Safety, Tolerability, and PK of a Single Intravenous Dose of ETI-204 in Adult Volunteers

• Sponsor: Elusys Therapeutics (Other)
• Overall Status: Completed
• CT.gov ID: NCT01929226
• Collaborator: (none)
• Enrollment: 280
• Location: 1
• Arms: 2
• Duration (Months): 4.7
• Patients Per Site Per Month: 59.6

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability and pharmacokinetics (PK) of a single intravenous (IV) dose of ETI-204 in adult volunteers.

Condition or Disease	Intervention/Treatment	Phase
Inhalational Anthrax	Biological: ETI-204; Other: Placebo	Phase 1

Detailed Description

A double-blind, randomized, placebo-controlled study of a single IV dose of 16 mg/kg ETI-204 in adult volunteers (210 subjects ETI-204; 70 subjects placebo).

The total duration of the study for each subject will be approximately 100 days divided as follows:

Screening: Days -28 to -2; In-unit Phase: Day -1, Day 1, and Day 2; Out-of-unit Visits: Day 8 (±2 days); Day 15 (±3 days); Day 29 (±3 days); Day 43 (±3 days); Final Visit: Day 71 (±4 days).

Following completion of a screening visit subjects who qualify for entry into the study will be randomized to receive either ETI-204 or matching placebo on Day 1 in a 3:1 ratio. Subjects will be discharged from the clinic on Day 2 following completion of study assessments and will return for five additional visits on Days 8, 15, 29, 43 and 71.

The first 12 subjects will be dosed in groups of no more than 4 subjects/day. A blinded safety review of the available clinical and laboratory AE data up to and including Day 2 will be completed for the first 12 subjects before any additional subjects are dosed. This review will be conducted by the Investigator in conjunction with the Clinical Trial Steering Committee. If the outcome of this review is satisfactory, dosing of additional subjects will be permitted to continue and subjects may be dosed in group sizes larger than 4.

After Amendment 1, premedication with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of study drug infusion was required.

Study Design

• Study Type: Interventional
• Actual Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: A Double-Blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Dose of ETI-204 in Adult Volunteers
• Study Start Date: Jul 9, 2013
• Actual Primary Completion Date: Nov 29, 2013
• Actual Study Completion Date: Nov 29, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ETI-204 A single intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Day 1	Biological: ETI-204; Monoclonal Antibody
Placebo Comparator: Placebo for ETI-204 A single intravenous dose of ETI-204-placebo infused over 90 minutes on Day 1	Other: Placebo; Placebo for ETI-204

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced Adverse Events [Up to 71 days or 101 days (30 days after the final study visit) for subjects with ongoing adverse events at the final 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, skin assessments, infusion site assessments, and adverse events.

Secondary Outcome Measures

1. Maximum Observed Plasma Concentration of ETI-204 (Cmax) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

2. Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

3. Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

4. Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

5. Terminal Half-life (t1/2) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

6. Systemic Clearance (CL) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

7. Volume of Distribution (Vd) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

8. Volume of Distribution at Steady State (Vss) [On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.]

   Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

9. Number of Participants With Anti-ETI-204 Antibodies [On Day 1 prior to the start of infusion and on Days 8, 43, and 71.]

   Serum anti-ETI-204 antibody titers were determined for all subjects in the safety population. 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 post-treatment ≥ 4-times higher than baseline at Day 8, 43 or 71, 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 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 subject to 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 of Day 1 or within 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 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

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 (i.e., 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Inc.	Dallas	Texas	United States	75247

Sponsors and Collaborators

• Elusys Therapeutics

Investigators

• Principal Investigator: Alex King, MD, Covance
• Principal Investigator: Lori Sieboldt, MD, Covance Clinical Research - Evansville, IN
• Principal Investigator: Debra Mandarino, MD, Covance Research, Madison, WI
• Principal Investigator: H. Frank Farmer, PhD, MD, Covance Research - Daytona Beach, Fl

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Elusys Therapeutics
• ClinicalTrials.gov Identifier: NCT01929226
• Other Study ID Numbers: AH104
• First Posted: Aug 27, 2013
• Last Update Posted: Apr 8, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Elusys Therapeutics: anthrax, monoclonal antibody, ETI-204, safety, PK
• Additional relevant MeSH terms: Anthrax

Study Results

Participant Flow

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Intravenously (IV), single dose Placebo: Placebo comparator
Period Title: Overall Study
STARTED	210	70
COMPLETED	205	69
NOT COMPLETED	5	1

Baseline Characteristics

Arm/Group Title	ETI-204	Placebo	Total
Arm/Group Description	Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Intravenously (IV), single dose Placebo: Placebo comparator	Total of all reporting groups
Overall Participants	210	70	280
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.4 (15.59)	41.5 (13.90)	42.2 (15.17)
Sex: Female, Male (Count of Participants)
Female	104 49.5%	32 45.7%	136 48.6%
Male	106 50.5%	38 54.3%	144 51.4%
Region of Enrollment (participants) [Number]
United States	210 100%	70 100%	280 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced Adverse Events
Description	Safety was assessed for all subjects in the safety population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical examinations, skin assessments, infusion site assessments, and adverse events.
Time Frame	Up to 71 days or 101 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each group.

Outcome Measure Data

Analysis Population Description

All randomized participants who received study drug.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	210	70
Count of Participants [Participants]	88 41.9%	27 38.6%

2. Secondary Outcome

Title	Maximum Observed Plasma Concentration of ETI-204 (Cmax)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

Of the 210 participants who received ETI-204, 202 were included in the PK population. One was excluded due to missing dosing record and 7 received partial doses of ETI-204 (6 discontinued study drug due to an AE and one received a partial dose because of mechanical issues with the infusion pump).

