A Study to Evaluate the Safety and Tolerability of Multiple Intravenous Doses of MEDI 545 in Patients With Systemic Lupus Erythematosus

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00482989
First received: June 4, 2007
Last updated: July 10, 2012
Last verified: July 2012
  Purpose

To evaluate the safety and tolerability of multiple IV doses of the MEDIMUNNE antibody in adult patients with SLE.


Condition Intervention Phase
Lupus
Biological: MEDI 545
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety and Tolerability of Multiple Intravenous Doses of MEDI-545, a Fully Human Anti-Interferon-Alpha Monoclonal Antibody, in Patients With Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • The safety and tolerability of MEDI-545 will be assessed primarily by summarizing AEs and by assessing changes in viral cultures and titers. [ Time Frame: Through Study Day 350. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary endpoints of this study are the PK and IM of multiple IV doses of MEDI-545. PK parameters, such as peak concentration. [ Time Frame: Study day 350. ] [ Designated as safety issue: Yes ]

Enrollment: 183
Study Start Date: June 2007
Study Completion Date: September 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
MEDI-545
Biological: MEDI 545

MEDI-545 is supplied as a sterile liquid containing 0.75 mL of MEDI-545 solution at a concentration of 100 mg/mL in a 3 mL single-use glass vial.

Dosage, frequency and duration: MEDI-545 (0.3, 1.0, 3.0, or 10.0 mg/kg) will be administered via infusion over at least 60 minutes every 2 weeks for 26 weeks.

2
Placebo
Other: Placebo

Dosage form: Placebo is supplied as a sterile liquid containing a 0.75 mL solution in a 3 mL single-use vial.

Dosage, frequency and duration: Placebo (0.3, 1.0, 3.0, or 10.0 mg/kg) will be administered via infusion over at least 60 minutes every 2 weeks for 26 weeks.


Detailed Description:

The primary objective of this study is to evaluate the safety and tolerability of multiple IV doses of MEDI-545 in adult patients with SLE.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female adults ≥ 18 years of age at the time of the first dose of study drug;
  • Written informed consent obtained from the patient; or patient's legal representative;
  • Meet at least 4 of the 11 revised ACR classification criteria for SLE (see Appendix A) (ACR,1999);
  • Have positive ANA test at ≥ 1:80 serum dilution in the past or at screening;
  • Have at least one system with a score of A or two systems with a score of B on the BILAG index at screening, or have a SELENA-SLEDAI score ≥ 6;
  • Sexually active women, unless surgically sterile (including tubal ligation) or at least 2 years post-menopausal, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal, or implanted contraceptives, intrauterine device, diaphragm with spermicide, cervical cap, abstinence, sterile sexual partner) in addition to the use of condoms (male or female condoms with spermicide) from screening through the end of the study. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active men, unless surgically sterile, must likewise practice two effective methods of birth control (condom with spermicide or abstinence) and must use such precautions from Study Day 0 through the end of the study.
  • Ability to complete the study period, including follow-up period through Study Day 350; and
  • Willing to forego other forms of experimental treatment during study.

Exclusion Criteria:

