Monoclonal Antibody Treatment for Systemic Lupus Erythematosus

NCT00046774 | Completed Phase 1

• 2 other identifiers: 02027202-AR-0272
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Systemic Lupus Erythematosus

Keywords

Safety; Nephritis; Biologic Therapy; Lymphocytes; Response; Lupus; Systemic Lupus Erythematosus; SLE

Outcome Measures

Primary Outcomes (1)

• Safety/tolerance of MRA in pts w/SLE

  Wks 0,2,6,12,14,20

Secondary Outcomes (1)

• Clinical Pharmacokinetics of MRA

  Wks 0,2,6,12,14,20

Interventions

MRA 003 US DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at entry at least 18 years
• Must give written informed consent prior to entry in the protocol
• Must fulfill at least 4 of the following criteria for SLE as defined by the American College of Rheumatology:
• Malar rash. Fixed Erythema, flat or raised, over the malar eminences.
• Discoid rash. Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur.
• Photosensitivity. Exposure to UV light causes rash.
• Oral Ulcers. Includes oral and nasopharyngeal, observed by physician.
• Arthritis. Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling or effusion.
• Serositis. Pleuritis or pericarditis documented by ECG or rub or evidence of pericardial effusion.
• Renal disorder. Proteinuria greater than 0.5 g/d or greater than 3+, or cellular casts.
• Neurologic disorder. Seizures without other cause or psychosis without other cause.
• Hematologic disorder. Hemolytic anemia or leukopenia (less than 4000/microL) or lymphopenia (less than 1500/microL) or thrombocytopenia (less than 100,000/microL) in the absence of offending drugs.
• Immunologic disorder. Anti-dsDNA, anti-Sm, and/or anti-phospholipid.
• Antinuclear antibodies. An abnormal titer of ANAs by immunofluorescence or an equivalent assay at any point in time in the absence of drugs known to induce ANAs.
• Moderately active lupus not requiring immediate immunosuppressive therapy other than oral prednisone less than or equal to 0.3 mg/kg/day (or its equivalent). Moderately active lupus is defined by either of these two (a and b) sets of criteria:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• 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.

  PMID: 8127368 BACKGROUND

• Bromander 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.

  PMID: 8666800 BACKGROUND

• Ramsay 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.

  PMID: 8160012 BACKGROUND

• Illei 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.

  PMID: 20112381 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Nephritis

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Sarfaraz A Hasni, M.D.

  National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2002
• First Posted: October 3, 2002
• Study Start: September 2, 2002
• Primary Completion: January 1, 2007
• Study Completion: September 7, 2017
• Last Updated: December 12, 2019

Record last verified: 2017-09-07

Locations

US (1)