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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00603525
• Date of registration: 16/01/2008
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Investigating Clinical Efficacy of Ofatumumab in Adult Rheumatoid Arthritis (RA) Patients Who Had an Inadequate Response to TNF-a Antagonist Therapy
• Scientific title: A Double-blind, Randomized, Placebo Controlled, Parallel Group, Multi-center, Phase III Trial of Ofatumumab Investigating Clinical Efficacy in Patients With Active Rheumatoid Arthritis Who Have Previously Had an Inadequate Response to One or More TNF Antagonist Therapies
• Date of first enrolment: January 2008
• Target sample size: 169
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00603525
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

Argentina, Denmark, France, Germany, Italy, Korea, Republic of, Netherlands, Norway, Peru, Spain, Sweden, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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.



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

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: Placebo

Drug: Ofatumumab

Primary Outcome(s)

Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24 [Time Frame: Baseline and Week 24]

Secondary Outcome(s)

Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Change From Baseline in Participant-assessed Global Disease Score Using VAS at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in CRP at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Swollen Joint Count at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in the Short-Form 36 (SF-36v2) Norm-based Scores for Physical Component Summary and Physical Items at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Tender Joint Count at Week 24 [Time Frame: Baseline and Week 24]

Median of the Largest Integer n, for Which a Participant Met the ACR Criteria Requiring an Improvement of n% (ACRn) at Weeks 4, 8, 12, 16, 20, and 24 [Time Frame: Weeks 4, 8, 12, 16, 20, and 24]

Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Questionnaire Score at Week 24 [Time Frame: Baseline and Week 24]

Minimum DAS28-ESR Score During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First 24 weeks of each treatment course (assessed up to Week 144)]

Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using Erythrocyte Sedimentation Rate (ESR) as the Acute Phase Reactant (ARP) [Time Frame: Weeks 4, 8, 12, 16, 20, and 24]

Change From Baseline in the Physician-assessed Global Disease Score Using VAS at Week 24 [Time Frame: Baseline and Week 24]

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

Minimum Change From Baseline DAS28-ESR Score, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First 24 weeks of each treatment course (assessed up to Week 144)]

Number of Participants With a CD19+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at Indicated the Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Biomarker Levels for Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at Baseline and Week 4 [Time Frame: Baseline and Week 4]

Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Weeks 4, 8, 12, 16, 20, and 24 [Time Frame: Weeks 4, 8, 12, 16, 20, and 24]

Minimum DAS28-CRP Score During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First 24 weeks of each treatment course (assessed up to Week 144)]

Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern During the Follow-up Period [Time Frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years)]

Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First treatment (Day 0) until the participant terminated the trial, assessed up to Week 144]

Number of Participants With Any Serious Adverse Event During the Follow-up Period [Time Frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from Last Subject Last Visit [LSLV])]

Number of Participants With a CD3+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Number of Participants With Positive Human Anti-human Antibodies (HAHA) at Week 24 [Time Frame: Baseline and Week 24]

Number of Participants With a CD4+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point , During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Number of Participants With a Positive JC Virus Test Result During the Follow-up Period [Time Frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV)]

Number of Participants With Positive John Cunningham (JC) Virus Test Results at Baseline or Any Visit Post-baseline During the DB and OL Periods [Time Frame: From basline up to Week 144]

Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24]

Number of Participants With the Indicated Hematology Values of Potential Clinical Concern at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Number of Participants With Vital Sign Data Outside the Clinical Concern Range at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Time to First CD19+ B-cell Repopulation Relative to the First Dose and Last Dose of Ofatumumab [Time Frame: From the first dose of ofatumumab until the last Follow-up Period visit (up to Week 248)]

Change From Baseline in ESR at Week 24 [Time Frame: Baseline and Week 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) [Time Frame: Weeks 4, 8, 12, 16, 20, and 24]

Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using ESR), During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First 24 weeks of each treatment course (assessed up to Week 144)]

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 [Time Frame: Baseline and Weeks 4, 8, 12, 16, and 20]

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

Number of Participants With Immunoglobulin Values Outside the Reference Range at Baseline or Any Visit Post-baseline, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24]

Change From Baseline in Levels of IgA, IgG and IgM at Week 12 and Week 24 [Time Frame: Baseline, Week 12, and Week 24]

Change From Baseline in the Participant-assessed Pain Score Using Visual Analogue Scale (VAS) at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in the SF-36v2 Norm-based Scores for Mental Component Summary and Mental Items at Week 24 [Time Frame: Baseline and Week 24]

Minimum Change From Baseline DAS28-CRP Score, During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First 24 weeks of each treatment course (assessed up to Week 144)]

Number of Participants With Immunoglobulin Values Outside the Reference Range During the Follow-up Period [Time Frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (or maximum of 2 years from LSLV)]

Number of Participants With the Indicated Hematology Values of Potential Clinical Concern During the Follow-up Period [Time Frame: From the last scheduled visit in the DB or OL Period until B-cells and circulating IgG had returned to normal or baseline levels (maximum of 2 years)]

Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24]

Number of Participants Who Achieved Remission or Low Disease Activity Based on DAS28 (Using CRP), During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: First 24 weeks of each treatment course (assessed up to Week 144)]

Number of Participants With a CD8+ Cell Count Greater Than or Equal to the Lower Limit of Normal or the Baseline Value at the Indicated Time Point , During the DB and OL Periods, by Ofatumumab Treatment Course [Time Frame: From baseline up to Week 144]

Number of Participants With the Indicated Electrocardiogram (ECG) Findings, During the OL Period [Time Frame: From DB Period completion (Week 24) until the completion of the OL Period, assessed up to Week 144]

Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant [Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, and 24]

Time to Retreatment, by Ofatumumab Treatment Course [Time Frame: From Baseline up to Week 144]

Secondary ID(s)

GEN411

110634

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 28/11/2011
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00603525