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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00611455




Registration number
NCT00611455
Ethics application status
Date submitted
16/01/2008
Date registered
11/02/2008
Date last updated
6/11/2017

Titles & IDs
Public title
Investigating Clinical Efficacy of Ofatumumab in Adult Rheumatoid Arthritis (RA) Patients Who Had an Inadequate Response to MTX Therapy
Scientific title
A Double-blind, Randomized, Placebo Controlled, Parallel Group, Multi-center, Phase III Trial of Ofatumumab Investigating Clinical Efficacy in Adult Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
Secondary ID [1] 0 0
GEN410
Secondary ID [2] 0 0
110635
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arthritis, Rheumatoid 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ofatumumab
Treatment: Drugs - Placebo

Experimental: ofatumumab - 1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two 700mg IV infusions taken 14 days apart. A total of 8 infusions cycles given over a 144 week period

Placebo comparator: 1000 ml Saline - 1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two IV infusions taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period


Treatment: Drugs: ofatumumab
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two 700mg IV infusions taken 14 days apart. A total of 8 infusions cycles given over a 144 week period

Treatment: Drugs: Placebo
1000 mL dilution of 35ml of ofatumumab in sterile, pyrogen free 0.9% NaCl. Each Treatment Cycle consisting of two IV infusions taken 14 days apart. Only one placebo treatment cycle provided over a 24 week period
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With a 20% Improvement From Baseline in Their American College of Rheumatology (ACR) Score (ACR20) at Week 24
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Baseline and Weeks 4, 8, 12, 16, and 20
Secondary outcome [2] 0 0
Number of Participants With a 50% Improvement From Baseline in Their ACR Score (ACR50) at Weeks 4, 8, 12, 16, 20, and 24
Timepoint [2] 0 0
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [3] 0 0
Number of Participants With a 70% Improvement From Baseline in Their ACR Score (ACR70) at Weeks 4, 8, 12, 16, 20, and 24
Timepoint [3] 0 0
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [4] 0 0
Median ACRn at Weeks 4, 8, 12, 16, 20, and 24
Timepoint [4] 0 0
Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [5] 0 0
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)
Timepoint [5] 0 0
Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [6] 0 0
Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using CRP as the Acute Phase Reactant
Timepoint [6] 0 0
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [7] 0 0
Mean DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using Erythrocyte Sedimentation Rate (ESR) as the Acute Phase Reactant
Timepoint [7] 0 0
Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [8] 0 0
Change From Baseline in DAS28 at Weeks 4, 8, 12, 16, 20, and 24 Using ESR as the Acute Phase Reactant
Timepoint [8] 0 0
Baseline and Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [10] 0 0
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
Timepoint [10] 0 0
Weeks 4, 8, 12, 16, 20, and 24
Secondary outcome [11] 0 0
Number of Participants Classified as Responders at Week 24 According to the Self-Assessed Health Assessment Questionnaire Disability Index (HAQ-DI)
Timepoint [11] 0 0
Week 24
Secondary outcome [12] 0 0
Number of Participants With Clinical Remission at Week 24
Timepoint [12] 0 0
Week 24
Secondary outcome [13] 0 0
Change From Baseline in Tender Joint Count at Week 24
Timepoint [13] 0 0
Baseline and Week 24
Secondary outcome [14] 0 0
Change From Baseline in Swollen Joint Count at Week 24
Timepoint [14] 0 0
Baseline and Week 24
Secondary outcome [15] 0 0
Change From Baseline in the Participant-assessed Pain Score at Week 24
Timepoint [15] 0 0
Baseline and Week 24
Secondary outcome [16] 0 0
Change From Baseline in Participant-assessed Global Disease Score at Week 24
Timepoint [16] 0 0
Baseline and Week 24
Secondary outcome [17] 0 0
Change From Baseline in the Physician-assessed Global Disease Score at Week 24
Timepoint [17] 0 0
Baseline and Week 24
Secondary outcome [18] 0 0
Change From Baseline in HAQ-DI Score at Week 24
Timepoint [18] 0 0
Baseline and Week 24
Secondary outcome [19] 0 0
Change From Baseline in CRP at Week 24
Timepoint [19] 0 0
Baseline and Week 24
Secondary outcome [20] 0 0
Change From Baseline in ESR at Week 24
Timepoint [20] 0 0
Baseline and Week 24
Secondary outcome [21] 0 0
Change From Baseline in the Short-Form 36 (SF-36v2) Norm-based Scores for Physical Component Summary and Physical Items at Week 24
Timepoint [21] 0 0
Baseline and Week 24
Secondary outcome [22] 0 0
