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About
To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of repeat administration (two doses) of intravenous (IV) ETI-204.
Full description
A double-blind, randomized, placebo-controlled, study in 70 healthy adult subjects. The total duration of the study for each subject will be approximately 220 days divided as follows:
Subjects will be randomized in a 1:1 ratio to one of the following two treatment sequences:
Subjects who qualify for entry into the study following completion of the Screening visit will arrive at the clinical research unit (CRU) on Day -1. The next day, Day 1, qualified subjects will be randomized and will receive a single IV dose of ETI-204. Subjects will be pretreated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the study drug infusion.
Subjects will be discharged from the CRU on Day 2, and will return to the CRU for an additional visit on Day 8.
Subjects will return to the CRU on Day 13 for their second in-unit stay. The next day, Day 14, subjects will be pretreated with 50 mg oral diphenhydramine and will receive study drug according to their randomized treatment assignment. Subjects will be discharged on Day 15 and will return to the CRU for four additional visits on Days 28 (±3 days), 43 (±3 days), 71 (±3 days), and 85 (±3 days).
Subjects will return to the CRU again on Day 119 for their third in-unit stay. On Day 120, subjects will be pretreated with 50 mg oral diphenhydramine and will receive study drug (either ETI 204 or placebo) according to their randomized treatment assignment. Subjects will be discharged on Day 121 and will return to the CRU for five additional visits on Days 128,134, 149, 163, and 191.
The first 20 subjects randomized and treated in the study will be dosed in groups of no more than 4 subjects/day. For the first 8 subjects, dosing of individual subjects on Day 14 and Day 120 will be separated by 30-60 minutes for safety monitoring. If no severe infusion reactions occur in any of the first 8 subjects at the time of the second dose, staggered dosing is not required for the remaining subjects receiving their second dose. Similarly, if no severe infusion reactions occur in any of the first 8 subjects at the time of the third dose, staggered dosing is not required for the remaining subjects receiving their third dose.
Enrollment of additional subjects will be paused until the first 20 subjects have received their second dose of study drug and a blinded review of the available clinical and laboratory AE data up to and including Day 15 is completed for the first 20 subjects. This review will be conducted by the Investigator in conjunction with the Clinical Trial Steering Committee and will focus on the possible development of new or more severe AEs with the Day 14 dose. If the outcome of this review is satisfactory, dosing of additional subjects will be permitted to continue in groups larger than 4 subjects. In the event that significant AEs are observed and unblinding should become necessary, it will be performed by an independent statistician who is not involved with the conduct of the study.
A second blinded safety review will be completed at least two weeks before any subject receives the third dose of study drug, (i.e. before any subject is dosed on Day 120). The Investigator in conjunction with the Clinical Trial Steering Committee will review all AEs seen to date in the study. This review will focus on AE data seen in association with the second infusion (Day14). If the outcome of this review is satisfactory, subjects may receive their third dose of study drug.
A third blinded safety review will be conducted after the initial cohort of 20 subjects has completed Day 121. No additional subjects should receive a third dose of study medication until the Investigator along with the Clinical Trial Steering Committee has completed a blinded safety review of the Day 120 and 121 clinical and laboratory AE data. This review will focus on the development of new or more severe AEs seen with repeat dosing. If the outcome of this review is satisfactory, the remaining subjects may receive their third dose of study drug.
In the event that significant AEs are observed and unblinding becomes necessary it will be performed by an independent statistician who is not involved with the conduct of the study.
Enrollment
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Inclusion criteria
Exclusion criteria
Pregnant or lactating woman
Clinically significant comorbidity that would interfere with completion of the study procedures or objectives or compromise the subject's safety
Seated systolic blood pressure (BP) ≥ 150 mmHg or ≤ 90 mmHg or diastolic BP ≥ 95 mmHg
Use of H1 receptor antagonists (i.e. antihistamines) within 5 days prior to Day 1
Evidence of drug or alcohol abuse as determined by the Investigator within 6 months of Day 1
Positive test result for drugs of abuse (with the exception of medically prescribed drugs) at Screening or on Day -1
Positive test for alcohol at Screening; exclusion is at the Investigator's discretion; subjects who test positive for alcohol at Day -1 are excluded from the study
Treatment with an investigational agent within 30 days or five half-lives of the investigational agent at Day 1 (whichever is longer)
Congenital or acquired immunodeficiency syndrome
Prior solid organ or bone marrow transplant
Positive test for Hepatitis B (surface antigen), Hepatitis C, or human immunodeficiency virus (HIV) at Screening
History of prior treatment for anthrax exposure or prior anthrax infection
Prior immunization with any approved or investigational anthrax vaccine or prior treatment with an approved or investigational anthrax treatment (i.e., ETI-204, raxibacumab, or anthrax immune globulin)
Military personnel deployed in 1990 or after, unless the subject can provide documentation demonstrating they have not previously received any approved or investigational anthrax vaccine
Use of systemic steroids, immunosuppressive agents, anticoagulants, or anti-arrhythmics within 1 year prior to Day 1. A single short course (i.e., less than 14 days) of systemic steroid therapy is allowed provided it concluded more than 6 months prior to Day 1
Donation or loss of > 500 mL of blood within 30 days or plasma within 7 days of Day 1
Prior stroke, epilepsy, relapsing or degenerative central nervous system disease, or relapsing or degenerative ocular disease
Myocardial infarction or acute coronary syndrome in the past 5 years, active angina pectoris, or heart failure (New York Heart Association scale > 1)
History of chronic liver disease
Calculated creatinine clearance (CrCl) of < 30 mL/min using the Cockcroft-Gault equation (see Section 5.1)
Any clinically significant abnormality, in the Investigator's opinion, on electrocardiogram (ECG) or clinical laboratory tests (hematology, clinical chemistry, or urinalysis) at Screening; Out of range results may be repeated to confirm.
History of allergic or hypersensitivity reactions to other therapeutic antibodies or immunoglobulins
History of any malignant neoplasm within the last 5 years, with the exception of adequately treated, localized or in situ non-melanoma carcinoma of the skin (e.g., basal cell carcinoma) or the cervix
Subjects who, in the opinion of the Investigator, are not suitable candidates for enrollment or who may not comply with the requirements of the study
Primary purpose
Allocation
Interventional model
Masking
70 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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