Inhalational Anthrax Clinical Trial
Official title:
A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Repeat Administration of Intravenous ETI-204 in Adult Volunteers
To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of repeat administration (two doses) of intravenous (IV) ETI-204.
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:
- Screening: Days -28 to -2
- Three In-Unit Stays: Days -1 to 2; Days 13 to 15; and Days 119 to 121
- Out-of-Unit Visit Days: Day 8 (±2 days); Day 28 (±3 days); Day 43 (±3 days); Day 71 (±3
days); Day 85 (±3 days); Day 128 (±3 days); Day 134 (±3 days); Day 149 (±3 days); and
Day 163 (±3 days)
- Final Visit: Day 191 (±3 days)
Subjects will be randomized in a 1:1 ratio to one of the following two treatment sequences:
- Sequence A: ETI-204 on Days 1 and 14 and placebo on Day 120
- Sequence B: ETI-204 on Days 1 and 120 and placebo on Day 14
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.
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