Change From Baseline in the SF-36v2 Norm-based Scores for Mental Component Summary and Mental Items at Week 24
Timepoint [22] 0 0
Baseline and Week 24
Secondary outcome [23] 0 0
Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT) Questionnaire Score at Week 24
Timepoint [23] 0 0
Baseline and Week 24
Secondary outcome [24] 0 0
Change From Baseline in Levels of Anti-CCP, RF-IgA, RF-IgG, and RF-IgM at Week 24
Timepoint [24] 0 0
Baseline and Week 24
Secondary outcome [25] 0 0
Change From Baseline in Levels of IL-6 and Serum Amyloid A at Week 24
Timepoint [25] 0 0
Baseline and Week 24
Secondary outcome [26] 0 0
Minimum DAS28-ESR Score During the Double-blind (DB) and Open-label (OL) Periods, by Ofatumumab Treatment Course
Timepoint [26] 0 0
First 24 weeks of each treatment course (assessed up to Week 144)
Secondary outcome [27] 0 0
Minimum DAS28-CRP Score During the DB and OL Periods, by Ofatumumab Treatment Course
Timepoint [27] 0 0
First 24 weeks of each treatment course (assessed up to Week 144)
Secondary outcome [28] 0 0
Minimum Change From Baseline in the DAS28-ESR Score, During the DB and OL Periods, by Ofatumumab Treatment Course
Timepoint [28] 0 0
First 24 weeks of each treatment course (assessed up to Week 144)
Secondary outcome [29] 0 0
Minimum Change From Baseline in the DAS28-CRP Score, During the DB and OL Periods, by Ofatumumab Treatment Course
Timepoint [29] 0 0
First 24 weeks of each treatment course (assessed up to Week 144)
Secondary outcome [30] 0 0
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
Timepoint [30] 0 0
First 24 weeks of each treatment course (assessed up to Week 144)
Secondary outcome [31] 0 0
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
Timepoint [31] 0 0
First 24 weeks of each treatment course (assessed up to Week 144)
Secondary outcome [32] 0 0
Time to Retreatment, by Ofatumumab Treatment Course
Timepoint [32] 0 0
From Baseline up to Week 144
Secondary outcome [33] 0 0
Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event, During the DB and OL Periods, by Ofatumumab Treatment Course
Timepoint [33] 0 0
First treatment (Day 0) until the participant terminated the trial, assessed up to Week 144
Secondary outcome [34] 0 0
Number of Participants With a CD19+ 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
Timepoint [34] 0 0
From baseline up to Week 144
Secondary outcome [35] 0 0
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
Timepoint [35] 0 0
From baseline up to Week 144
Secondary outcome [36] 0 0
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
Timepoint [36] 0 0
From baseline up to Week 144
Secondary outcome [37] 0 0
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
Timepoint [37] 0 0
From baseline up to Week 144
Secondary outcome [38] 0 0
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
Timepoint [38] 0 0
From baseline up to Week 144
Secondary outcome [39] 0 0
Number of Participants With the Indicated Electrocardiogram (ECG) Findings, During the OL Period
Timepoint [39] 0 0
From DB Period completion (Week 24) until the completion of the OL Period, assessed up to Week 144
Secondary outcome [40] 0 0
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
Timepoint [40] 0 0
From baseline up to Week 144
Secondary outcome [41] 0 0
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
Timepoint [41] 0 0
From baseline up to Week 144
Secondary outcome [42] 0 0
Number of Participants With the Indicated Biomarker Data Outside the Reference Range at Baseline or Any Post-Baseline Visit During the DB and OL Periods by Ofatumumab Treatment Course (TC)
Timepoint [42] 0 0
From baseline up to Week 144
Secondary outcome [43] 0 0
Number of Participants With Any Serious Adverse Event During the Follow-up Period
Timepoint [43] 0 0
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])
Secondary outcome [44] 0 0
Number of Participants With Immunoglobulin Values Outside the Reference Range During the Follow-up Period
Timepoint [44] 0 0
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)
Secondary outcome [45] 0 0
Time to First CD19+ B-cell Repopulation Relative to the First Dose and Last Dose of Ofatumumab
Timepoint [45] 0 0
From the first dose of ofatumumab until the last Follow-up Period visit (up to Week 248)
Secondary outcome [46] 0 0
Number of Participants With a Positive JC Virus Test Result During the Follow-up Period
Timepoint [46] 0 0
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)
Secondary outcome [47] 0 0
Number of Participants With the Indicated Clinical Chemistry Values of Potential Clinical Concern During the Follow-up Period
Timepoint [47] 0 0
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)
Secondary outcome [48] 0 0
Number of Participants With the Indicated Hematology Values of Potential Clinical Concern During the Follow-up Period
Timepoint [48] 0 0
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)

