Last updated: 11/07/2018 03:01:01

Investigating clinical efficacy of ofatumumab in adult Rheumatoid Arthritis (RA) patients who had an inadequate response to TNF-α antagonist therapy

GSK study ID
110634
See study documents
Clinicaltrials.gov ID
NCT00603525
See results summary
EudraCT ID
2007-002951-18
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with a 20% improvement from baseline in their American College of Rheumatology (ACR) score (ACR20) at Week 24

Timeframe: Baseline and Week 24

Secondary outcomes:

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

Timeframe: 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

Timeframe: 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

Timeframe: 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)

Timeframe: 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

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

Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 using erythrocyte sedimentation rate (ESR) as the acute phase reactant (ARP)

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

Change from baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 using ESR as the acute phase reactant

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

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

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

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

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

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

Change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) score at Weeks 4, 8, 12, 16, 20, and 24

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

Change from baseline in tender joint count at Week 24

Timeframe: Baseline and Week 24

Change from baseline in swollen joint count at Week 24

Timeframe: Baseline and Week 24

Change from baseline in CRP at Week 24

Timeframe: Baseline and Week 24

Change from baseline in ESR at Week 24

Timeframe: Baseline and Week 24

Change from baseline in the participant-assessed pain score using visual analogue scale (VAS) at Week 24

Timeframe: Baseline and Week 24

Change from baseline in participant-assessed global disease score using VAS at Week 24

Timeframe: Baseline and Week 24

Change from baseline in the physician-assessed global disease score using VAS at Week 24

Timeframe: Baseline and Week 24

Change from baseline in the functional assessment of chronic illness therapy (FACIT) questionnaire score at Week 24

Timeframe: 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

Timeframe: Baseline and Week 24

Change from baseline in the SF-36v2 norm-based scores for mental component summary and mental items at Week 24

Timeframe: Baseline and Week 24

Biomarker levels for Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at baseline and Week 4

Timeframe: Baseline and Week 4

Number of participants with positive human anti-human antibodies (HAHA) at Week 24

Timeframe: Baseline and Week 24

Change from baseline in levels of IgA, IgG and IgM at Week 12 and Week 24

Timeframe: Baseline, Week 12, and Week 24

Minimum DAS28-ESR score during the DB and OL Periods, by ofatumumab treatment course

Timeframe: First 24 weeks of each treatment course (assessed up to Week 144)

Minimum DAS28-CRP score during the DB and OL Periods, by ofatumumab treatment course

Timeframe: First 24 weeks of each treatment course (assessed up to Week 144)

Minimum change from baseline DAS28-ESR Score, during the DB and OL Periods, by ofatumumab treatment course

Timeframe: First 24 weeks of each treatment course (assessed up to Week 144)

Minimum change from baseline DAS28-CRP Score, during the DB and OL Periods, by ofatumumab treatment course

Timeframe: First 24 weeks of each treatment course (assessed up to Week 144)

Time to retreatment, by ofatumumab treatment course

Timeframe: From Baseline up to Week 144

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

Timeframe: First 24 weeks of each treatment course (assessed up to Week 144)

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

Timeframe: First 24 weeks of each treatment course (assessed up to Week 144)

Number of participants with any on-treatment adverse event or serious adverse event, during the DB and OL Periods, by ofatumumab treatment course

Timeframe: First treatment (Day 0) until the participant terminated the trial, assessed up to Week 144

Number of participants with the indicated electrocardiogram (ECG) findings, during the OL Period

Timeframe: From DB Period completion (Week 24) until the completion of the OL Period, 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

Timeframe: From baseline up to Week 144

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

Timeframe: From baseline up to Week 144

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

Timeframe: From baseline 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

Timeframe: From baseline up to Week 144

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

Timeframe: From baseline up to Week 144

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

Timeframe: 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

Timeframe: From baseline up to Week 144

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

Timeframe: From baseline up to Week 144

Number of participants with positive John Cunningham (JC) Virus test results at baseline or any visit post-baseline during the DB and OL Periods

Timeframe: From basline up to Week 144

Number of participants with any serious adverse event during the Follow-up Period

Timeframe: 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 immunoglobulin values outside the reference range during the Follow-up Period

Timeframe: 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)

Time to first CD19+ B-cell repopulation relative to the first dose and last dose of ofatumumab

Timeframe: From the first dose of ofatumumab until the last Follow-up Period visit (up to Week 248)

Number of participants with a positive JC Virus test result during the Follow-up Period

Timeframe: 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 clinical chemistry values of potential clinical concern during the Follow-up Period

Timeframe: 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 the indicated hematology values of potential clinical concern during the Follow-up Period

Timeframe: 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)

Interventions:
  • Drug: Ofatumumab
  • Drug: Placebo
    • Enrollment:
    169
    Primary completion date:
    2011-01-03
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Emilia Quattrocchi, Mikkel Østergaard, Peter C. Taylor, Ronald F. van Vollenhoven, Myron Chu, Stephen Mallett, Hayley Perry, Regina Kurrasch. Safety of Repeated Open-label Treatment Courses of Intravenous Ofatumumab, a Human Anti-CD20 Monoclonal Antibody, in Rheumatoid Arthritis: Results from Three Clinical Trials. PLoS ONE.2016
    Medical condition
    Arthritis, Rheumatoid
    Product
    ofatumumab
    Collaborators
    Not applicable
    Study date(s)
    January 2008 to July 2013
    Type
    Interventional
    Phase
    2/3

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Age ≥ 18 years;
    • Active disease at the time of screening as defined by:
    • Patients with a history of a rheumatic autoimmune disease other than RA
    • or with significant systemic involvement secondary to RA;
    Inclusion and 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.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Napoli, Campania, Italy, 80131
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Cordoba, Argentina, 5000
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Seoul, South Korea, 120-752
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Telese Terme (BN), Campania, Italy, 82100
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Milano, Lombardia, Italy, 20157
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Echirolles, France, 38434
    Status
    Study Complete
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    Showing 1 - 6 of 57 Results

    Study documents

    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2011-01-03
    Actual study completion date
    2013-15-07

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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