Omalizumab for Lupus

NCT01716312 | Completed Phase 1 FDA Drug

• 2 other identifiers: 13000513-AR-0005
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Systemic Lupus Erthematosus; Sjogren's Syndrome

Keywords

Safety Of Omalizumab In Patients With SLE; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Safety of omalizumab in patients with SLE.

  The primary outcome is to evaluate the safety and tolerance of omalizumab in patients with SLE. This analysis will include rates ofadverse events (serious adverse events, Grade 3 and 4 toxicities not fulfilling the criteria for SAE, and nonserious adverse events).

  Outcome measure are assessed once the last participant completes the last visit.

Secondary Outcomes (1)

• Reduced free IgE autoantibody levels. Decreased basophil activation. Reduced IgG autoantibody levels. Pharmacodynamics. Clinical efficacy.

  Outcome measure are assessed once the last participant completes the last visit.

Study Arms (2)

1

PLACEBO COMPARATOR

Subjects who were randomized to the placebo arm originally will receive 600 mg omalizumab by subcutaneous injection

Drug: Omalizumab

2

ACTIVE COMPARATOR

Subjects in the omalizumab arm will receive 300 mg omalizumab by subcutaneous injection in a doubleblinded fashion

Drug: Omalizumab

Interventions

Omalizumab DRUG

For each subject, treatment with omalizumab will start with a loading dose of 600 mg followed by a maintenance dose of 300 mg every 4 weeks. The study drug will be administered as a subcutaneous injection. On Week 0 and Week 16 the medication or placebo will be administered to subjects via 4 subcutaneous injections; the remaining weeks 2 injections will be administered.Subjects will be given written directions on dealing with adverse reactions. They will also receive an Epi-Pen before discharge and instructions on how to use it.

1; 2

Eligibility Criteria

• Age: 18 Years - 100 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. 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:
• 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.

You may not qualify if:

• 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 \> 105 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.
• 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

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)

• 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. doi: 10.1038/nm.2159. Epub 2010 May 30.

  PMID: 20512127 BACKGROUND

• 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.

  PMID: 18472983 BACKGROUND

• 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. doi: 10.1159/000321824. Epub 2010 Oct 25.

  PMID: 20975283 BACKGROUND

• Hasni S, Gupta S, Davis M, Poncio E, Temesgen-Oyelakin Y, Joyal E, Fike A, Manna Z, Auh S, Shi Y, Chan D, Carlucci P, Biehl A, Dema B, Charles N, Balow JE, Waldman M, Siegel RM, Kaplan MJ, Rivera J. Safety and Tolerability of Omalizumab: A Randomized Clinical Trial of Humanized Anti-IgE Monoclonal Antibody in Systemic Lupus Erythematosus. Arthritis Rheumatol. 2019 Jul;71(7):1135-1140. doi: 10.1002/art.40828. Epub 2019 May 8.

  PMID: 30597768 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sjogren's Syndrome; Lupus Erythematosus, Systemic

Interventions

Omalizumab

Condition Hierarchy (Ancestors)

Arthritis, Rheumatoid; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Xerostomia; Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Dry Eye Syndromes; Lacrimal Apparatus Diseases; Eye Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Anti-Idiotypic; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Serum Globulins; Globulins

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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: October 29, 2012
• Study Start: January 8, 2014
• Primary Completion: August 24, 2017
• Study Completion: August 24, 2017
• Last Updated: April 20, 2022

Record last verified: 2022-04

Locations

US (1)