Arthritis, RheumatoidPhase 2NCT00655824
Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403
A Phase 2 study testing ofatumumab in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 10 sites in 5 countries.
Trial summary
A 3-year open-label trial for patients who previously participated in Trial Hx-CD20-403 and who fulfill the eligibility criteria for this trial (GEN413) . Th e primary purpose of the trial is to evaluate the long-term effectiveness of repeated courses ( a maximum of 9 treatment courses) of ofatumumab in RA patients… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- ofatumumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 1 Jan 2008to 19 Mar 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previously received ofatumumab or placebo in Trial Hx-CD20-403.
- Patients on methotrexate therapy (7.5 - 25 mg/week, p.o., i.m., and/or s.c.).
- Oral corticosteroids therapy (≤ 10 mg/day prednisolone or equivalent).
- Active disease at the time of screening as defined by:
- 3 swollen joints (of 28 joints assessed) and ≥ 3 tender joints (of 28 joints assessed), DAS28≥3.2 (based on ESR)
Who cannot join
- Use of DMARDs other than methotrexate or exposure to other cell depleting therapy, including investigational compounds < 6 months prior to Visit 2 A.
- Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening).
- Breast feeding women or women with a positive pregnancy test at Visit 1 (screening).
- Received anti-cancer therapy, corticosteroids (intra-articular, i.m., or i.v.), or live/attenuated vaccinations, or exposure to cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents < 5 years prior to screening.
- Past or current malignancy, except for Cervical carcinoma Stage 1B or less, Non-invasive basal cell and squamous cell skin carcinoma, Malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years.
- Chronic or ongoing active infectious disease requiring systemic treatment.
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- Clinically significant cardiac disease, or history of significant cerebrovascular disease.
- Significant concurrent, uncontrolled medical conditions, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral psychiatric disease
- Known or suspected HIV positive, positive serology for hepatitis B (HB), positive test for Hepatitis C, or positive plasma or white cell JC virus (JCV) PCR (either compartment).
- A circulating IgG level <lower limit of normal.
- Known hypersensitivity to components of the investigational medicinal product.
- Patients known or suspected of not being able to comply with a study protocol.
- Women of child bearing potential not will to use adequate contraception during study
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
United States4 sites
GSK Investigational Site
Duncansville, Pennsylvania, 16635
GSK Investigational Site
Fort Lauderdale, Florida, 33334
GSK Investigational Site
Los Angeles, California, 90095
GSK Investigational Site
New York, New York, 10003
Denmark3 sites
GSK Investigational Site
Copenhagen, 2100
GSK Investigational Site
Glostrup Municipality, 2600
GSK Investigational Site
Hellerup, 2900
About this study
Official title: An Open-label, International, Multi-center, Phase II, Extension Trial Investigating Long-term Efficacy and Safety of Repeated Treatment Courses of Ofatumumab, a Fully Human Monoclonal Anti-CD20 Antibody, in Adult Patients With Active Rheumatoid Arthritis Who Previously Received Ofatumumab or Placebo
A 3-year open-label trial for patients who previously participated in Trial Hx-CD20-403 and who fulfill the eligibility criteria for this trial (GEN413) . Th e primary purpose of the trial is to evaluate the long-term effectiveness of repeated courses ( a maximum of 9 treatment courses) of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403.
Read the detailed description
All patients who fulfill the eligibility criteria for this trial , will initiate at least one treatment course of ofatumumab, and depending of subsequent worsening in disease activity will be eligible to received further treatment through the 156 week treatment period: a maximum of a further 8 treatment courses will be given at individualized time intervals . The interval between each treatment course will be at least 16 weeks with the last treatment course given no later than week 130 after baseline (Visit 2A).
After each treatment course the patients will attend their next trial visit 8 weeks after Infusion 1, followed by trial visits every 4 weeks up to Week 24, and subsequently every 8 weeks until the next treatment course.
After completing the Treatment Period or after withdrawing from the Treatment Period prematurely patients will be followed every 12 weeks (Follow-up Period) until CD19+ cells \&/or IgG levels have returned to baseline or normal levels.
