Inhalational Anthrax
Conditions
Keywords
Monoclonal antibody, ETI-204, IM, safety, PK, immunogenicity
Brief 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
Detailed description
Following completion of a Screening visit subjects will arrive at the clinic on Day -1. On Day 1, subjects will be randomized in a 3:1 ratio to receive an IM dose of either ETI-204 or matching placebo, respectively: Cohort 1: 4 subjects randomized to 4 mg/kg ETI-204 or matching placebo Cohort 2: 8 subjects randomized to 8 mg/kg ETI-204 or matching placebo Cohort 3: 8 subjects randomized to 16 mg/kg ETI-204 or matching placebo Cohort 4: 8 subjects randomized to 20 mg/kg ETI-204 or matching placebo Cohort 5: 8 subjects randomized to 24 mg/kg ETI-204 or matching placebo Study drug will be injected bilaterally into the vastus lateralis muscles, with the subject in a supine position. A separate syringe with a 21-gauge,1.5-inch needle will be used for each injection. The number of injections and injection volume will increase with increasing dose allowing for an assessment of increasing IM ETI-204 doses and the tolerability of a larger number of injections and larger injection volume. Subjects will be pretreated with 50 mg oral diphenhydramine approximately 30 minutes prior to administration of study drug. Subjects will be discharged from the study facility on Day 4 following completion of study assessments and will return to the study facility for additional visits on Days 7, 10, 15 (±3 days), 29 (±3 days), 43 (±3 days), and 71 (±4 days). Decisions to dose-escalate will be made by the investigator(s) in conjunction with the sponsor and will be based solely on the available safety and local tolerability data up to and including Day 4.
Interventions
BIOLOGICALETI-204
monoclonal antibody
OTHERPlacebo
Placebo for ETI-204
Sponsors
Elusys Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, 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.
Intervention model description
Dose escalation study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Adverse Events | Up to 71 (+/- 4) days or for 30 additional days after the final study visit for subjects with ongoing adverse events at the final scheduled study visit, for each group. | Safety was assessed for all subjects in the Safety Population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical examinations, injection site assessments, skin assessments for presence/absence of rash, and adverse events (AEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg. | Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) | Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg. | Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) | Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg. | Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Maximum Observed Plasma Concentration of ETI-204 (Cmax) | Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg. | Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Apparent Clearance (CL/F) | Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg. | Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
| Number of Participants With Anti-ETI-204 Antibodies | Pre-dose and on Days 10, 43, and 71 after the IM injection of ETI-204 or placebo on Day 1. | Blood samples were collected and serum samples were assayed at an initial dilution of 1:10. Samples that were positive at the 1:10 dilution were serially diluted 1:2 and assayed until a negative result was attained. The titer of the most dilute sample yielding a positive result was recorded as the titer for that time point. Immunogenicity was measured by the number of participants in each study arm with anti-ETI-204 antibody values at Days 8, 43 or 71 ≥ 4-times higher than at baseline, or if the titer was negative at baseline, the post-treatment sample(s) required a titer of at least 1:20 for it to be considered positive. |
| Half-life (t1/2) | Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg. | Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL. |
Countries
United States
Participant flow
Recruitment details
Study started July 26, 2013. Study completed July 03, 2014. Conducted at a Phase 1 Clinical Research Unit
Participants by arm
| Arm | Count |
|---|---|
| Placebo IM
Placebo: Placebo comparator | 9 |
| ETI-204 IM
ETI-204: monoclonal antibody | 27 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Cohort 5 - ETI-204 24 mg/kg or Placebo | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | ETI-204 | Total |
|---|---|---|---|
| Age, Continuous | 45.8 years STANDARD_DEVIATION 11.53 | 47.4 years STANDARD_DEVIATION 14.31 | 47.0 years STANDARD_DEVIATION 13.5 |
| BMI | 24.92 kg/m2 STANDARD_DEVIATION 2.983 | 26.04 kg/m2 STANDARD_DEVIATION 3.454 | 25.76 kg/m2 STANDARD_DEVIATION 3.337 |
| Body weight | 67.71 kg STANDARD_DEVIATION 13.406 | 76.33 kg STANDARD_DEVIATION 12.351 | 74.2 kg STANDARD_DEVIATION 12.989 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 5 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 21 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Height | 164.18 cm STANDARD_DEVIATION 8.859 | 171.01 cm STANDARD_DEVIATION 8.062 | 169.3 cm STANDARD_DEVIATION 8.672 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 13 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 12 Participants | 17 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 16 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 5 / 9 | 3 / 3 | 1 / 6 | 1 / 6 | 2 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 9 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Participants Who Experienced Adverse Events
Safety was assessed for all subjects in the Safety Population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical examinations, injection site assessments, skin assessments for presence/absence of rash, and adverse events (AEs).
Time frame: Up to 71 (+/- 4) days or for 30 additional days after the final study visit for subjects with ongoing adverse events at the final scheduled study visit, for each group.
Population: All subjects who received either ETI-204 or placebo were included in the Safety Population. Placebo subject were included in each cohort (one in Cohort 1 and two each in Cohorts 2, 3 ,4 and 5). Safety data are summarized separately for subjects who received ETI-204 in each dose group and for the pooled placebo group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced Adverse Events | 5 Participants |
| Cohort 1 | Number of Participants Who Experienced Adverse Events | 3 Participants |
| Cohort 2 | Number of Participants Who Experienced Adverse Events | 1 Participants |
| Cohort 3 | Number of Participants Who Experienced Adverse Events | 1 Participants |
| Cohort 4 | Number of Participants Who Experienced Adverse Events | 2 Participants |
| Cohort 5 | Number of Participants Who Experienced Adverse Events | 2 Participants |
Secondary
Apparent Clearance (CL/F)
Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.
