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Protocol Details

A Phase 1b, Randomized, Double-Blind, Placebo Controlled Study with an Open Label Extension to Evaluate the Safety and Tolerability of Omalizumab, A Humanized IgG1 Monoclonal Antibody in Patients with Lupus (STOP LUPUS)

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

13-AR-0005

Sponsoring Institute

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

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Systemic Lupus Erythematosus

Recruitment Keyword(s)

None

Condition(s)

Systemic Lupus Erthematosus;
Sjogren's Syndrome

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

Drug: Omalizumab
Drug: Placebo

Supporting Site

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Background:

- Systemic Lupus Erythematosus (SLE or lupus) is an autoimmune disease, which means the body's immune system mistakenly attacks healthy tissue resulting in inflammation and tissue damage. SLE can involve almost any organ and its symptoms can range in severity from mild to life-threatening; symptoms also vary from person to person. Current treatments for lupus are not effective for some people. Medications used to treat lupus can have serious side effects.

- Omalizumab is a drug that has been used to treat severe allergic asthma. It helps to prevent allergic reactions by reducing some antibodies in the blood. These antibodies are also present in some people with Lupus. Researchers want to see if omalizumab is a safe and effective treatment for people with Lupus.

Objectives:

- To test the safety of omalizumab for people with lupus.

Eligibility:

- Individuals at least 18 years of age who have moderately active Lupus even with standard treatments.

Design:

- Subject screening will take place at the NIH Clinical Center and will include a medical history, a physical exam, blood and urine laboratory tests, an assessment of Lupus disease activity. Some participants may require some additional testing. All eligible persons who are interested in enrolling will be asked to come back to the NIH within 2 weeks to begin the study.

- The study will be conducted in three phases, with a total of 15 study visits over 38 weeks. Two visits will be overnight hospital stays. The rest will be outpatient visits. During each visit the participants will be monitored by doing a physical exam, assessment of their lupus disease activity, review of any treatment related side effects, blood and urine testing.

- For the first phase, participants will have infusions (under their skin) of either omalizumab or a placebo. They will have an overnight hospital stay for the first infusion and then an outpatient safety monitor visit 2 weeks after. If subjects safety measures are good they will return in 2 weeks and receive the second dose. They will then get three more doses every 4 weeks which will be given during outpatient visits to the NIH.

- In the second phase, which begins at the 16th week of the study, all participants will receive omalizumab. This means that subjects who had been getting omalizumab will continue receiving it and subjects who had been receiving the placebo will now begin getting omalizumab. They will have an overnight hospital stay for this infusion and will return in 2 weeks for a safety monitor visit. If subjects safety measures are good they will return in 2 weeks and receive the next dose. They will then get three more doses every 4 weeks which will be given during outpatient visits to the NIH.

-The third phase will be a final series of visits which will take place at week 32 and week 36. During these visits subjects will have a physical exam which includes disease activity assessment, blood and urine tests. No medication will be given during these visits.

-All subjects will be given information, instruction and medications for possible allergic reactions to omalizumab.

-Throughout the study other tests and procedures will be performed as needed.

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Eligibility

INCLUSION CRITERIA:

Age at entry at least 18 years

Must give written informed consent prior to entry in the protocol. After preliminary screening visit under the Studies of the pathogenesis and natural history of systemic lupus erythematosus (SLE) protocol 94-AR-0066.

Must fulfill at least 4 of the criteria for SLE as defined by the American College of Rheumatology (Criteria published by EM Tan et al., Arthritis Rheum 25:1271, 1982, updated by MC Hochberg, Arthritis Rheum 40:1725, 1997).

Increased (> mean plus 2SD of healthy controls) autoantibody levels of any of the following IgE autoantibodies: anti-dsDNA, anti-Sm, anti-SSA.

Moderately active lupus defined by either of these (a or b) sets of criteria:

a) Chronic glomerulonephritis: Subjects who meet following conditions at 8 weeks after completion of adequate induction immunosuppressive therapy:

-Subjects with lupus nephritis not achieving complete renal response

defined as A) no active urinary sediment at the time of screening AND

B) Urinary protein to creatinine ratio of < 1 mg/mg or 24 hours urinary protein of less than 1 gm at the time of screening.

-Received at least 6 months of adequate induction immunosuppressive therapy (with pulse methylprednisolone, cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil or high dose daily corticosteroids),

AND all of the following as assessed at the time of screening:

- less than 30 percent increase in creatinine compared to lowest level during treatment with induction immunosuppressive therapy,

- proteinuria < 1.5 times before starting treatment with induction immunosuppressive therapy,

- < 2 plus cellular casts in the urinary sediment (on a scale of 0-4), and

- Extra-renal disease activity does not exceed 10 on the non-renal components of the SLEDAI 2K score.