- Conditions
- Arthritis, Rheumatoid
- Being tested
- ofatumumab
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ofatumumabDrug
1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl
| Study group | Role | What they receive |
|---|---|---|
| Ofatumumab | Experimental | 1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl Receives: Drug: ofatumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Treatment Withdrawal
Time to treatment withdrawal was defined as the time from the first infusion of ofatumumab until the date of treatment withdrawal. The sponsor discontinued the intravenous route of administration development program for rheumatoid arthritis (RA), and this study was terminated early; hence, this primary endpoint was not evaluated.
Measured: From Baseline up to 144 weeks
Secondary outcomes (30)
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour)
DAS28(ESR) is a numeric outcome that measures RA activity based on the ESR (a non-specific general indicator of inflammation), tender joint count (JC), swollen JC, and participant's global assessment of disease activity on a 100 millimeter Visual Analog Scale. DAS28 values range from 0 (no activity) and upwards; increasing values indicate increasing activity (there is no upper limit on the scale). Change from baseline (CFB) was calculated at all visits; however, minimum CFB was calculated as the minimum CFB obtained over the course of weeks 1-24 of each treatment cycle.
Measured: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP)
DAS28(CRP) is a numeric outcome that measures RA activity based on the CRP (used to monitor acute inflammatory phases of RA), tender JC, swollen JC, and participant's global assessment of disease activity on a 100 millimeter Visual Analog Scale. DAS28 values range from 0 (no activity) and upwards; increasing values indicate increasing activity (there is no upper limit on the scale). Change from baseline (CFB) was calculated at all visits; however, minimum CFB was calculated as the minimum CFB obtained over the course of weeks 1-24 of each treatment cycle.
Measured: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Time to Re-treatment in Each Treatment Course
Time to re-treatment in each treatment course (TC) is defined as the time from the first infusion of ofatumumab until the date of the first infusion of the first re-treatment course. The data presented reflect the time to re-treatment, which is defined as the time in days between the first infusion of each TC and the first infusion of the following TC. For TC 1, time to re-treatment is defined as the time between the first infusion in TC 1 and the first infusion in TC 2; similarly, for TC 2 it is the time between the first infusion of TC 2 and the first infusion of TC 3. The study was terminated by the sponsor after Treatment Course 7; therefore, there are no re-treatment data available for Treatment Course 7.
Measured: Week 16 to Week 104 of each treatment course (up to 125 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Ofatumumab Serum Concentration
Blood samples of participants were collected for the measurement of ofatumumab concentration in the blood. The blood samples were collected before infusion (BI) (baseline of that particular treatment course) and at the end of infusion (EI) of ofatumumab.
Measured: Before infusion and at the end of infusion for each Treatment Course (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next TC; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial vi
Number of Participants Achieving American College of Rheumatology (ACR)20
ACR20 is achieved if the participant has 20% improvement from Baseline in TJC and SJC and in 3 out of 5 of following assessments (A); participant pain A, participant global A, physician global A on a visual analog scale (VAS: a 10 cm scale ranging from "no pain" to "severe pain"; the distance marked by the participant from the "no pain" end is his joint pain score), participant self-assessed disability, and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants Achieving ACR50
ACR50 is achieved if the participant has 50% improvement from Baseline in: TJC and SJC and in 3 out of 5 of following assessment (A) ; participant pain A , participant global A, physician global A on a visual analogue scale (VAS: a 10 cm scale ranges from 'no pain' to 'severe pain' and the distance marked by the participant from the "no pain" end is his joint pain score).and participant self-assessed disability and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TCand 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants Achieving ACR70
ACR70 is achieved if the participant has 70% improvement from Baseline in: TJC and SJC and in 3 out of 5 of following assessment (A) ; participant pain A , participant global A, physician global A on a visual analogue scale (VAS: a 10 cm scale ranges from 'no pain' to 'severe pain' and the distance marked by the participant from the "no pain" end is his joint pain score).and participant self-assessed disability and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response
