Systemic Lupus ErythematosusPhase 1NCT00046774
Monoclonal Antibody Treatment for Systemic Lupus Erythematosus
A Phase 1 study testing MRA 003 US in people with Systemic Lupus Erythematosus, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
Trial summary
This study will examine the safety and effects of the monoclonal antibody MRA in patients with systemic lupus erythematosus (SLE). Antibodies normally fight invading organisms. In autoimmune diseases, such as lupus, however, antibodies attack the body s own tissues. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- MRA 003 US
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2002to 7 Sep 2017
- Phase
- Phase 1
- 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
None listed.
Who cannot join
- Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test at screening.
- Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control during and for a period of three months after the completion of the study
- Any therapy with human or murine antibodies or any experimental therapy within 3 months
- Therapy with cyclophosphamide; pulse methylprednisolone or IV Ig within 4 weeks; or azathioprine, mycophenolate mofetil, cyclosporine or methotrexate within 2 weeks of first study treatment
- Initiation or a change in the dose of an ACE-inhibitor within 2 weeks of first study treatment
- Allergy to murine or human antibodies
Show all 21Show fewer
- History of anaphylaxis
- Serum creatinine greater than 3.0 mg/dL
- Active severe CNS lupus (encephalopathy, cerebrovascular accident, transverse myelitis, severe depression, psychosis)
- Previous history of ischemic heart disease or evidence of ischemic heart disease on ECG
- Congestive heart failure or cardiomyopathy
- History of thrombosis or recurrent 2nd trimester abortions (3 or more) and elevated levels of anti-cardiolipin antibodies or lupus anticoagulant unless the patient is on anticoagulation
- History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix within the last 3 years
- Active infection that requires the use of intravenous antibiotics and does not resolve within 1 week of Day 1
- Any active viral infection that does not resolve within 10 days prior to Day 1
- History of reactivation on EB viral infection or greater than 1,000 EBV genome equivalent/10(6) cells in PBMC preparations
- Active hepatitis B, hepatitis C or HIV infection
- WBC less than 3500/microL or ANC less than 3000/microL or Hgb less than 8.0 g/dL or platelets less than 50,000/microL or absolute lymphocyte count less than or equal to 500/microL.
- ALT and/or AST greater than 2 times the upper limit of normal (ULN) or alkaline phosphatase greater than 1.5 times the ULN
- Significant concurrent medical condition that, in the opinion of the principal investigator, could affect the patient's ability to tolerate or complete the study
- Live vaccines within 4 weeks of first infusion
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I, Open-Labeled, Dose-Ascending Clinical Trial of Immunotherapy of MRA, A Humanized Anti-IL 6 Receptor Monoclonal Antibody, In Patients With Systemic Lupus Erythematosus
This study will examine the safety and effects of the monoclonal antibody MRA in patients with systemic lupus erythematosus (SLE). Antibodies normally fight invading organisms. In autoimmune diseases, such as lupus, however, antibodies attack the body s own tissues. MRA is an antibody manufactured in the laboratory that blocks the action of interleukin-6 (IL-6), a substance that increases antibody production and is involved in inflammation that may cause organ damage in SLE.
Patients 18 years of age and older with moderately active systemic lupus erythematosus may be eligible for this 6-month study. Candidates will be screened with blood and urine tests, chest X-ray, electrocardiogram (EKG), and screening tests for certain cancers.
Read more
Participants will receive a total of up to seven infusions of MRA given every 2 weeks in the clinic. The MRA is infused over a period of about 1 hour through a catheter (thin plastic tube) inserted into an arm vein. Patients will be observed for 1 to 2 hours after each infusion for drug side effects. For the first and last infusions, patients will return to the clinic for blood tests 24 to 48 hours after the infusion. Additional tests may be done if medically indicated.
Three different doses of MRA will be used in three groups of patients. The first group (4 patients) will receive the lowest dose. If this dose is well tolerated, a second group (6 patients) will receive a higher dose. If this dose is also well tolerated, a third group (6 patients) will receive the highest study dose.
Patients will be evaluated at various intervals for up to 3 months after the last dose of MRA. The follow-up visits will include a review of the patient s medical history, a physical examination, blood and urine tests, and an EKG.
