A Trial to Evaluate the Safety of a Single Intravenous Infusion of MGAWN1 in Healthy Adults

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
MacroGenics
ClinicalTrials.gov Identifier:
NCT00515385
First received: August 9, 2007
Last updated: July 14, 2009
Last verified: July 2009
  Purpose

The primary purpose of this phase 1, double-blind, cohort study is to evaluate the safety, tolerability, and pharmacokinetics of escalating doses of MGAWN1 administered as a single intravenous (IV) infusion to healthy adults. Subjects will be enrolled sequentially into one of 5 dose-level cohorts, with 8 subjects in each cohort. Six subjects in each cohort will receive MGAWN1 (a Neutralizing, Humanized, Monoclonal Antibody (IgG1k) to West Nile Virus) and 2 will receive a saline control.


Condition Intervention Phase
West Nile Virus
Drug: MGAWN1
Other: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Dose-Escalation Cohort Study to Evaluate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of MGAWN1, a Neutralizing, Humanized, Monoclonal Antibody (IgG1k) to West Nile Virus, in Healthy Adults

Resource links provided by NLM:


Further study details as provided by MacroGenics:

Primary Outcome Measures:
  • The incidence of adverse events and serious adverse events through the end of the study. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The determination of pharmacokinetic (PK) parameters and immunogenicity of MGAWN1. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: August 2007
Study Completion Date: January 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1a
Cohort 1 completed
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Drug: MGAWN1
Single IV dose
Placebo Comparator: 1b
Cohort 1 placebo completed
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Other: Placebo
Single IV dose
Experimental: 2a
Cohort 2 completed completed
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Drug: MGAWN1
Single IV dose
Placebo Comparator: 2b
Cohort 2 placebo completed
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Other: Placebo
Single IV dose
Experimental: 3a
Cohort 3 active
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Drug: MGAWN1
Single IV dose
Placebo Comparator: 3b
Cohort 3 placebo
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Other: Placebo
Single IV dose
Experimental: 4a
Cohort 4 active
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Drug: MGAWN1
Single IV dose
Placebo Comparator: 4b
Cohort 4 placebo
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Other: Placebo
Single IV dose
Experimental: 5a
Cohort 5 active
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Drug: MGAWN1
Single IV dose
Placebo Comparator: 5b
Cohort 5 placebo
Drug: MGAWN1

Eight subjects per cohort, each receives a single IV infusion of MGAWN1 of saline control on study day 0 (6 MGAWN1, 2 saline control.

Cohort 1 - 0.3 mg/kg Cohort 2 - 1 mg/kg Cohort 3 - 3 mg/kg Cohort 4 - 10 mg/kg Cohort 5 - 30 mg/kg

Other: Placebo
Single IV dose

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Written informed consent obtained from the subject including consent for the use of research-related health information, before performance of any study-related procedure including screening procedures
  2. Healthy adult male or female subjects aged 18-65 years, with a body mass index (BMI) of 18-32 kg/m2
  3. Subjects must be physically healthy as determined by the investigator based on medical history, physical examination, ECG, and clinical laboratory tests within laboratory normal ranges. To be considered normal, the following results must pertain:

    • The serum potassium must be within normal limits.
    • Hemoglobin must be ≥12 mg/dl; ANC must be 1,500-upper limit of normal (ULN); platelets must be 130,000-500,000 μL; and sodium must be 130-150 moles/L.
    • Each of these tests must not exceed the upper limit of normal: WBC, creatinine, and (provided asymptomatic) fasting blood glucose.
    • Bilirubin must be ≤ 2x ULN, ALT ≤ 1.25x ULN, and AST ≤1.25x ULN
    • Urinalysis: glucose negative and protein ≤ 20 mg/dl.
  4. Have adequate venous access
  5. Have negative assays for human immunodeficiency virus (HIV), hepatitis B virus (HBsAg) and hepatitis C virus (HCV)
  6. Women of childbearing potential will not be breastfeeding and will have a negative serum pregnancy test within 21 days of study drug administration as well as on Study Day −1
  7. Women of childbearing potential (including peri-menopausal women who have had a menstrual period within 1 year of enrollment) must be using appropriate birth control (defined as a method with low failure rate, i.e., less than 1% per year, when used consistently and correctly such as implants, injectables, some intrauterine contraceptive devices, sexual abstinence, or a vasectomized partner) during the entire duration of study participation. Use of contraceptive medications is allowed during the study. Women who have undergone a total hysterectomy or are postmenopausal are eligible.
  8. In the opinion of the investigator, the subject is capable of understanding and complying with the protocol
  9. Subject is a non-smoker, i.e., has refrained from any tobacco usage, including smokeless tobacco, nicotine patches, etc. for 6 months before study entry
  10. Subject's normal alcohol consumption does not exceed 3 units per day if male or does not exceed 2 units per day if female. Both male and female subjects will be permitted to consume no more than 2 units of alcohol per day throughout the study. (One unit of alcohol is equivalent to 1 ounce of hard liquor, or 4 ounces of wine, or 12 ounces of beer.)
  11. Willing to forego other forms of experimental treatment during the study

Exclusion Criteria:

  1. Subject is unwilling or unable to comply with the protocol during the study period or to cooperate fully with the investigator or the site personnel
  2. Subject has a significant organ abnormality or disease
  3. Subject is considering or scheduled to have any surgical procedure during the duration of the study
  4. Subject has an active malignancy or history of solid, metastatic, or hematologic malignancy with the exception of basal or squamous cell carcinoma of the skin that has been removed
  5. Subject has donated or lost more than a unit of blood within 30 days before screening
  6. Subject has a positive qualitative urine drug test at screening or an abnormal blood alcohol test (≥ 10mg/dL) on Study Day −1
  7. Subject has received any other investigational drug or investigational biologically derived pharmaceutical agent within 60 days before screening
  8. Subject has a history of seizure, chronic headache, viral encephalitis, or clinically significant infection (including viral) in the 14 days before dosing
  9. Subject is receiving any concomitant medication requiring a prescription, except for contraceptives
  10. Use of OTC preparations, herbal remedies or nutritional supplement (other than calcium and vitamin D) within the 7 days before study drug administration
  11. Subject has ongoing drug abuse/dependence (including alcohol); or recent history (over the past 5 years) of, or treatment for, alcohol or drug abuse
  12. Subject has a significant allergy to food or drugs
  13. Currently symptomatic seasonal allergies, or history of anaphylaxis, asthma, dermatographism or eczema
  14. Subject has any condition(s) that in the investigator's opinion would warrant exclusion from the study or prevent the subject from completing the study
  15. Subject is unable to understand spoken and/or written English or any other language in which a certified translation of the informed consent is available
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00515385

Locations
United States, Maryland
PAREXEL Phase 1 Unit
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
MacroGenics
  More Information

No publications provided

Responsible Party: Stanley R. Pillemer, MD, MacroGenics, Inc.
ClinicalTrials.gov Identifier: NCT00515385     History of Changes
Other Study ID Numbers: CP-MGAWN1-01, DMID 06-0090
Study First Received: August 9, 2007
Last Updated: July 14, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by MacroGenics:
Randomized
Double-Blind
Dose-Escalation
Cohort Study

ClinicalTrials.gov processed this record on August 28, 2014