EULAR response is based on the DAS score. EULAR response criterion classifies participants as good or moderate responders and non-responders. Good response: DAS28 score <=3.2 and >1.2 improvement from Baseline (IfB) in DAS28 score, Moderate response: DAS28 score <=3.2 and between >0.6 and <=1.2 IfB; DAS28 score between >3.2 and <=5.1 and >1.2 IfB; DAS28 score between >3.2 and <=5.1 and between >0.6 and <=1.2 IfB; DAS28 score >5.1 and >1.2 IfB. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants in the Indicated Categories of the Health Assessment Questionnaire (HAQ)
The HAQ, a 20-question instrument, assesses the degree of difficulty a person has in accomplishing tasks in eight functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores). Responses in each area are scored from 0 (no difficulty) to 3 (inability to perform a task in that area). The index is calculated by adding all scores, then dividing this score by the total number of components answered. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With the Indicated Global Disease Assessment Using the VAS
The participant and the physician independantly used the VAS for overall assessment of the disease. VAS is used to measure the physician's subjective assessment of the participant's RA disease process at the time of the visit. The scale ranged from 0 (extremely well) to 10 (extremely poor). The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With the Indicated Pain Score
The pain score was assessed using the VAS: a 10 cm scale ranging from "no pain" to "severe pain"; the distance marked by the participant from the "no pain" end is his joint pain score. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With HAHA Response
The host immune response was assessed based on Human Anti-Human Antibodies (HAHA). The serum samples of the participants were collected for the assessment of HAHA. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Whole Blood Transcriptional Profiles
Blood samples were collected for transcriptomic analysis of messenger ribonucleic acid (mRNA). The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood
Blood samples of participants were collected for the evaluation of CD19+, CD4+, CD3+, and CD8+ B-cell subsets. These biomarkers are associated with immune functions.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3
Blood samples of participants were collected for the evaluation of CD19+, CD4+, CD3+, and CD8+ cell counts. These cells are present on white blood cells and are used as markers to associate cells with immune functions.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Ratio of CD 4+/CD8+
Blood samples of participants were collected for the evaluation of CD4+ and CD8+ cell counts and the ratio was calculated.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Rheumatoid Factor (RA Factor) >13 International Units Per Milliliter
Blood samples of participants were collected for the evaulation of RA factor. RA factor is an antibody found in the blood of participants with rheumatoid arthritis and is used for the diagnosis of rheumatoid arthritis.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Anti-cyclic Citrullinated Peptide Antibody (CCP) >6.9 International Units Per Liter
Blood samples of participants were collected for the evaluation of Anti-CCP. Anti-CCP plays an important role in immune response and helps assess the disease condition.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With B-Lymphocyte Stimulator (BLyS) >2.49 Micrograms Per Liter
Blood samples of participants were collected for the evaluation of BLyS. BLyS is a potent co-stimulator of B lymphocytes, and elevated levels of BLyS are observed in automimmune diseases. It regulates the immunnoglobin (antibody produced by B cells that is used by the immune system to indentify bacteria and viruses in the body) secretion of normal B cells (type of cells in the blood).
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Interleukin 6 (IL-6) >11.9 Picograms Per Milliliter
Blood samples of participants were collected for the evaluation of IL-6. IL-6 plays an important role in immune response and helps assess the disease condition.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid
Blood samples of participants were collected for the evaluation of uric acid and electrolytes (sodium, potassium, chloride, and calcium), as increased levels may reflect B-cell lysis due to treatment with ofatumumab.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Total Protein (TP) and Albumin
Blood samples of participants were collected to evaluate TP and albumin. TP can vary depending on auto-immune diseases, and TP and albumin can vary depending on debilitating diseases.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Total Bilirubin (TB) and Creatinine
Blood samples of participants were collected to evaluatate TB and creatinine levles. TB evlauation is performed to assess the condition of the liver, and possible hemolytic anemia, and the creatinine evaulation is performed to assess the renal condition (condition of the kidneys).
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Alanine Aminotranferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT)
Blood samples of participants were collected for the evaluation of ALT, AST, AP, and GGT. AST, ALT, AP, and GGT are evaluated to assess the condition of the liver.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Blood Urea Nitrogen (BUN)
The blood samples of participants were collected to assess the amount of nitrogen (in the form of urea) in the blood. BUN is evaluated to asssess the renal function of the participants.