Population: The PK Population consisted of all subjects who received ETI-204 IM and had at least one valid PK parameter.1 subject in Cohort 2 was excluded because the dosing record was missing. For 4 subjects (1 in Cohort 2, 1 in Cohort 4, and 2 in Cohort 5) the extrapolated portion of AUC0-inf was \>20%; therefore, AUC0-inf-based parameters were not recorded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Apparent Clearance (CL/F) | 0.410 Liters/day | Standard Deviation 0.0545 |
| Cohort 1 | Apparent Clearance (CL/F) | 0.415 Liters/day | Standard Deviation 0.117 |
| Cohort 2 | Apparent Clearance (CL/F) | 0.445 Liters/day | Standard Deviation 0.113 |
| Cohort 3 | Apparent Clearance (CL/F) | 0.382 Liters/day | Standard Deviation 0.0736 |
| Cohort 4 | Apparent Clearance (CL/F) | 0.478 Liters/day | Standard Deviation 0.202 |
Secondary
Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf)
Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.
Population: The PK Population consisted of all subjects who received ETI-204 IM and had at least one valid PK parameter. 1 subject in Cohort 2 was excluded because the dosing record was missing. For 4 subjects (1 in Cohort 2, 1 in Cohort 4. and 2 in Cohort 5) the extrapolated portion of AUC0-inf was \>20%; therefore, AUC0-inf was not recorded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) | 819 µg.day/mL | Standard Deviation 85.9 |
| Cohort 1 | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) | 1580 µg.day/mL | Standard Deviation 441 |
| Cohort 2 | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) | 3200 µg.day/mL | Standard Deviation 755 |
| Cohort 3 | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) | 4220 µg.day/mL | Standard Deviation 1360 |
| Cohort 4 | Area Under the Concentration-Time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) | 3960 µg.day/mL | Standard Deviation 823 |
Secondary
Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last)
Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.
Population: The PK Population consisted of all subjects who received ETI-204 IM and had at least one valid PK parameter. One subject in Cohort 2 was excluded from the PK population because the dosing record was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) | 774 µg.day/mL | Standard Deviation 92.3 |
| Cohort 1 | Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) | 1540 µg.day/mL | Standard Deviation 328 |
| Cohort 2 | Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) | 2890 µg.day/mL | Standard Deviation 578 |
| Cohort 3 | Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) | 3660 µg.day/mL | Standard Deviation 945 |
| Cohort 4 | Area Under the Concentration-Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-last) | 3740 µg.day/mL | Standard Deviation 570 |
Secondary
Half-life (t1/2)
Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.
Population: The PK Population consisted of all subjects who received ETI-204 IM and had at least one valid PK parameter. One subject in Cohort 2 was excluded from the PK Population because the dosing record was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Half-life (t1/2) | 16.0 days | Standard Deviation 1.6 |
| Cohort 1 | Half-life (t1/2) | 20.2 days | Standard Deviation 8.47 |
| Cohort 2 | Half-life (t1/2) | 19.6 days | Standard Deviation 4.1 |
| Cohort 3 | Half-life (t1/2) | 23.3 days | Standard Deviation 6.17 |
| Cohort 4 | Half-life (t1/2) | 20.0 days | Standard Deviation 7.2 |
Secondary
Maximum Observed Plasma Concentration of ETI-204 (Cmax)
Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.
Population: The Pharmacokinetic (PK) Population consisted of all subjects who received ETI-204 IM and had at least one valid PK parameter. One subject in Cohort 2 was excluded from the PK Population because the dosing record was missing.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 24.9 µg/mL | Standard Deviation 4.7 |
| Cohort 1 | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 54.8 µg/mL | Standard Deviation 6.45 |
| Cohort 2 | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 105 µg/mL | Standard Deviation 22.5 |
| Cohort 3 | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 118 µg/mL | Standard Deviation 28.2 |
| Cohort 4 | Maximum Observed Plasma Concentration of ETI-204 (Cmax) | 154 µg/mL | Standard Deviation 32.4 |
Secondary
Number of Participants With Anti-ETI-204 Antibodies
Blood samples were collected and serum samples were assayed at an initial dilution of 1:10. Samples that were positive at the 1:10 dilution were serially diluted 1:2 and assayed until a negative result was attained. The titer of the most dilute sample yielding a positive result was recorded as the titer for that time point. Immunogenicity was measured by the number of participants in each study arm with anti-ETI-204 antibody values at Days 8, 43 or 71 ≥ 4-times higher than at baseline, or if the titer was negative at baseline, the post-treatment sample(s) required a titer of at least 1:20 for it to be considered positive.
Time frame: Pre-dose and on Days 10, 43, and 71 after the IM injection of ETI-204 or placebo on Day 1.
Population: All subjects in the Safety Population who received either ETI-204 IM or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
| Cohort 1 | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
| Cohort 2 | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
| Cohort 3 | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
| Cohort 4 | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
| Cohort 5 | Number of Participants With Anti-ETI-204 Antibodies | 0 Participants |
Secondary
Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)
Blood samples were obtained and serum concentrations were determined for free ETI-204 using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time frame: Pre-dose and 1.5, 4, 8, 24, 36, 48, 72 hours after the IM injection of ETI-204 on Day 1, and on Days (7), 10, 15, 29, 43, and 71. A Day 7 sample was not included in the profile until the dose had escalated to 20 mg/kg.
Population: The PK Population consisted of all subjects who received ETI-204 IM and had at least one valid PK parameter. One subject in Cohort 2 was excluded from the PK Population because the dosing record was missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 9.00 days |
| Cohort 1 | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 9.00 days |
| Cohort 2 | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 6.00 days |
| Cohort 3 | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 6.00 days |
| Cohort 4 | Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) | 6.00 days |