG

Placebo

1000 mL sterile, pyrogen free 0.9% NaCl. A treatment cycle consisting of two IV infusion taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years;
• Active disease at the time of screening as defined by:

≥ 8 swollen joints (of 66 joints assessed) and ≥ 8 tender joints (of 68 joints assessed), C-Reactive Protein (CRP) ≥ 1.0 mg/dL or Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/hour, DAS28≥3.2 (based on ESR);

• Inadequate response to previous or current TNF-alpha antagonist treatment;
• Treatment with methotrexate (MTX), 7.5-25 mg/week, for at least 12 weeks and at a stable dose for at least 4 weeks.

Exclusion Criteria

• Patients with a history of a rheumatic autoimmune disease other than RA or with significant systemic involvement secondary to RA;
• Previous exposure to biologic anti-rheumatic therapies, including investigational compounds;
• Exposure to TNF-alpha antagonist treatment < 12 weeks prior to visit 2;
• Chronic or ongoing active infectious disease requiring systemic treatment;
• Clinically significant cardiac disease; History of significant cerebrovascular disease;
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease, or evidence of demyelinating disease;
• Known HIV positive; Serologic evidence of Hepatitis B infection; Positive test for Hepatitis C; Positive plasma / white cell JC Virus PCR;
• Serum IgG < lower limit of normal;
• Breast feeding women or women with a positive pregnancy test at screening;
• Current participation in any other interventional clinical study;
• Patients known or suspected of not being able to comply with a study protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Córdoba, , Argentina

GSK Investigational Site

San Miguel de Tucumán, , Argentina

GSK Investigational Site

Herlev, , Denmark

GSK Investigational Site

Silkeborg, , Denmark

GSK Investigational Site

Amiens, Picardie, France

GSK Investigational Site

Cahors, , France

GSK Investigational Site

Corbeil-Essonnes, , France

GSK Investigational Site

Échirolles, , France

GSK Investigational Site

Strasbourg, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, Germany

GSK Investigational Site

Erlangen, Bavaria, Germany

GSK Investigational Site

Potsdam, Brandenburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Osnabrück, Lower Saxony, Germany

GSK Investigational Site

Leipzg, Saxony, Germany

GSK Investigational Site

Magdeburg, Saxony-Anhalt, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Napoli, Campania, Italy

GSK Investigational Site

Telese Terme (BN), Campania, Italy

GSK Investigational Site

Rome, Lazio, Italy

GSK Investigational Site

Genoa, Liguria, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Varese, Lombardy, Italy

GSK Investigational Site

Prato, Tuscany, Italy

GSK Investigational Site

Padua, Veneto, Italy

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Enschede, , Netherlands

GSK Investigational Site

Zwolle, , Netherlands

GSK Investigational Site

Haugesund, , Norway

GSK Investigational Site

Levanger, , Norway

GSK Investigational Site

Lillehammer, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Lima, Lima Province, Peru

GSK Investigational Site

Incheon, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Seoul, , South Korea

GSK Investigational Site

Getafe/Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Mérida (Badajoz), , Spain

GSK Investigational Site

Santander, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Oskarström, , Sweden

GSK Investigational Site

Stockholm, , Sweden

GSK Investigational Site

Wishaw, Lanarkshire, United Kingdom

GSK Investigational Site

Newcastle, Northumberland, United Kingdom

GSK Investigational Site

Cannock, , United Kingdom

GSK Investigational Site

Dundee, , United Kingdom

GSK Investigational Site

Leytonstone, London, , United Kingdom

Countries

Argentina; Denmark; France; Germany; Italy; Netherlands; Norway; Peru; South Korea; Spain; Sweden; United Kingdom

Other Identifiers

GEN411

Identifier Type: OTHER

Identifier Source: secondary_id

110634

Identifier Type: -

Identifier Source: org_study_id