Safety, Tolerability and PK of Repeat Administration of Intravenous ETI-204 in Adult Volunteers
Condition: Inhalational Anthrax
MeSH terms: Anthrax
Intervention: ETI-204; Placebo
Intervention description: Monoclonal Antibody; Placebo for ETI-204
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Seventy 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
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Study drug will be prepared by an unblinded pharmacist not involved with the conduct of the study. The pharmacist will assign the correct study drug (16 mg/kg ETI-204 or placebo) to each subject according to the randomization scheme.
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: anthrax, monoclonal antibody, ETI-204, safety, PK

Summary:

      To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of repeat
      administration (two doses) of intravenous (IV) ETI-204.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Females or males ≥ 18 years of age

          2. All females, regardless of childbearing potential, must have a negative serum beta
             human chorionic gonadotropin (β-hCG) pregnancy test at Screening and Day -1

          3. Females of childbearing potential (i.e., not postmenopausal or surgically sterile)
             must agree to practice abstinence or to use a medically accepted method of
             contraception from the time of Screening through 30 days after the final study visit.
             Acceptable methods of contraception include diaphragm with spermicide; sponge with
             spermicide; condom with spermicide; or intrauterine device with condom or spermicide.
             The following contraceptive methods are acceptable only when used with a condom and
             spermicide: birth control pills, birth control patches, vaginal ring, hormone under
             the skin, or hormone injections

          4. Postmenopausal females, defined as females who have had amenorrhea for at least 12
             months either naturally or following cessation of all exogenous hormonal treatments,
             and have a follicle-stimulating hormone (FSH) level of > 40 mIU/mL at Screening

          5. Females who have undergone surgical sterilization, including hysterectomy, bilateral
             oophorectomy, bilateral salpingectomy, tubal ligation, or tubal essure

          6. Males must agree to practice abstinence or use a condom with spermicide and refrain
             from sperm donation during the study and for 30 days after the final study visit

          7. Provide written informed consent

          8. Willing to comply with study restrictions

        Exclusion Criteria:

          1. Pregnant or lactating woman

          2. Clinically significant comorbidity that would interfere with completion of the study
             procedures or objectives or compromise the subject's safety

          3. Seated systolic blood pressure (BP) ≥ 150 mmHg or ≤ 90 mmHg or diastolic BP ≥ 95 mmHg

          4. Use of H1 receptor antagonists (i.e. antihistamines) within 5 days prior to Day 1

          5. Evidence of drug or alcohol abuse as determined by the Investigator within 6 months of
             Day 1

          6. Positive test result for drugs of abuse (with the exception of medically prescribed
             drugs) at Screening or on Day -1

          7. 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

          8. Treatment with an investigational agent within 30 days or five half-lives of the
             investigational agent at Day 1 (whichever is longer)

          9. Congenital or acquired immunodeficiency syndrome

         10. Prior solid organ or bone marrow transplant

         11. Positive test for Hepatitis B (surface antigen), Hepatitis C, or human
             immunodeficiency virus (HIV) at Screening

         12. History of prior treatment for anthrax exposure or prior anthrax infection

         13. 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)

         14. 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

         15. 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

         16. Donation or loss of > 500 mL of blood within 30 days or plasma within 7 days of Day 1

         17. Prior stroke, epilepsy, relapsing or degenerative central nervous system disease, or
             relapsing or degenerative ocular disease

         18. Myocardial infarction or acute coronary syndrome in the past 5 years, active angina
             pectoris, or heart failure (New York Heart Association scale > 1)

         19. History of chronic liver disease

         20. Calculated creatinine clearance (CrCl) of < 30 mL/min using the Cockcroft-Gault
             equation (see Section 5.1)

         21. 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.

         22. History of allergic or hypersensitivity reactions to other therapeutic antibodies or
             immunoglobulins

         23. 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

         24. 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

             -