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	202	0
Mean (Standard Deviation) [µg/mL]	400 (91.2)

3. Secondary Outcome

Title	Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

Of the 210 participants who received ETI-204, 202 were included in the PK population. One was excluded due to missing dosing record and 7 received partial doses of ETI-204 (6 discontinued study drug due to an AE and one received a partial dose because of mechanical issues with the infusion pump).

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	202	0
Median (Full Range) [days]	0.0782

4. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

Of the 210 participants who received ETI-204, 202 were included in the PK population. Reasons for exclusion were: missing dosing record (1), discontinued study drug due to an AE (6) and mechanical issues with the infusion pump (1). 3 additional participants were excluded from the AUC0-last calculation because of missing PK collection time points.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	199	0
Mean (Standard Deviation) [µg.day/mL]	4770 (1160)

5. Secondary Outcome

Title	Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

In addition, for several participants, certain PK parameter values were set to missing for the purposes of calculating descriptive statistics in the primary analysis, in accordance with the SAP. The extrapolated portion of AUC(0-inf) exceeded 20% of AUC(0-inf) in 8 participants, therefore, AUC(0-inf) was not reported for these individuals.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	191	0
Mean (Standard Deviation) [µg.day/mL]	5170 (1360)

6. Secondary Outcome

Title	Terminal Half-life (t1/2)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

In addition, for several participants, certain PK parameter values were set to missing for the purposes of calculating descriptive statistics in the primary analysis, in accordance with the SAP. ETI-204 t1/2 values were not reported for 6 participants as they were greater than 50% of the 71-day sample collection interval.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	193	0
Mean (Standard Deviation) [days]	20.2 (5.26)

7. Secondary Outcome

Title	Systemic Clearance (CL)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

In addition, for several participants, certain PK parameter values were set to missing for the purposes of calculating descriptive statistics in the primary analysis, in accordance with the SAP. The extrapolated portion of AUC(0-inf) exceeded 20% of AUC(0-inf) in 8 participants, therefore, CL was not reported for these individuals.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	191	0
Mean (Standard Deviation) [Liters/day]	0.270 (0.0886)

8. Secondary Outcome

Title	Volume of Distribution (Vd)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

In addition, for several participants, certain PK parameter values were set to missing for the purposes of calculating descriptive statistics in the primary analysis, in accordance with the SAP. The extrapolated portion of AUC(0-inf) exceeded 20% of AUC(0-inf) in 8 participants, therefore, Vd was not reported for these individuals.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	191	0
Mean (Standard Deviation) [Liters]	7.41 (1.90)

9. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss)
Description	Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.
Time Frame	On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.

Outcome Measure Data

Analysis Population Description

In addition, for several participants, certain PK parameter values were set to missing for the purposes of calculating descriptive statistics in the primary analysis, in accordance with the SAP. The extrapolated portion of AUC(0-inf) exceeded 20% of AUC(0-inf) in 8 participants, therefore, Vss was not reported for these individuals.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	191	0
Mean (Standard Deviation) [Liters]	6.34 (1.55)

10. Secondary Outcome

Title	Number of Participants With Anti-ETI-204 Antibodies
Description	Serum anti-ETI-204 antibody titers were determined for all subjects in the safety population. 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 post-treatment ≥ 4-times higher than baseline at Day 8, 43 or 71, 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	On Day 1 prior to the start of infusion and on Days 8, 43, and 71.

Outcome Measure Data

Analysis Population Description

All participants who received study drug and were included in the safety population.

Arm/Group Title	ETI-204	Placebo
Arm/Group Description	Participants were administered a single intravenous (IV) infusion of 16 mg/kg ETI-204 in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 147(70%) participants were premedicated with 50 mg oral diphenhydramine approximately 30	Participants were administered a single intravenous (IV) infusion of ETI-204 Placebo in 0.9% sterile sodium chloride in a total volume of 250 mL over 90 minutes. , Following a protocol amendment, 48(68.6%) participants were premedicated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the infusion.
Measure Participants	210	70
Count of Participants [Participants]	2 1%	0 0%

Adverse Events

Time Frame	Up to 71 days or 101 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each group.
Arm/Group Title	ETI-204		Placebo
Arm/Group Description	Intravenously (IV), single dose ETI-204: Monoclonal Antibody		Intravenously (IV), single dose Placebo: Placebo comparator
All Cause Mortality
	ETI-204		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/210 (0%)		0/70 (0%)
Serious Adverse Events
	ETI-204		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/210 (0%)		1/70 (1.4%)
Reproductive system and breast disorders
Ovarian Cyst	0/210 (0%)	0	1/70 (1.4%)	1
Other (Not Including Serious) Adverse Events
	ETI-204		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/210 (24.8%)		18/70 (25.7%)
Gastrointestinal disorders
Diarrhoea	0/210 (0%)		2/70 (2.9%)
Nausea	5/210 (2.4%)		2/70 (2.9%)
General disorders
Infusion site erythema	0/210 (0%)		2/70 (2.9%)
Pain	3/210 (1.4%)		2/70 (2.9%)
Vessel puncture site bruise	7/210 (3.3%)		1/70 (1.4%)
Infections and infestations
Upper respiratory tract infection	5/210 (2.4%)		2/70 (2.9%)
Urinary tract infection	0/210 (0%)		2/70 (2.9%)
Musculoskeletal and connective tissue disorders
Back pain	1/210 (0.5%)		3/70 (4.3%)
Nervous system disorders
Headache	21/210 (10%)		4/70 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	6/210 (2.9%)		0/70 (0%)
Skin and subcutaneous tissue disorders
Pruritus	10/210 (4.8%)		1/70 (1.4%)
Rash	5/210 (2.4%)		2/70 (2.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.