Monoclonal Antibody Treatment for Systemic Lupus Erythematosus

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00046774
• Date of registration: 02/10/2002
• Prospective Registration: No
• Primary sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Public title: Monoclonal Antibody Treatment for Systemic Lupus Erythematosus
• Scientific 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
• Date of first enrolment: September 2, 2002
• Target sample size: 23
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00046774
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Sarfaraz A Hasni, M.D.
• Affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Key inclusion & exclusion criteria

- IINCLUSION CRITERIA:

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:

a. Chronic glomerulonephritis with inadequate response to at least 6 months of adequate
immunosuppressive therapy (with pulse methylprednisolone, cyclophosphamide, azathioprine,
cyclosporine, mycophenolate mofetil or high dose daily corticosteroids, MTX or IV Ig), and

i. less than 30% increase in creatinine compared to lowest level during treatment,

ii. proteinuria less than or equal to 1.5 times the baseline before treatment,

iii. less than or equal to 2+ cellular casts in the urinary sediment (on a scale of 0-4),
and

iv. Extra-renal disease activity does not exceed 10 on the non-renal components of the
SELENA-SLEDAI score.

b. Patients with moderately active extra-renal lupus defined as an extra-renal
SELENA-SLEDAI score in the range of 3 to 10, inclusive. The SELENA-SLEDAI score should have
been stable for at least two weeks prior to screening.

One or more of the following:

i) Serum dsDNA level greater than or equal to 30 IU

ii) IgG anticardiolipin antibody levels greater than or equal to 20 GPL

iii) CRP greater than 0.8 mg/dL

iv) ESR greater than 25 mm/hr for men; ESR greater than 42 mm/hr for women.

Stable doses of prednisone less than or equal to 0.3 mg/kg/day (or its equivalent) for at
least 2 weeks before the first treatment.

EXCLUSION CRITERIA:

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

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: MRA 003 US

Primary Outcome(s)

Safety/tolerance of MRA in pts w/SLE [Time Frame: Wks 0,2,6,12,14,20]

Secondary Outcome(s)

Clinical Pharmacokinetics of MRA [Time Frame: Wks 0,2,6,12,14,20]

Secondary ID(s)

02-AR-0272

020272

Source(s) of Monetary Support

Please refer to primary and secondary sponsors