Eligibility
Key inclusion 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 methotrexate 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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;
* Previous exposure to biologic DMARDs; 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/01/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
15/07/2013
Sample size
Target
Accrual to date
Final
265
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Camperdown
Recruitment hospital [2] 0 0
GSK Investigational Site - Maroochydore
Recruitment hospital [3] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [4] 0 0
GSK Investigational Site - Malvern
Recruitment hospital [5] 0 0
GSK Investigational Site - Shenton Park
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4558 - Maroochydore
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
6008 - Shenton Park
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Santa Fe
Country [3] 0 0
Argentina
State/province [3] 0 0
Cordoba
Country [4] 0 0
Argentina
State/province [4] 0 0
Tucuman
Country [5] 0 0
Belgium
State/province [5] 0 0
Liège
Country [6] 0 0
Belgium
State/province [6] 0 0
Merksem
Country [7] 0 0
Chile
State/province [7] 0 0
Región Metro De Santiago
Country [8] 0 0
Chile
State/province [8] 0 0
Valparaíso
Country [9] 0 0
Czechia
State/province [9] 0 0
Ostrava Trebovice
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 2
Country [11] 0 0
Czechia
State/province [11] 0 0
Zlin
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Hungary
State/province [13] 0 0
Gyor
Country [14] 0 0
Peru
State/province [14] 0 0
Callao
Country [15] 0 0
Peru
State/province [15] 0 0
Lima
Country [16] 0 0
Poland
State/province [16] 0 0
Bialystok
Country [17] 0 0
Poland
State/province [17] 0 0
Bydgoszcz
Country [18] 0 0
Poland
State/province [18] 0 0
Warszawa
Country [19] 0 0
Poland
State/province [19] 0 0
Wroclaw
Country [20] 0 0
Romania
State/province [20] 0 0
Bucuresti
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Ekaterinburg
Country [22] 0 0
Russian Federation
State/province [22] 0 0
Moscow
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Saint-Petersburg
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Saratov
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Yaroslavl
Country [26] 0 0
South Africa
State/province [26] 0 0
Gauteng
Country [27] 0 0
South Africa
State/province [27] 0 0
Parow
Country [28] 0 0
Spain
State/province [28] 0 0
Granada
Country [29] 0 0
Spain
State/province [29] 0 0
Malaga
Country [30] 0 0
Spain
State/province [30] 0 0
Santander
Country [31] 0 0
Spain
State/province [31] 0 0
Sevilla
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Lancashire
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Cannock
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Leytonstone, London
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Maidstone

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
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 of ofatumumab in reducing clinical signs and symptoms in adult RA patients after a single course of ofatumumab.
Trial website
https://clinicaltrials.gov/study/NCT00611455
Trial related presentations / publications
Taylor PC, Quattrocchi E, Mallett S, Kurrasch R, Petersen J, Chang DJ. Ofatumumab, a fully human anti-CD20 monoclonal antibody, in biological-naive, rheumatoid arthritis patients with an inadequate response to methotrexate: a randomised, double-blind, placebo-controlled clinical trial. Ann Rheum Dis. 2011 Dec;70(12):2119-25. doi: 10.1136/ard.2011.151522. Epub 2011 Aug 22.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00611455