Intramuscular Dose-Escalation Study With 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: Sequential Assignment
Intervention model description: Dose escalation study
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: The investigator, clinical research unit staff, and subjects will be blinded to treatment assignment. The randomization list will be made available to the pharmacist preparing study drug.
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Monoclonal antibody, ETI-204, IM, safety, PK, immunogenicity

Summary:

      This study is to evaluate the safety, local tolerability, pharmacokinetics (PK) and
      immunogenicity of escalating single intramuscular (IM) doses of ETI-204 in healthy volunteers
    

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/cervical cap 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 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 to refrain
             from sperm donation from Screening 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. Body weight >100 kg;

          2. Body mass index ≥32 kg/m2;

          3. Pregnant or lactating female;

          4. Clinically significant comorbidity that would interfere with completion of the study
             procedures or objectives, or compromise the subject's safety;

          5. Supine systolic blood pressure (BP) ≥150 mmHg or ≤90 mmHg or diastolic BP ≥95 mmHg;

          6. Use of H1 receptor antagonists (i.e., antihistamines) within 5 days prior to Day 1;

          7. Evidence of drug or alcohol abuse within 6 months of Day 1 as determined by the
             Investigator;

          8. Positive test result for drugs of abuse (with the exception of medically prescribed
             drugs) at Screening or on Day -1;

          9. Positive test for alcohol at Screening, subject to Investigator's discretion. Subjects
             who test positive for alcohol at Day -1 are excluded from the study;

         10. Treatment with an investigational agent within 30 days or 5 half-lives of the
             investigational agent at Day 1 (whichever is longer);

         11. Congenital or acquired immunodeficiency syndrome;

         12. Prior solid organ or bone marrow transplant;

         13. Positive test for Hepatitis B (surface antigen), Hepatitis C, or human
             immunodeficiency virus (HIV) at Screening;

         14. History of prior treatment for anthrax exposure or prior anthrax infection;

         15. Prior immunization with any approved or investigational anthrax vaccine or prior
             treatment with an investigational anthrax treatment (e.g., ETI-204, raxibacumab, or
             anthrax immune globulin);

         16. Military personnel deployed in 1990 or after, unless the subject can provide
             documentation demonstrating he or she has not previously received any approved or
             investigational anthrax vaccine;

         17. 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;

         18. Donation or loss of >500 mL of blood within 30 days or plasma within 7 days of Day 1;

         19. Prior stroke, epilepsy, relapsing or degenerative central nervous system disease, or
             relapsing or degenerative ocular disease;

         20. Myocardial infarction or acute coronary syndrome in the past 5 years, active angina
             pectoris, or heart failure (New York Heart Association scale >1);

         21. History of chronic liver disease;

         22. Calculated creatinine clearance of <30 mL/min using the Cockcroft-Gault equation;

         23. 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 tests may be repeated to confirm;

         24. History of allergic or hypersensitivity reaction or hives to other therapeutic
             antibodies or immunoglobulins;

         25. 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;

         26. 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.

         27. Platelet count <140 K/µL;

         28. Prothrombin time/international normalized ratio or activated partial thromboplastin
             time >1.2 X the upper limit of normal at Screening or Day -1;

         29. Poor muscle mass as determined by the Investigator;

         30. Family or personal history of a bleeding disorder;

         31. History of unexplained bleeding;

         32. Use of any anticoagulant or anti-platelet drug for 3 months prior to Screening. At the
             discretion of the Investigator, daily aspirin may be taken for general health reasons.