Arthritis, RheumatoidPhase 2NCT00291928
HuMax-CD20 in Active Rheumatoid Arthritis, Phase I/II
A Phase 2 study testing Part A and Part B in people with Arthritis, Rheumatoid, run by GlaxoSmithKline.
Trial summary
The purpose of this trial is primarily to investigate the safety profile of HuMax-CD20 in patients with active RA. Furthermore, the trial is designed to identify the dose levels to be used in future trials (based on evaluations of safety, pharmacokinetics and ACR and DAS responses). 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?
- Part A and Part B
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 201 participants
- Where
- No sites listed yet
- Study dates
- Feb 2005to Sep 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Age ≥ 18 years
- Active rheumatoid arthritis according to the American College of Rheumatology of at least six months duration with six or more swollen and six or more tender joints (of 28 joints) and Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/h and/or C-Reactive Protein (CRP) ≥ 10 mg/L (1 mg/dL).
- Treatment failure to one or more DMARDs.
- Treatment with methotrexate (7.5-25 mg/wk) for at least 12 weeks and at a stable dose for at least 4 weeks prior to planned start of trial treatment.
Who cannot join
- Use of DMARDs other than methotrexate.
- Current or previous (within four weeks of screening) participation in any other clinical trial.
- Previous exposure to other biological products within 4 weeks prior to planned start of trial treatment, and/or exposure to anti-CD20 antibodies within two years before screening for this trial.
- Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial.
- Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy.
- Past or current malignancy, except for resected 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.
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- Chronic or current infectious disease including known or suspected positive serology for HIV, hepatitis B, or hepatitis C.
- Clinically significant cardiac disease, or history of significant cerebrovascular disease.
- Significant concurrent, uncontrolled medical condition including, but not limited to: renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
- Breast feeding women, women with a positive pregnancy test at screening, or women of childbearing potential not willing to use adequate contraception during the trial.
About this study
Official title: A Double-blind, Randomized, Placebo Controlled, Dose Escalation, Multi-centerphase I/II Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20antibody, in Patients With Active Rheumatoid Arthritis Who Have Previously Failedone or More Disease Modifying Anti-rheumatic Drugs
The purpose of this trial is primarily to investigate the safety profile of HuMax-CD20 in patients with active RA. Furthermore, the trial is designed to identify the dose levels to be used in future trials (based on evaluations of safety, pharmacokinetics and ACR and DAS responses).
Read the detailed description
This trial consists of a double-blind, placebo controlled, dose escalation part with randomization to trial treatment within each of three sequential cohorts (Part A), and a parallel group part with randomization into one of four treatment arms (Part B). Patients in Parts A and B will receive two infusions of either HuMax-CD20 (300 mg, 700 mg, or 1000 mg) or placebo and will be followed for safety, efficacy, and pharmacokinetic measurements for 24 weeks. Hereafter patients will be followed every 12 weeks until B-cells (CD19+ cells) have returned to baseline levels. For patients in Part B, the follow-up visits at 36 and 48 weeks after initial trial treatment (Follow-up Visits 1 and 2) will include additional measurements of safety and efficacy.
- Conditions
- Arthritis, Rheumatoid
- Being tested
- Part A, Part B
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Part ADrug
Part A Cohort 1: HuMax-CD20 300 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 2: HuMax-CD20 700 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 3: HuMax-CD20 1000 mg at Days 0 and 14 or Placebo at Days 0 and 14
Part BDrug
Part B Group 1: HuMax-CD20 300 mg at Days 0 and 14 Group 2: HuMax-CD20 700 mg at Days 0 and 14 Group 3: HuMax-CD20 1000 mg at Days 0 and 14 Group 4: Placebo at Days 0 and 14
| Study group | Role | What they receive |
|---|---|---|
| Dose ranging | Placebo comparator | A double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A), Receives: Drug: Part A |
| Parallel Arm RCT | Placebo comparator | a parallel group part with randomization into one of 4 treatment arms (Part B). Receives: Drug: Part B |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
Measured: 24 weeks
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment
Measured: 24 weeks
Secondary outcomes (5)
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion
Measured: 24 weeks
To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis
Measured: 24 weeks
To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20
Measured: 24 weeks
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 36 & 48 weeks after initiation of treatment
Measured: 48 weeks
To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2006 (estimated)
- Study startFeb 2005
- Primary completionSep 2007
- Study completionSep 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 201 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
- NCT00291928
- Sponsor's protocol ID
- 112657
- Other IDs
- HX-CD20-403
- Status last verified
- Nov 2012
- First submitted
- 14 Feb 2006
- Last updated
- 12 Nov 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
Struemper H, Sale M, Patel BR, Ostergaard M, Osterborg A, Wierda WG, Hagenbeek A, Coiffier B, Jewell RC. Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis. J Clin Pharmacol. 2014 Jul;54(7):818-27. doi: 10.1002/jcph.268. Epub 2014 Jan 28.
PubMed 24443277Ostergaard M, Baslund B, Rigby W, Rojkovich B, Jorgensen C, Dawes PT, Wiell C, Wallace DJ, Tamer SC, Kastberg H, Petersen J, Sierakowski S. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum. 2010 Aug;62(8):2227-38. doi: 10.1002/art.27524.