(b)Patients with no active lupus nephritis and moderately active extra-renal lupus defined as a SLEDAI 2K score in the range of 4-14, inclusive.

Medications allowed at entry:

-Prednisone less than or equal to 20 mg/day

-Hydroxychloroquine up to 400 mg or 6.5 mg/kg/day (if > 400 mg)

-Methotrexate up to 25 mg once a week

-Azathioprine up to 2 mg/kg/day

-Mycophenolate mofetil up to 3 grams/day

-Cyclosporine up to 5 mg/kg/day

EXCLUSION CRITERIA:

Subjects will be excluded from the study if they meet any of the following 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 two forms of birth control during and for a period of 3 months after the completion of the study. Acceptable forms of birth control include abstinence, barrier methods, implantable intrauterine devices and oral, transdermal patch or injectable contraceptives.

Weight > 100 kg

Total IgE level > 700 IU/mL

Active SLE requiring aggressive immunosuppressive therapy (ie CNS vasculitis, proliferative lupus nephritis requiring induction therapy, etc)

History of stroke, MI

Use of rituximab within 6 months or any other biologic within 5 half-life of the drug at the time the first administration of study medication.

Peripheral blood CD19 plus B cell count < 5/microL

Significant impairment of major organ function (lung, heart, liver, kidney)

Therapy with cyclophosphamide, pulse methylprednisolone or IVIG within 8 weeks at the time of first administration of study medication.

Initiation or a change in the dose of an ACE-inhibitor or ARB within 2 weeks of first study treatment.

Allergy to murine or human antibodies

History of anaphylaxis

Bronchial asthma treated within 12 months

Serum creatinine > 2.0 mg/dL

Previous history of ischemic heart disease or evidence of ischemic heart disease on ECG.

Congestive heart failure (New York Heart Association Class III and IV) or cardiomyopathy as per the assessment of clinician performing history and physical examination and to be confirmed by echocardiogram when clinically indicated.

History of thrombosis or recurrent 2nd trimester spontaneous abortions (3 or more) and elevated levels of anti-cardiolipin antibodies or lupus anticoagulant

History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix.

Active infection that requires the use of intravenous antibiotics and has not resolved at least 2 weeks prior to the administration of the first dose of study medication.

Active hepatitis B, hepatitis C or HIV infection

WBC < 2,500/microL or ANC < 1,500/microL or Hgb < 8.0 g/dL or platelets < 70,000/microL or absolute lymphocyte count < 500/microL.

Alkaline phosphatase, ALT and/or AST > 2.0 times upper limit of normal (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 injection.

Known or suspected Helminthic infection/infestation.

History of menorrhagia, GI Bleed or other clinically significant bleeding.

Subjects currently on anticoagulants or anti-platelet agents. Any subject who was on these agents in the past within the biologic half-life of these agents will also be excluded. Daily baby aspirin (81 mg) therapy for the prevention of cardiovascular disease (CVD) will be allowed.


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Citations:

Charles N, Hardwick D, Daugas E, Illei GG, Rivera J. Basophils and the T helper 2 environment can promote the development of lupus nephritis. Nat Med. 2010 Jun;16(6):701-7. Epub 2010 May 30.

D'Amato G, Salzillo A, Piccolo A, D'Amato M, Liccardi G. A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma. Ther Clin Risk Manag. 2007 Aug;3(4):613-9.

Gernez Y, Tirouvanziam R, Yu G, Ghosn EE, Reshamwala N, Nguyen T, Tsai M, Galli SJ, Herzenberg LA, Herzenberg LA, Nadeau KC. Basophil CD203c levels are increased at baseline and can be used to monitor omalizumab treatment in subjects with nut allergy. Int Arch Allergy Immunol. 2011;154(4):318-27. Epub 2010 Oct 25.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Sarfaraz A. Hasni, M.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
BG 10-CRC RM 5-2340
10 CENTER DR
BETHESDA MD 20814
(301) 451-1599
hasnisa@mail.nih.gov

Elizabeth Joyal, R.N.
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institutes of Health
Building 10
Room 3C709
10 Center Drive
Bethesda, Maryland 20892
(301) 435-4489
ejoyal@mail.cc.nih.gov

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

prpl@mail.cc.nih.gov

Clinical Trials Number:

NCT01716312

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