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

NCT00603525 | Terminated Phase 3 Results

• 2 other identifiers: 110634GEN411
• Study Type: interventional
• Target: 169
• Locations: 12 countries
• Sites: 60

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.

Conditions

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24

  The ACR score was based on improvement from baseline in tender (TJC) and swollen joint counts (SJC). A participant had achieved ACR20 if he experienced \>=20% improvement from baseline in TJC and SJC and a \>=20% improvement from baseline in 3 out of 5 of the following assessments: participant pain assessment on a 100 millimeter (mm) visual analog scale (VAS), participant global assessment on a 100 mm VAS scale, physician global assessment on a 100 mm VAS scale, participant self-assessed disability, and C-reactive protein.

  Baseline and Week 24

Secondary Outcomes (48)

• Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Weeks 4, 8, 12, 16, and 20

  Baseline and Weeks 4, 8, 12, 16, and 20

• Number of Participants With a 50% Improvement From Baseline in Their ACR Score (ACR50) at Weeks 4, 8, 12, 16, 20, and 24

  Baseline and Weeks 4, 8, 12, 16, 20, and 24

• Number of Participants With a 70% Improvement From Baseline in Their ACR Score (ACR70) at Weeks 4, 8, 12, 16, 20, and 24

  Baseline and Weeks 4, 8, 12, 16, 20, and 24

• Mean Disease Activity Score Based on 28 Joints (DAS28) at Weeks 4, 8, 12, 16, 20, and 24 Using C-reactive Protein (CRP) as the Acute Phase Reactant (APR)

  Weeks 4, 8, 12, 16, 20, and 24

• Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant

  Baseline and Weeks 4, 8, 12, 16, 20, and 24

Study Arms (2)

Ofatumumab

EXPERIMENTAL

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

Drug: Ofatumumab

1000 ml Saline

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Ofatumumab 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

Ofatumumab

Placebo 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

1000 ml Saline

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (60)

GSK Investigational Site

Ciudad Autónoma de Buenos Aires, Buenos Aires, AAL1426, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, 2000, Argentina

Location

GSK Investigational Site

Córdoba, 5000, Argentina

Location

GSK Investigational Site

San Miguel de Tucumán, 4000, Argentina

Location

GSK Investigational Site

Herlev, 2730, Denmark

Location

GSK Investigational Site

Silkeborg, 8600, Denmark

Location

GSK Investigational Site

Amiens, Picardie, 80054, France

Location

GSK Investigational Site

Cahors, 46005, France

Location

GSK Investigational Site

Corbeil-Essonnes, 91106, France

Location

GSK Investigational Site

Échirolles, 38434, France

Location

GSK Investigational Site

Strasbourg, 67098, France

Location

GSK Investigational Site

Toulouse, 31059, France

Location

GSK Investigational Site

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

GSK Investigational Site

Erlangen, Bavaria, 91054, Germany

Location

GSK Investigational Site

Potsdam, Brandenburg, 14467, Germany

Location

GSK Investigational Site

Hamburg, Hamburg, 22081, Germany

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GSK Investigational Site

Hamburg, Hamburg, 22415, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Osnabrück, Lower Saxony, 49074, Germany

Location

GSK Investigational Site

Leipzg, Saxony, 04109, Germany

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GSK Investigational Site

Magdeburg, Saxony-Anhalt, 39112, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 10559, Germany

Location

GSK Investigational Site

Berlin, State of Berlin, 14129, Germany

Location

GSK Investigational Site

Napoli, Campania, 80131, Italy

Location

GSK Investigational Site

Telese Terme (BN), Campania, 82100, Italy

Location

GSK Investigational Site

Rome, Lazio, 00161, Italy

Location

GSK Investigational Site

Genoa, Liguria, 16132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20132, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20162, Italy

Location

GSK Investigational Site

Varese, Lombardy, 21100, Italy

Location

GSK Investigational Site

Prato, Tuscany, 59100, Italy

Location

GSK Investigational Site

Padua, Veneto, 35121, Italy

Location

GSK Investigational Site

Amsterdam, 1056 AB, Netherlands

Location

GSK Investigational Site

Enschede, 7511JX, Netherlands

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GSK Investigational Site

Zwolle, 8011 JW, Netherlands

Location

GSK Investigational Site

Haugesund, N-5528, Norway

Location

GSK Investigational Site

Levanger, 7600, Norway

Location

GSK Investigational Site

Lillehammer, 2609, Norway

Location

GSK Investigational Site

Trondheim, 7006, Norway

Location

GSK Investigational Site

Lima, Lima Province, Lima 27, Peru

Location

GSK Investigational Site

Incheon, 400-711, South Korea

Location

GSK Investigational Site

Seoul, 110-744, South Korea

Location

GSK Investigational Site

Seoul, 120-752, South Korea

Location

GSK Investigational Site

Seoul, 133-792, South Korea

Location

GSK Investigational Site

Seoul, 137-701, South Korea

Location

GSK Investigational Site

Getafe/Madrid, 28905, Spain

Location

GSK Investigational Site

Madrid, 28007, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Mérida (Badajoz), 06800, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Seville, 41071, Spain

Location

GSK Investigational Site

Valencia, 46017, Spain

Location

GSK Investigational Site

Oskarström, SE-313 92, Sweden

Location

GSK Investigational Site

Stockholm, SE-171 76, Sweden

Location

GSK Investigational Site

Wishaw, Lanarkshire, ML2 0DP, United Kingdom

Location

GSK Investigational Site

Newcastle, Northumberland, NE1 4LP, United Kingdom

Location

GSK Investigational Site

Cannock, WS11 5XY, United Kingdom

Location

GSK Investigational Site

Dundee, DD1 9SY, United Kingdom

Location

GSK Investigational Site

Leytonstone, London, E11 1NR, United Kingdom

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

ofatumumab

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: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: January 16, 2008
• First Posted: January 29, 2008
• Study Start: January 1, 2008
• Primary Completion: March 1, 2011
• Study Completion: July 1, 2013
• Last Updated: June 9, 2014
• Results First Posted: November 28, 2011

Record last verified: 2014-04

Locations

ES (7); DE (11); NO (4); IT (10); NL (3); GB (5); SE (2); KR (5); FR (6); DK (2); AR (4); PE (1)