PubMed 20506254
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Placebo Controlled, Dose Escalation, Multi-centerphase I/II Trial of HuMax-CD20, a Fully Human Monoclonal Anti-CD20antibody, in Patients With Active Rheumatoid Arthritis Who Have Previously Failedone or More Disease Modifying Anti-rheumatic Drugs
- ClinicalTrials.gov ID
- NCT00291928
- Acronym / sponsor ID
- 112657
- Conditions
- Arthritis, Rheumatoid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 201 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Feb 2005
- Primary completion
- Sep 2007 (actual)
- Study completion
- Sep 2007 (actual)
- First posted
- 15 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is primarily to investigate the safety profile of HuMax-CD20 in patients with active RA. Furthermore, the trial is designed to identify the dose levels to be used in future trials (based on evaluations of safety, pharmacokinetics and ACR and DAS responses).
Detailed description
This trial consists of a double-blind, placebo controlled, dose escalation part with randomization to trial treatment within each of three sequential cohorts (Part A), and a parallel group part with randomization into one of four treatment arms (Part B). Patients in Parts A and B will receive two infusions of either HuMax-CD20 (300 mg, 700 mg, or 1000 mg) or placebo and will be followed for safety, efficacy, and pharmacokinetic measurements for 24 weeks. Hereafter patients will be followed every 12 weeks until B-cells (CD19+ cells) have returned to baseline levels. For patients in Part B, the follow-up visits at 36 and 48 weeks after initial trial treatment (Follow-up Visits 1 and 2) will include additional measurements of safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose ranging | Placebo comparator | Drug: Part AA double-blind, placebo controlled, dose escalation part randomized within each of 3 sequential cohorts (Part A), |
| Parallel Arm RCT | Placebo comparator | Drug: Part Ba parallel group part with randomization into one of 4 treatment arms (Part B). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 18 years
- Active rheumatoid arthritis according to the American College of Rheumatology of at least six months duration with six or more swollen and six or more tender joints (of 28 joints) and Erythrocyte Sedimentation Rate (ESR) ≥ 22 mm/h and/or C-Reactive Protein (CRP) ≥ 10 mg/L (1 mg/dL).
- Treatment failure to one or more DMARDs.
- Treatment with methotrexate (7.5-25 mg/wk) for at least 12 weeks and at a stable dose for at least 4 weeks prior to planned start of trial treatment.
Key exclusion criteria (10 listed)
- Use of DMARDs other than methotrexate.
- Current or previous (within four weeks of screening) participation in any other clinical trial.
- Previous exposure to other biological products within 4 weeks prior to planned start of trial treatment, and/or exposure to anti-CD20 antibodies within two years before screening for this trial.
- Any use of cyclophosphamide, nitrogen mustard, chlorambucil or other alkylating agents within five years before screening for this trial.
- Active autoimmune disease (other than RA and RA-associated secondary diseases) requiring immunosuppressive therapy.
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 |
|---|---|---|
| Part APart A Cohort 1: HuMax-CD20 300 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 2: HuMax-CD20 700 mg at Days 0 and 14 or Placebo at Days 0 and 14 Cohort 3: HuMax-CD20 1000 mg at Days 0 and 14 or Placebo at Days 0 and 14 | Drug | Dose ranging |
| Part BPart B Group 1: HuMax-CD20 300 mg at Days 0 and 14 Group 2: HuMax-CD20 700 mg at Days 0 and 14 Group 3: HuMax-CD20 1000 mg at Days 0 and 14 Group 4: Placebo at Days 0 and 14 | Drug | Parallel Arm RCT |
Primary outcome
To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis
Time frame: 24 weeks
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 12 to 24 weeks after initiation of treatment
Time frame: 24 weeks
5 secondary outcomes
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis by measuring the degree and duration of B-cell depletion
Time frame: 24 weeks
To determine the pharmacokinetic profile of HuMax-CD20 in patients with active rheumatoid arthritis
Time frame: 24 weeks
To determine host immune response, Human Anti Human Antibodies (HAHA), against HuMax-CD20
Time frame: 24 weeks
To evaluate the efficacy of HuMax-CD20 in patients with active rheumatoid arthritis using the American College of Rheumatology (ACR) Response Assessment and Disease Activity Score (DAS) at 36 & 48 weeks after initiation of treatment
Time frame: 48 weeks
To evaluate if Fc-receptor polymorphism influences the safety and efficacy of HuMax-CD20 in patients with active rheumatoid arthritis
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2012.
- Derived from this study: PubMed 24443277Struemper H, Sale M, Patel BR, Ostergaard M, Osterborg A, Wierda WG, Hagenbeek A, Coiffier B, Jewell RC. Population pharmacokinetics of ofatumumab in patients with chronic lymphocytic leukemia, follicular lymphoma, and rheumatoid arthritis. J Clin Pharmacol. 2014 Jul;54(7):818-27. doi: 10.1002/jcph.268. Epub 2014 Jan 28.
- Derived from this study: PubMed 20506254Ostergaard M, Baslund B, Rigby W, Rojkovich B, Jorgensen C, Dawes PT, Wiell C, Wallace DJ, Tamer SC, Kastberg H, Petersen J, Sierakowski S. Ofatumumab, a human anti-CD20 monoclonal antibody, for treatment of rheumatoid arthritis with an inadequate response to one or more disease-modifying antirheumatic drugs: results of a randomized, double-blind, placebo-controlled, phase I/II study. Arthritis Rheum. 2010 Aug;62(8):2227-38. doi: 10.1002/art.27524.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Part A and Part B in people with Arthritis, Rheumatoid, run by GlaxoSmithKline.
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 4 inclusion and 10 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: finished, as of the sponsor's last update on 12 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To evaluate the safety of HuMax-CD20 in patients with active rheumatoid arthritis (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00291928, which also lists 2 linked publications.
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 12 Nov 2012.