Read the detailed description
Interleukin-6 (IL-6) levels are elevated in both human and murine systemic lupus erythematosus (SLE). Blocking the action of IL-6 ameliorates disease activity in murine models of SLE. MRA is a humanized monoclonal antibody against the human IL-6 receptor. Data from clinical trials in patients with rheumatoid arthritis suggest that MRA may be a safe agent to block the effect of IL-6 and therefore may be used to evaluate the effects of IL-6 blockade in patients with SLE. In this open label, dose-escalating, Phase I study, up to 27 subjects with moderately active SLE may be enrolled. Subjects will be treated with bi-weekly infusions of one of three doses (2mg/kg, 4 mg/kg or 8 mg/kg) of MRA for 12 weeks and followed for 8 weeks after the last dose. Patients with or without lupus nephritis may be enrolled if they do not require immediate immunosuppressive therapy other than prednisone at doses of less than or equal to 0.3 mg/kg/day. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of MRA on SLE, clinical and laboratory evaluations and surrogate markers of inflammation and disease activity, such as autoantibody production and lymphocyte subsets, will be compared before and after the treatment. Patients who either do not tolerate the drug or those who have a clinically significant increase in their disease activity that does not respond to moderate doses of corticosteroids will be withdrawn from the protocol.
If this regimen is shown to be well tolerated, studies of efficacy will be planned. This agent is expected to be devoid of the most common toxicities of therapies commonly used in the treatment of SLE, such as myelosuppression, amenorrhea and osteoporosis.
This study will provide important preliminary information about the safety and possible effect of IL-6 blockade in SLE patients, an intervention that has been successful in animal models but has not yet been studied in humans.
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- MRA 003 US
- Keywords
- Safety, Nephritis, Biologic Therapy, Lymphocytes, Response, Lupus, Systemic Lupus Erythematosus, SLE
- Medical subject headings
- Lupus Erythematosus, Systemic, Nephritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRA 003 USDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety/tolerance of MRA in pts w/SLE
Measured: Wks 0,2,6,12,14,20
Secondary outcomes (1)
Clinical Pharmacokinetics of MRA
Measured: Wks 0,2,6,12,14,20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2002 (estimated)
- Study start2 Sep 2002
- Primary completion1 Jan 2007
- Study completion7 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sarfaraz A Hasni, M.D., Principal investigator, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00046774
- Sponsor's protocol ID
- 020272
- Other IDs
- 02-AR-0272
- Status last verified
- 7 Sep 2017
- First submitted
- 2 Oct 2002
- Last updated
- 12 Dec 2019
- Results posted
- No
Publications
Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bluethmann H, Kohler G. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994 Mar 24;368(6469):339-42. doi: 10.1038/368339a0.
PubMed 8127368Bromander AK, Ekman L, Kopf M, Nedrud JG, Lycke NY. IL-6-deficient mice exhibit normal mucosal IgA responses to local immunizations and Helicobacter felis infection. J Immunol. 1996 Jun 1;156(11):4290-7.
PubMed 8666800Ramsay AJ, Husband AJ, Ramshaw IA, Bao S, Matthaei KI, Koehler G, Kopf M. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science. 1994 Apr 22;264(5158):561-3. doi: 10.1126/science.8160012.
PubMed 8160012Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, Fleisher T, Balow JE, Lipsky PE. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010 Feb;62(2):542-52. doi: 10.1002/art.27221.
PubMed 20112381
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Open-Labeled, Dose-Ascending Clinical Trial of Immunotherapy of MRA, A Humanized Anti-IL 6 Receptor Monoclonal Antibody, In Patients With Systemic Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT00046774
- Acronym / sponsor ID
- 020272
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Safety, Nephritis, Biologic Therapy, Lymphocytes, Response, Lupus, Systemic Lupus Erythematosus, SLE
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)US National Institutes of Health
- Study start
- 2 Sep 2002
- Primary completion
- 1 Jan 2007 (actual)
- Study completion
- 7 Sep 2017 (actual)
- First posted
- 3 Oct 2002 (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.
This study will examine the safety and effects of the monoclonal antibody MRA in patients with systemic lupus erythematosus (SLE). Antibodies normally fight invading organisms. In autoimmune diseases, such as lupus, however, antibodies attack the body s own tissues. MRA is an antibody manufactured in the laboratory that blocks the action of interleukin-6 (IL-6), a substance that increases antibody production and is involved in inflammation that may cause organ damage in SLE.
Patients 18 years of age and older with moderately active systemic lupus erythematosus may be eligible for this 6-month study. Candidates will be screened with blood and urine tests, chest X-ray, electrocardiogram (EKG), and screening tests for certain cancers.