Measured: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
The blood pressure (BP) of the participants was measured before infusion (infu) (BI) and post the first (A) and second (B) infusions (PI) during all 7 treatment courses.Timing for taking BP readings: SBP (BP when the heart is contracting): TC1, 2, 3 (infu A) more than 2 hours PI; TC1, 2 ,3 (infu B) 2 hours PI; TC4, 5, 6, 7 (infu A) 2 hours PI; TC4, 7 (infu B) 2 hours PI; TC5, 6 (infu B) 1 hour PI. For DBP (BP when the heart is resting between beats): TC1, 3 (infu A) more than 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC1, 2, 3, 4, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.
Measured: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
Assessment of Heart Rate (HR)
The HR of the participants was measured to assess the condition of the heart.HR was measured BI and post the first (A) and second (B) infusins during all 7 treatment courses.Timing for measuring HR: TC1, 3 (infu A) more than 2 hours PI; TC1, 2 ,3, 4, 7 (infu B) 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.
Measured: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
Assessment of Body Temperature (BT)
The BT of the participants was measured BI and post the first (A) and second (B) infusions (PI) of each cycle to assess the effect of ofatumumab on the BT.The BT of the participants was measured before BI and PI A and B during all 7 treatment courses.Timing for taking BT reading: TC1, 3 (infu A) more than 2 hours PI; TC1, 2 ,3, 4, 7 (infu B) 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.
Measured: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK)
Blood samples of participants were collected to assess LDH and CPK. Both tests are performed to evaluate the injury and damage to the body tissue, potentially from B-cell lysis.
Measured: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Normal and Abnormal Electrocardiogram Readings
Electrocardiograms of the participants were taken. The abnormal clinically significant (CS) and not clinically significant (NCS) reading, as determined by the Investigator, were recorded.
Measured: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2008 (estimated)
- Study start1 Jan 2008
- Primary completion25 May 2011
- Study completion19 Mar 2013
Why it stopped: The clinical development of intravenously administered ofatumumab in RA will no longer be pursued, so this study was prematurely terminated by the Sponsor.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00655824
- Sponsor's protocol ID
- 111752
- Other IDs
- GEN413
- Status last verified
- Oct 2017
- First submitted
- 4 Apr 2008
- Last updated
- 5 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, International, Multi-center, Phase II, Extension Trial Investigating Long-term Efficacy and Safety of Repeated Treatment Courses of Ofatumumab, a Fully Human Monoclonal Anti-CD20 Antibody, in Adult Patients With Active Rheumatoid Arthritis Who Previously Received Ofatumumab or Placebo
- ClinicalTrials.gov ID
- NCT00655824
- Acronym / sponsor ID
- 111752
- Conditions
- Arthritis, Rheumatoid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The clinical development of intravenously administered ofatumumab in RA will no longer be pursued, so this study was prematurely terminated by the Sponsor.
- Enrolment
- 124 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 1 Jan 2008
- Primary completion
- 25 May 2011 (actual)
- Study completion
- 19 Mar 2013 (actual)
- First posted
- 10 Apr 2008 (estimated)
- Results
- Posted 18 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A 3-year open-label trial for patients who previously participated in Trial Hx-CD20-403 and who fulfill the eligibility criteria for this trial (GEN413) . Th e primary purpose of the trial is to evaluate the long-term effectiveness of repeated courses ( a maximum of 9 treatment courses) of ofatumumab in RA patients who previously received ofatumumab or placebo in Trial Hx-CD20-403.
Detailed description
All patients who fulfill the eligibility criteria for this trial , will initiate at least one treatment course of ofatumumab, and depending of subsequent worsening in disease activity will be eligible to received further treatment through the 156 week treatment period: a maximum of a further 8 treatment courses will be given at individualized time intervals . The interval between each treatment course will be at least 16 weeks with the last treatment course given no later than week 130 after baseline (Visit 2A).
After each treatment course the patients will attend their next trial visit 8 weeks after Infusion 1, followed by trial visits every 4 weeks up to Week 24, and subsequently every 8 weeks until the next treatment course.
