Trial Outcomes & Findings for Safety, Tolerability and PK of Repeat Administration of Intravenous ETI-204 in Adult Volunteers (NCT NCT01932242)
NCT ID: NCT01932242
Last Updated: 2019-05-14
Results Overview
Safety was assessed for all subjects in the safety population by collecting and monitoring vital signs, laboratory tests, ECGs, physical examinations, skin assessments, infusion site assessments and adverse events.
COMPLETED
PHASE1
70 participants
Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm.
2019-05-14
Participant Flow
Participant milestones
| Measure |
Sequence A
16 mg/kg ETI-204 IV on Days 1 and 14 and Placebo on Day 120
ETI-204: Monoclonal Antibody
Placebo: Placebo for ETI-204
|
Sequence B
16 mg/kg ETI-204 IV on Days 1 and 120 and Placebo on Day 14
ETI-204: Monoclonal Antibody
Placebo: Placebo for ETI-204
|
|---|---|---|
|
Overall Study
STARTED
|
35
|
35
|
|
Overall Study
COMPLETED
|
30
|
30
|
|
Overall Study
NOT COMPLETED
|
5
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety, Tolerability and PK of Repeat Administration of Intravenous ETI-204 in Adult Volunteers
Baseline characteristics by cohort
| Measure |
Sequence A
n=35 Participants
16 mg/kg ETI-204 IV on Days 1 and 14 and Placebo on Day 120
ETI-204: Monoclonal Antibody
Placebo: Placebo for ETI-204
|
Sequence B
n=35 Participants
16 mg/kg ETI-204 IV on Days 1 and 120 and Placebo on Day 14
ETI-204: Monoclonal Antibody
Placebo: Placebo for ETI-204
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
43.0 years
STANDARD_DEVIATION 14.71 • n=93 Participants
|
43.3 years
STANDARD_DEVIATION 16.76 • n=4 Participants
|
43.1 years
STANDARD_DEVIATION 15.65 • n=27 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
26 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
44 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=93 Participants
|
33 Participants
n=4 Participants
|
66 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
45 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Body Weight
|
83.19 kg
STANDARD_DEVIATION 16.452 • n=93 Participants
|
80.55 kg
STANDARD_DEVIATION 16.886 • n=4 Participants
|
81.87 kg
STANDARD_DEVIATION 16.602 • n=27 Participants
|
|
Height
|
171.82 cm
STANDARD_DEVIATION 10.623 • n=93 Participants
|
172.46 cm
STANDARD_DEVIATION 8.520 • n=4 Participants
|
172.14 cm
STANDARD_DEVIATION 9.564 • n=27 Participants
|
|
BMI
|
28.23 kg/m2
STANDARD_DEVIATION 5.608 • n=93 Participants
|
27.06 kg/m2
STANDARD_DEVIATION 5.275 • n=4 Participants
|
27.65 kg/m2
STANDARD_DEVIATION 5.437 • n=27 Participants
|
PRIMARY outcome
Timeframe: Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm.Population: The safety population consisted of all subjects who received at least a partial dose of ETI 204 or placebo, whether prematurely withdrawn from the study or not
Safety was assessed for all subjects in the safety population by collecting and monitoring vital signs, laboratory tests, ECGs, physical examinations, skin assessments, infusion site assessments and adverse events.
Outcome measures
| Measure |
Sequence A
n=35 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=35 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Number of Participants Who Experienced Adverse Events
|
30 Participants
|
31 Participants
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: One subject in Sequence A was prematurely discontinued from the study by the investigator after the 1st dose of ETI-204 because of AEs. This subject did not receive the 2nd dose of ETI-204 on Day 14 and therefore all PK parameters from this subject were excluded from descriptive statistics.
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.The PK parameter, Cmax, was derived from ETI-204 serum concentrations by sequence group and treatment period for the PK analysis population. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=34 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=35 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Maximum Observed Plasma Concentration of ETI-204 (Cmax) After a Dose of 16 mg/kg on Day 1(Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
506 µg/mL
Standard Deviation 102
|
384 µg/mL
Standard Deviation 103
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: Four subjects in Sequence B were excluded because the subjects did not receive the 2nd dose of ETI-204 16 m/kg on Day 120 (one due to AEs after the 1st dose, one withdrew consent due to conflict with work, one was lost to follow-up on Day 43, and one was withdrawn by the investigator due to protocol violation (positive drug screen on Day 120).
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=31 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Maximum Observed Plasma Concentration of ETI-204 (Cmax) After a Dose of 16 mg/kg on Day 120 (Sequence B)
|
—
|
402 µg/mL
Standard Deviation 134
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: One subject in Sequence A was prematurely discontinued from the study by the investigator afte the 1st dose of ETI-204 because of AEs. This subject did not receive the 2nd dose of ETI-204 on Day 14 and therefore all PK parameters from this subject were excluded from descriptive statistics.