Participants will receive a total of up to seven infusions of MRA given every 2 weeks in the clinic. The MRA is infused over a period of about 1 hour through a catheter (thin plastic tube) inserted into an arm vein. Patients will be observed for 1 to 2 hours after each infusion for drug side effects. For the first and last infusions, patients will return to the clinic for blood tests 24 to 48 hours after the infusion. Additional tests may be done if medically indicated.
Three different doses of MRA will be used in three groups of patients. The first group (4 patients) will receive the lowest dose. If this dose is well tolerated, a second group (6 patients) will receive a higher dose. If this dose is also well tolerated, a third group (6 patients) will receive the highest study dose.
Patients will be evaluated at various intervals for up to 3 months after the last dose of MRA. The follow-up visits will include a review of the patient s medical history, a physical examination, blood and urine tests, and an EKG.
Detailed description
Interleukin-6 (IL-6) levels are elevated in both human and murine systemic lupus erythematosus (SLE). Blocking the action of IL-6 ameliorates disease activity in murine models of SLE. MRA is a humanized monoclonal antibody against the human IL-6 receptor. Data from clinical trials in patients with rheumatoid arthritis suggest that MRA may be a safe agent to block the effect of IL-6 and therefore may be used to evaluate the effects of IL-6 blockade in patients with SLE. In this open label, dose-escalating, Phase I study, up to 27 subjects with moderately active SLE may be enrolled. Subjects will be treated with bi-weekly infusions of one of three doses (2mg/kg, 4 mg/kg or 8 mg/kg) of MRA for 12 weeks and followed for 8 weeks after the last dose. Patients with or without lupus nephritis may be enrolled if they do not require immediate immunosuppressive therapy other than prednisone at doses of less than or equal to 0.3 mg/kg/day. Safety will be evaluated using standard clinical and laboratory parameters. To assess the potential effect of MRA on SLE, clinical and laboratory evaluations and surrogate markers of inflammation and disease activity, such as autoantibody production and lymphocyte subsets, will be compared before and after the treatment. Patients who either do not tolerate the drug or those who have a clinically significant increase in their disease activity that does not respond to moderate doses of corticosteroids will be withdrawn from the protocol.
If this regimen is shown to be well tolerated, studies of efficacy will be planned. This agent is expected to be devoid of the most common toxicities of therapies commonly used in the treatment of SLE, such as myelosuppression, amenorrhea and osteoporosis.
This study will provide important preliminary information about the safety and possible effect of IL-6 blockade in SLE patients, an intervention that has been successful in animal models but has not yet been studied in humans.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (21 listed)
- Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test at screening.
- Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control during and for a period of three months after the completion of the study
- Any therapy with human or murine antibodies or any experimental therapy within 3 months
- Therapy with cyclophosphamide; pulse methylprednisolone or IV Ig within 4 weeks; or azathioprine, mycophenolate mofetil, cyclosporine or methotrexate within 2 weeks of first study treatment
- Initiation or a change in the dose of an ACE-inhibitor within 2 weeks of first study treatment
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 |
|---|---|---|
| MRA 003 US | Drug | – |
Primary outcome
Safety/tolerance of MRA in pts w/SLE
Time frame: Wks 0,2,6,12,14,20
1 secondary outcome
Clinical Pharmacokinetics of MRA
Time frame: Wks 0,2,6,12,14,20
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 Dec 2019.
- Background: PubMed 8127368Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bluethmann H, Kohler G. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994 Mar 24;368(6469):339-42. doi: 10.1038/368339a0.
- Background: PubMed 8666800Bromander AK, Ekman L, Kopf M, Nedrud JG, Lycke NY. IL-6-deficient mice exhibit normal mucosal IgA responses to local immunizations and Helicobacter felis infection. J Immunol. 1996 Jun 1;156(11):4290-7.
- Background: PubMed 8160012Ramsay AJ, Husband AJ, Ramshaw IA, Bao S, Matthaei KI, Koehler G, Kopf M. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science. 1994 Apr 22;264(5158):561-3. doi: 10.1126/science.8160012.
- Derived from this study: PubMed 20112381Illei GG, Shirota Y, Yarboro CH, Daruwalla J, Tackey E, Takada K, Fleisher T, Balow JE, Lipsky PE. Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study. Arthritis Rheum. 2010 Feb;62(2):542-52. doi: 10.1002/art.27221.
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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.
Sarfaraz A Hasni, M.D. principal investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MRA 003 US in people with Systemic Lupus Erythematosus, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
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 0 inclusion and 21 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 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Safety/tolerance of MRA in pts w/SLE (time frame: Wks 0,2,6,12,14,20). 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 NCT00046774, which also lists 4 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 Dec 2019.