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

NCT ID: NCT00515385

Last Updated: 2022-02-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-08-31
• Study Completion Date: 2009-01-31

Brief Summary

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.

Conditions

West Nile Virus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1a

Cohort 1 completed

Group Type: EXPERIMENTAL

MGAWN1

Intervention Type: DRUG

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

MGAWN1

Intervention Type: DRUG

Single IV dose

1b

Cohort 1 placebo completed

Group Type: PLACEBO_COMPARATOR

MGAWN1

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

Single IV dose

2a

Cohort 2 completed completed

Group Type: EXPERIMENTAL

MGAWN1

Intervention Type: DRUG

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

MGAWN1

Intervention Type: DRUG

Single IV dose

2b

Cohort 2 placebo completed

Group Type: PLACEBO_COMPARATOR

MGAWN1

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

Single IV dose

3a

Cohort 3 active

Group Type: EXPERIMENTAL

MGAWN1

Intervention Type: DRUG

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

MGAWN1

Intervention Type: DRUG

Single IV dose

3b

Cohort 3 placebo

Group Type: PLACEBO_COMPARATOR

MGAWN1

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

Single IV dose

4a

Cohort 4 active

Group Type: EXPERIMENTAL

MGAWN1

Intervention Type: DRUG

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

MGAWN1

Intervention Type: DRUG

Single IV dose

4b

Cohort 4 placebo

Group Type: PLACEBO_COMPARATOR

MGAWN1

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

Single IV dose

5a

Cohort 5 active

Group Type: EXPERIMENTAL

MGAWN1

Intervention Type: DRUG

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

MGAWN1

Intervention Type: DRUG

Single IV dose

5b

Cohort 5 placebo

Group Type: PLACEBO_COMPARATOR

MGAWN1

Intervention Type: DRUG

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

Placebo

Intervention Type: OTHER

Single IV dose

Interventions

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

Intervention Type: DRUG

MGAWN1

Single IV dose

Intervention Type: DRUG

Placebo

Single IV dose

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

MacroGenics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

PAREXEL Phase 1 Unit

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

DMID 06-0090

Identifier Type: -

Identifier Source: secondary_id

CP-MGAWN1-01

Identifier Type: -

Identifier Source: org_study_id