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.The PK parameter, Tmax, was derived from ETI-204 serum concentrations by sequence group and treatment period for the PK analysis population. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=34 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=35 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) After a Dose of 16 mg/kg on Day 1(Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
13.1 days
Interval 0.125 to 14.0
|
0.125 days
Interval 0.0625 to 1.0
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: Four subjects in Sequence B were excluded because the subjects did not receive the 2nd dose of ETI-204 16 m/kg on Day 120 (one due to AEs after the 1st dose, one withdrew consent due to conflict with work, one was lost to follow-up on Day 43, and one was withdrawn by the investigator due to protocol violation (positive drug screen on Day 120).
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=31 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) After a Dose of 16 mg/kg on Day 120 (Sequence B)
|
—
|
0.0743 days
Interval 0.0618 to 1.0
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: PK parameters for 1 subject in Sequence A were excluded because the subject was discontinued after the 1st dose of ETI-204 because of AEs and did not receive the 2nd dose. 2 subjects in Sequence A and 1 subject in Sequence B (Day 1) were missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=32 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
10,200 µg.day/mL
Standard Deviation 2,500
|
4550 µg.day/mL
Standard Deviation 1220
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: 4 subjects in Sequence B were excluded because the subjects did not receive the 2nd dose of ETI-204 on Day 120 (1 due to AEs after 1st dose, 1 withdrew consent , 1 lost to follow-up, 1 protocol violation). 1 subjects in Sequence B was missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=30 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)
|
—
|
4300 µg.day/mL
Standard Deviation 1010
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: PK parameters for 1 subject in Sequence A were excluded because the subject did not rec a 2nd dose of ETI-204 due to AEs after the 1st dose. 2 subjects in Sequence A were missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported. AUC0-191days was not calculated for Sequence B.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=32 Participants
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
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to 191 Days (AUC0-191days) After a Dose of 16 mg/kg ETI-204 on Days 1 and 14 (Sequence A)
|
10,300 µg.day/mL
Standard Deviation 2480
|
—
|
SECONDARY outcome
Timeframe: On Day 1 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: One subjects in Sequence B was missing the final 3 or more scheduled samples (subject withdrew from the study on Day 8 due to conflict with work schedule) and therefore AUC and lamda z-based parameters were not reported. AUC0-120days was not calculated for Sequence A.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to 120 Days (AUC0-120days) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B)
|
—
|
4560 µg.day/mL
Standard Deviation 1220
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: PK parameters for 1 subject in Sequence A were excluded because the subject was discontinued after the 1st dose of ETI-204 because of AEs and did not receive the 2nd dose. 2 subjects in Sequence A and 1 subject in Sequence B were missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=32 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
10,300 µg.day/mL
Standard Deviation 2530
|
4690 µg.day/mL
Standard Deviation 1370
|
SECONDARY outcome
Timeframe: On Day 120 prepose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: 4 subjects in Sequence B were excluded because they did not receive the 2nd dose of ETI-204 on Day 120. For 4 subjects in Sequence B the AUC and lambda z-based parameters were excluded from descriptive statistics for Day 120 (1 for missing the final 3 or more scheduled samples, 3 because the t1/2 values were \>50% of the 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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=27 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)
|
—
|
4400 µg.day/mL
Standard Deviation 796
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: PK parameters for 1 subject in Sequence A were excluded because the subject was discontinued after the 1st dose of ETI-204 because of AEs and did not receive the 2nd dose. 2 subjects in Sequence A and 1 subject in Sequence B were missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=32 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Terminal Half-life (t1/2) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
22.8 days
Standard Deviation 5.82
|
21.5 days
Standard Deviation 6.73
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: 4 subjects in Sequence B were excluded because they did not receive the 2nd dose of ETI-204 on Day 120. For 4 subjects in Sequence B the AUC and lambda z-based parameters were excluded from descriptive statistics for Day 120 (1 for missing the final 3 or more scheduled samples, 3 because the t1/2 values were \>50% of the 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.The PK parameter, Cmax, was derived from ETI-204 serum concentrations by sequence group and treatment period for the PK analysis population. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=27 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Terminal Half-life (t1/2) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)
|
—
|
18.6 days
Standard Deviation 3.43
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: PK parameters for 1 subject in Sequence A were excluded because the subject was discontinued after the1st dose of ETI-204 because of AEs and did not receive the 2nd dose. 2 subjects in Sequence A and 1 subject in Sequence B were missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=32 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Systemic Clearance (CL) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
0.274 Liters/day
Standard Deviation 0.0862
|
0.300 Liters/day
Standard Deviation 0.104