  • Have received MEDI-545 within 120 days prior to screening or have either detectable levels of MEDI-545 or anti-MEDI-545 antibodies (positive at > 1:10 serum dilution) in serum at screening;
  • History of allergy or reaction to any component of the study drug formulation;
  • Have received prednisone > 20 mg/day (or an equivalent dose of another oral corticosteroid)within 14 days before randomization/entry;
  • Have received the following dosages of medications within 28 days before randomization/entry: hydroxychloroquine > 600 mg/day, mycophenolate mofetil > 3 g/day,methotrexate > 25 mg/week, azathioprine > 3 mg/kg/day, or any dose of cyclophosphamide, cyclosporine, or thalidomide;
  • Have received leflunomide >20 mg/day in the 6 months prior to Study Day 0;
  • Have received fluctuating doses of antimalarials, mycophenolate mofetil, methotrexate,leflunomide, or azathioprine within 28 days before randomization/entry or fluctuating doses of NSAIDs or oral corticosteroids within 14 days before randomization/entry;
  • Treatment with any investigational drug therapy within 28 days before randomization/entry into the study, B cell-depleting therapies within 12 months before randomization/entry, or biologic therapies within 30 days or 5 half-lives of the biologic agent, whichever is longer,before randomization/entry into the study;
  • In the investigator's opinion, evidence of clinically significant active infection, including ongoing, chronic infection, within 28 days before randomization/entry;
  • A history of severe viral infection as judged by the investigators, including severe infections of either cytomegalovirus or the herpes family such as disseminated herpes, herpes encephalitis, ophthalmic herpes;
  • Herpes zoster infection within 3 months before randomization/entry;
  • Evidence of infection with hepatitis B or C virus, or HIV-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at screening;
  • Vaccination with live attenuated viruses within 28 days before randomization/entry;
  • Pregnancy (women, unless surgically sterile or at least 2 years post-menopausal, must have a negative serum pregnancy test within 28 days before receiving the study drug and a negative urine pregnancy test on Study Day 0 before receiving the study drug);
  • Breastfeeding or lactating women;
  • History of primary immunodeficiency;
  • History of alcohol or drug abuse < 1 year prior to randomization/entry;
  • History of cancer (except basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy > 1 year prior to randomization/entry);
  • History of active TB infection;
  • History of latent TB infection or newly positive TB skin test (reaction defined as ≥ 10 mm in diameter if not on systemic immunosuppressive medication or ≥ 5 mm if on systemic immunosuppressive medication) without completion of an appropriate course of treatment or with ongoing prophylactic therapy;
  • Elective surgery planned from the time of screening through Study Day 196;
  • At screening blood tests (within 28 days before randomization/entry), any of the following:

    • AST > 2 × upper limit of normal range (ULN), unless caused by SLE, as determined by the investigator,
    • ALT > 2 × ULN,unless caused by SLE, as determined by the investigator,
    • Creatinine > 4.0 mg/dL,
    • Neutrophils "1,500/ μL (< 1.5 × 109/L)"
    • Platelet count "Platelet count < 50,000/ μL (< 50 × 109/L)"
  • History of any disease, evidence of any current disease (other than SLE), any finding upon physical examination, or any laboratory abnormality that, in the opinion of the investigator or medical monitor, may compromise the safety of the patient in the study or confound the analysis of the study; or
  • Any employee of the research site who is involved with the conduct of the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00482989

Locations
United States, Alabama
Research Site
Anniston, Alabama, United States, 36207
United States, California
Research Site
La Jolla, California, United States, 92037-0943
Research Site
Los Angeles, California, United States, 90048
United States, Florida
Research Site
Clearwater, Florida, United States, 37765
Research Site
Fort Lauderdale, Florida, United States, 33334
Research Site
Ocala, Florida, United States, 34474
Research Site
Tampa, Florida, United States, 33614
United States, Louisiana
Research Site
Shreveport, Louisiana, United States, 71130
United States, Maryland
Research Site
Baltimore, Maryland, United States, 21205
Research Site
Bethesda, Maryland, United States, 20892
United States, New York
Research Site
Manhasset, New York, United States, 11030
Research Site
New York, New York, United States, 10003
Research Site
New York, New York, United States, 10021
United States, North Carolina
Research Site
Greenville, North Carolina, United States, 27858
United States, Oklahoma
Research Site
Oklahoma, Oklahoma, United States
United States, Oregon
Research Site
Portland, Oregon, United States, 97223
United States, Texas
Research Site
Dallas, Texas, United States, 75235
Research Site
Dallas, Texas, United States, 75390-8577
Argentina
Research Site
Buenos Aires, Argentina
Research Site
Tucuman, Argentina, T4000AXXL
Brazil
Research Site
Curitiba, PR, Brazil, 80060-240
Research Site
Sao Paulo, Brazil
Chile
Research Site
Santiago, Chile
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Warren Greth, M.D. MedImmune LLC
  More Information

No publications provided by MedImmune LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT00482989     History of Changes
Obsolete Identifiers: NCT00566163
Other Study ID Numbers: MI-CP152
Study First Received: June 4, 2007
Last Updated: July 10, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on April 15, 2014