After completing the Treatment Period or after withdrawing from the Treatment Period prematurely patients will be followed every 12 weeks (Follow-up Period) until CD19+ cells \&/or IgG levels have returned to baseline or normal levels.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ofatumumab | Experimental | Drug: ofatumumab1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Previously received ofatumumab or placebo in Trial Hx-CD20-403.
- Patients on methotrexate therapy (7.5 - 25 mg/week, p.o., i.m., and/or s.c.).
- Oral corticosteroids therapy (≤ 10 mg/day prednisolone or equivalent).
- Active disease at the time of screening as defined by:
Key exclusion criteria (13 listed)
- Use of DMARDs other than methotrexate or exposure to other cell depleting therapy, including investigational compounds < 6 months prior to Visit 2 A.
- Patients who have received treatment with any non-marketed drug substance within 4 weeks prior to Visit 1 (screening).
- Breast feeding women or women with a positive pregnancy test at Visit 1 (screening).
- Received anti-cancer therapy, corticosteroids (intra-articular, i.m., or i.v.), or live/attenuated vaccinations, or exposure to cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents < 5 years prior to screening.
- Past or current malignancy, except for Cervical carcinoma Stage 1B or less, Non-invasive basal cell and squamous cell skin carcinoma, Malignant melanoma with a complete response of a duration of > 10 years, or other cancer diagnoses with a complete response of a duration of > 5 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ofatumumab1000 mL dilution of 35mls ofatumumab in sterile, pyrogen free, 0.9% NaCl | Drug | Ofatumumab |
Primary outcome
Time to Treatment Withdrawal
Time frame: From Baseline up to 144 weeks
Time to treatment withdrawal was defined as the time from the first infusion of ofatumumab until the date of treatment withdrawal. The sponsor discontinued the intravenous route of administration development program for rheumatoid arthritis (RA), and this study was terminated early; hence, this primary endpoint was not evaluated.
30 secondary outcomes
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour)
Time frame: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP)
Time frame: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Time to Re-treatment in Each Treatment Course
Time frame: Week 16 to Week 104 of each treatment course (up to 125 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Ofatumumab Serum Concentration
Time frame: Before infusion and at the end of infusion for each Treatment Course (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next TC; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial vi
Number of Participants Achieving American College of Rheumatology (ACR)20
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants Achieving ACR50
Time frame: Baseline of each TCand 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants Achieving ACR70
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With the Indicated European League Against Rheumatism (EULAR) Response
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants in the Indicated Categories of the Health Assessment Questionnaire (HAQ)
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With the Indicated Global Disease Assessment Using the VAS
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With the Indicated Pain Score
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With HAHA Response
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Whole Blood Transcriptional Profiles
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Percentage of Cluster of Differentiation (CD)19+, 4+, 3+, and 8+ B-cell Subsets in the Blood
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
CD19+, CD4+, CD3+, and CD8+ Cell Counts, Measured in mm^3
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Ratio of CD 4+/CD8+
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Rheumatoid Factor (RA Factor) >13 International Units Per Milliliter
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Anti-cyclic Citrullinated Peptide Antibody (CCP) >6.9 International Units Per Liter
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With B-Lymphocyte Stimulator (BLyS) >2.49 Micrograms Per Liter
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Interleukin 6 (IL-6) >11.9 Picograms Per Milliliter
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Sodium, Potassium, Chloride, Bicarbonate, Calcium, and Uric Acid
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Total Protein (TP) and Albumin
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Total Bilirubin (TB) and Creatinine
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Alanine Aminotranferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (AP), and Gamma Glutamyl-transferase (GGT)
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Blood Urea Nitrogen (BUN)
Time frame: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Time frame: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
Assessment of Heart Rate (HR)
Time frame: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
Assessment of Body Temperature (BT)
Time frame: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK)
Time frame: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Number of Participants With Normal and Abnormal Electrocardiogram Readings
Time frame: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ofatumumab in people with Arthritis, Rheumatoid, run by GlaxoSmithKline at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Denmark, Hungary, Poland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Treatment Withdrawal (time frame: From Baseline up to 144 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2017.