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: 4 subjects in Sequence B were excluded because they did not receive the 2nd dose of ETI-204 on Day 120. For 4 subjects in Sequence B the AUC and lambda z-based parameters were excluded from descriptive statistics for Day 120 (1 for missing the final 3 or more scheduled samples, 3 because the t1/2 values were \>50% of the 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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=27 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Systemic Clearance (CL) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)
|
—
|
0.313 Liters/day
Standard Deviation 0.0760
|
SECONDARY outcome
Timeframe: On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: PK parameters for 1 subject in Sequence A were excluded because the subject was discontinued after the 1st dose of ETI-204 because of AEs and did not receive the 2nd dose. 2 subjects in Sequence A and 1 subject in Sequence B were missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
n=32 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Volume of Distribution (Vd) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)
|
8.69 Liters
Standard Deviation 2.65
|
8.75 Liters
Standard Deviation 2.09
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: 4 subjects in Sequence B were excluded because they did not receive the 2nd dose of ETI-204 on Day 120. For 4 subjects in Sequence B the AUC and lambda z-based parameters were excluded from descriptive statistics for Day 120 (1 for missing the final 3 or more scheduled samples, 3 because the t1/2 values were \>50% of the 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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=27 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Volume of Distribution (Vd) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)
|
—
|
8.33 Liters
Standard Deviation 2.39
|
SECONDARY outcome
Timeframe: On Day 1 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: One subject in Sequence B was missing the final 3 or more scheduled samples and therefore AUC and lambda z-based parameters were not reported. Vdss was not reported for Sequence A.
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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=34 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Volume of Distribution at Steady State (Vdss) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B)
|
—
|
7.20 Liters
Standard Deviation 1.49
|
SECONDARY outcome
Timeframe: On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.Population: 4 subjects in Sequence B were excluded because they did not receive the 2nd dose of ETI-204 on Day 120. For 4 subjects in Sequence B the AUC and lambda z-based parameters were excluded from descriptive statistics for Day 120 (1 for missing the final 3 or more scheduled samples, 3 because the t1/2 values were \>50% of the 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. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.
Outcome measures
| Measure |
Sequence A
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=27 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Volume of Distribution at Steady State (Vdss) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)
|
—
|
7.01 Liters
Standard Deviation 2.32
|
SECONDARY outcome
Timeframe: On Days 1,14, and 120 predose and on Days 8, 43, 85, 128, 163, and 191Serum 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 |
Sequence A
n=35 Participants
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=35 Participants
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Number of Participants With Anti-ETI-204 Antibodies
|
3 Participants
|
1 Participants
|
Adverse Events
Sequence A
Sequence B
Serious adverse events
| Measure |
Sequence A
n=35 participants at risk
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=35 participants at risk
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.00%
0/35 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
Other adverse events
| Measure |
Sequence A
n=35 participants at risk
ETI-204 on Days 1 and 14 and placebo on Day 120
|
Sequence B
n=35 participants at risk
ETI-204 on Days 1 and 120 and placebo on Day 14
|
|---|---|---|
|
Nervous system disorders
Somnolence
|
28.6%
10/35 • Number of events 19 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
28.6%
10/35 • Number of events 16 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Infections and infestations
Upper respiratory tract infection
|
17.1%
6/35 • Number of events 6 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
31.4%
11/35 • Number of events 11 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
17.1%
6/35 • Number of events 6 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
11.4%
4/35 • Number of events 6 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
General disorders
Infusion site swelling
|
8.6%
3/35 • Number of events 3 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
11.4%
4/35 • Number of events 4 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Nervous system disorders
Headache
|
8.6%
3/35 • Number of events 4 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
8.6%
3/35 • Number of events 3 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
General disorders
Infusion site erythema
|
11.4%
4/35 • Number of events 4 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
5.7%
2/35 • Number of events 3 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
General disorders
Infusion site pain
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Nervous system disorders
Dizziness
|
5.7%
2/35 • Number of events 3 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Gastrointestinal disorders
Nausea
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
5.7%
2/35 • Number of events 3 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Gastrointestinal disorders
Diarrhoea
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Vascular disorders
Phlebitis superficial
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.7%
2/35 • Number of events 2 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
2.9%
1/35 • Number of events 1 • Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm
|
Additional Information
Senior Director of Regulatory
Elusys Therapeutics, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee The data generated in this clinical study are the exclusive property of the sponsor and are confidential. Written approval from the sponsor is required prior to disclosing any information related to this clinical study.
- Publication restrictions are in place
Restriction type: OTHER