Trial Outcomes & Findings for Safety, Tolerability, and PK of a Single Intravenous Dose of ETI-204 in Adult Volunteers (NCT NCT01929226)

NCT ID: NCT01929226

Last Updated: 2019-04-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 280 participants
• Primary outcome timeframe: 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.
• Results posted on: 2019-04-08

Participant Flow

Participant milestones

Measure	ETI-204 Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Placebo Intravenously (IV), single dose Placebo: Placebo comparator
Overall Study STARTED	210	70
Overall Study COMPLETED	205	69
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Measure	ETI-204 Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Placebo Intravenously (IV), single dose Placebo: Placebo comparator
Overall Study Lost to Follow-up	4	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	ETI-204 n=210 Participants Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Placebo n=70 Participants Intravenously (IV), single dose Placebo: Placebo comparator	Total n=280 Participants Total of all reporting groups
Age, Continuous	42.4 years STANDARD_DEVIATION 15.59 • n=5 Participants	41.5 years STANDARD_DEVIATION 13.90 • n=7 Participants	42.2 years STANDARD_DEVIATION 15.17 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants	32 Participants n=7 Participants	136 Participants n=5 Participants
Sex: Female, Male Male	106 Participants n=5 Participants	38 Participants n=7 Participants	144 Participants n=5 Participants
Region of Enrollment United States	210 participants n=5 Participants	70 participants n=7 Participants	280 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Population: All randomized participants who received study drug.

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.

Outcome measures

Measure	ETI-204 n=210 Participants 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.	Placebo n=70 Participants 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.
Number of Participants Who Experienced Adverse Events	88 Participants	27 Participants

SECONDARY outcome

Timeframe: 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.

Population: 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).

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.

Outcome measures

Measure	ETI-204 n=202 Participants 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.	Placebo 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.
Maximum Observed Plasma Concentration of ETI-204 (Cmax)	400 µg/mL Standard Deviation 91.2	—

SECONDARY outcome

Timeframe: 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.

Population: 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).

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.

Outcome measures

Measure	ETI-204 n=202 Participants 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.	Placebo 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.
Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)	0.0782 days Interval 0.0674 to 1.01	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	ETI-204 n=199 Participants 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.	Placebo 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.
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last)	4770 µg.day/mL Standard Deviation 1160	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	ETI-204 n=191 Participants 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.	Placebo 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.
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf)	5170 µg.day/mL Standard Deviation 1360	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	ETI-204 n=193 Participants 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.	Placebo 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.
Terminal Half-life (t1/2)	20.2 days Standard Deviation 5.26	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	ETI-204 n=191 Participants 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.	Placebo 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.
Systemic Clearance (CL)	0.270 Liters/day Standard Deviation 0.0886	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	ETI-204 n=191 Participants 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.	Placebo 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.
Volume of Distribution (Vd)	7.41 Liters Standard Deviation 1.90	—

SECONDARY outcome

Timeframe: 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.

Population: 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.

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.

Outcome measures

Measure	ETI-204 n=191 Participants 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.	Placebo 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.
Volume of Distribution at Steady State (Vss)	6.34 Liters Standard Deviation 1.55	—

SECONDARY outcome

Timeframe: On Day 1 prior to the start of infusion and on Days 8, 43, and 71.

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

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.

Outcome measures

Measure	ETI-204 n=210 Participants 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.	Placebo n=70 Participants 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.
Number of Participants With Anti-ETI-204 Antibodies	2 Participants	0 Participants

Adverse Events

ETI-204

Serious events: 0 serious events

Other events: 52 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Measure	ETI-204 n=210 participants at risk Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Placebo n=70 participants at risk Intravenously (IV), single dose Placebo: Placebo comparator
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/210 • 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.	1.4% 1/70 • Number of events 1 • 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.

Other adverse events

Measure	ETI-204 n=210 participants at risk Intravenously (IV), single dose ETI-204: Monoclonal Antibody	Placebo n=70 participants at risk Intravenously (IV), single dose Placebo: Placebo comparator
Gastrointestinal disorders Diarrhoea	0.00% 0/210 • 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.	2.9% 2/70 • 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.
Gastrointestinal disorders Nausea	2.4% 5/210 • 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.	2.9% 2/70 • 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.
General disorders Infusion site erythema	0.00% 0/210 • 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.	2.9% 2/70 • 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.
General disorders Pain	1.4% 3/210 • 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.	2.9% 2/70 • 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.
General disorders Vessel puncture site bruise	3.3% 7/210 • 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.	1.4% 1/70 • 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.
Infections and infestations Upper respiratory tract infection	2.4% 5/210 • 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.	2.9% 2/70 • 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.
Infections and infestations Urinary tract infection	0.00% 0/210 • 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.	2.9% 2/70 • 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.
Musculoskeletal and connective tissue disorders Back pain	0.48% 1/210 • 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.	4.3% 3/70 • 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.
Nervous system disorders Headache	10.0% 21/210 • 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.	5.7% 4/70 • 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.
Respiratory, thoracic and mediastinal disorders Cough	2.9% 6/210 • 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.	0.00% 0/70 • 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.
Skin and subcutaneous tissue disorders Pruritus	4.8% 10/210 • 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.	1.4% 1/70 • 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.
Skin and subcutaneous tissue disorders Rash	2.4% 5/210 • 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.	2.9% 2/70 • 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.

Additional Information

Senior Director of Regulatory

Elusys Therapeutics, Inc.

Phone: 973-808-0222

Email: cdillon@elusys.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place