A Study of AMG 557 in Adults With Systemic Lupus Erythematosus

NCT ID: NCT00774943

Last Updated: 2013-04-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-31
• Study Completion Date: 2012-05-31

Brief Summary

This is a Phase 1, randomized, placebo-controlled, double-blind, dose-escalation study of repeat SC doses of AMG 557 in adults with Systemic Lupus Erythematosus.

Conditions

Systemic Lupus Erythematosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AMG 557

Group Type: ACTIVE_COMPARATOR

AMG 557

Intervention Type: DRUG

A total of 4 cohorts will be administered multiple doses of drug or placebo subcutaneously. Dose escalation will take place by cohort.

Placebo

Group Type: PLACEBO_COMPARATOR

AMG 557

Intervention Type: DRUG

A total of 4 cohorts will be administered multiple doses of drug or placebo subcutaneously. Dose escalation will take place by cohort.

Interventions

AMG 557

A total of 4 cohorts will be administered multiple doses of drug or placebo subcutaneously. Dose escalation will take place by cohort.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Before any study-specific procedure, the appropriate written informed consent must be obtained;
• Men and women, between the ages of 18 and 70 years old, inclusive, at the time of randomization;
• Diagnosis of SLE as defined by the most recent ACR criteria, including a positive ANA at screening or documented positive ANA (the titer should be at least 1:80) in the past.
• SLE duration of at least six months, as diagnosed by a physician;
• Stable disease, defined as no change in SLE therapy within the previous 30 days; and, in the opinion of the investigator, no anticipated need for a change in SLE therapy will be required while the subject is enrolled in the study;
• Normal or clinically acceptable ECG (12-lead reporting ventricular rate and PR, QRS, QT, QTc) at screening and Day -1 based on the opinion of the investigator;
• Body mass index from 18 to 40 kg/m2 at screening;
• Able and willing to complete entire study according to study schedule.
• Immunizations up to date, with a minimum of tetanus, diphtheria, pertussis (td/Tdap), pneumococcal (polysaccharide) and influenza (during flu season) vaccinations, as determined by the Principal Investigator.

Exclusion Criteria

• Positive serology for HIV antibodies, hepatitis B surface antigen or hepatitis C antibodies (confirmed by PCR or RIBA);
• Have had signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization;
• Evidence of active or latent tuberculosis as assessed by PPD or Quantiferon testing at screening;
• Have donated blood or experienced a loss of blood >500mL within 4 weeks of randomization;
• History of ethanol or drug abuse within the last one year prior to randomization;
• Evidence of significant renal insufficiency, defined by:

The glomerular fitration rate < 50 mL/min using the Cockroft and Gault equation;

• Evidence of liver disease (eg, serum ALT or AST > 2x upper limit of normal);
• Total WBC <3000 x 106/L;
• Neutrophil count < 1500 x106/L
• Platelet count <75,000 x 106/L
• Hemoglobin <10g/dL
• Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of SLE) that would, by it progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures in the medical judgment of the investigator. This includes any age related co-morbidites such as presence of congestive heart failure, angina, chronic obstructive pulmonary disease, asthma, and malignancies (other than resected squamous and basal cell carcinoma of the skin).
• Presence or history of vasculitis (comprising internal organs or extremities or leading to peripheral neuropathy) within the last 3 years, presence or history of active CNS lupus (defined as seizure disorder, cerebral vascular accident, psychosis ascribed to SLE , encephalitis, meningitis, and myelitis) requiring therapy within the last 3 years;
• Uncontrolled hypertension (Blood pressure > 150/95);
• Poorly controlled diabetes (HbA1c > 8%);
• Any history of granulomatous disease including autoimmune granulomatous vasculitis and sarcoidosis;
• Underlying condition that predisposes the subject to infections (eg, history of splenectomy);
• Any disorder or condition that prevents the subject from providing truly informed consent;
• Prior administration of any other biologic that primarily targets the immune system (eg, Lymphostat-B, TACI-Ig, or CTLA4-Ig) in the past 9 months. This includes prior administration of AMG 557;
• Presence of AMG 557 anti-bodies;
• Prior administration of rituximab > 9 months with CD19+ B cells <5/µL;
• Administration of cyclophosphamide (or any other alkylating agent), cyclosporine, tacrolimus, or sirolimus, or > 100 mg/day prednisone or equivalent in the 6 months prior to randomization;
• Participated in an investigational drug trial involving a monoclonal antibody (not targeting the immune system) within 3 months or 5 half-lives, whichever time period is longer, prior to randomization;
• Participated in any another investigational drug or device trial within the previous 30 days or 5 half-lives, whichever time period is longer, prior to randomization;
• Administration of >10 mg/day prednisone (or equivalent) in the 30 days prior to randomization;
• Known sensitivity to mammalian derived products;
• Unwilling to practice an effective method of double-barrier contraception as determined by the investigator for the duration of the study;
• Positive serum hCG at screening or positive urine hCG on D-1; or females who are currently lactating;
• Known allergies to shellfish or any excipients found in KLH;
• Previous immunization with KLH.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Research Site

Anniston, Alabama, United States

Research Site

Phoenix, Arizona, United States

Research Site

San Leandro, California, United States

Research Site

Danbury, Connecticut, United States

Research Site

Miami, Florida, United States

Research Site

Michigan City, Indiana, United States

Research Site

Manhasset, New York, United States

Research Site

Rochester, New York, United States

Research Site

Duncansville, Pennsylvania, United States

Research Site

Amarillo, Texas, United States

Research Site

Dallas, Texas, United States

Research Site

Newmarket, Ontario, Canada

Countries

United States; Canada

References

Sullivan BA, Tsuji W, Kivitz A, Peng J, Arnold GE, Boedigheimer MJ, Chiu K, Green CL, Kaliyaperumal A, Wang C, Ferbas J, Chung JB. Inducible T-cell co-stimulator ligand (ICOSL) blockade leads to selective inhibition of anti-KLH IgG responses in subjects with systemic lupus erythematosus. Lupus Sci Med. 2016 Apr 8;3(1):e000146. doi: 10.1136/lupus-2016-000146. eCollection 2016.

Reference Type: DERIVED

PMID: 27099766 (View on PubMed)

Welcher AA, Boedigheimer M, Kivitz AJ, Amoura Z, Buyon J, Rudinskaya A, Latinis K, Chiu K, Oliner KS, Damore MA, Arnold GE, Sohn W, Chirmule N, Goyal L, Banfield C, Chung JB. Blockade of interferon-gamma normalizes interferon-regulated gene expression and serum CXCL10 levels in patients with systemic lupus erythematosus. Arthritis Rheumatol. 2015 Oct;67(10):2713-22. doi: 10.1002/art.39248.

Reference Type: DERIVED

PMID: 26138472 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20060169

Identifier Type: -

Identifier Source: org_study_id