Trial Outcomes & Findings for A Single Ascending Dose Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants (NCT NCT04023994)
NCT ID: NCT04023994
Last Updated: 2021-08-09
Results Overview
An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.
COMPLETED
PHASE1
36 participants
Up to approximately 9 weeks
2021-08-09
Participant Flow
The study was conducted at 1 center in 1 country.
A total of 36 participants were enrolled at 1 site in the US, out of which 26 participants received active treatment while 10 received placebo.
Participant milestones
| Measure |
Placebo
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
10
|
4
|
4
|
6
|
6
|
6
|
|
Overall Study
COMPLETED
|
10
|
3
|
2
|
5
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
2
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Placebo
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
2
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
0
|
0
|
Baseline Characteristics
A Single Ascending Dose Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants
Baseline characteristics by cohort
| Measure |
Placebo
n=10 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
Total
n=36 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
29.2 years
STANDARD_DEVIATION 6.6 • n=39 Participants
|
30.8 years
STANDARD_DEVIATION 5.9 • n=41 Participants
|
23.5 years
STANDARD_DEVIATION 4.5 • n=35 Participants
|
24.2 years
STANDARD_DEVIATION 3.8 • n=31 Participants
|
33.0 years
STANDARD_DEVIATION 5.9 • n=146 Participants
|
33.3 years
STANDARD_DEVIATION 2.6 • n=19 Participants
|
29.2 years
STANDARD_DEVIATION 6.1 • n=147 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=146 Participants
|
0 Participants
n=19 Participants
|
0 Participants
n=147 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
6 Participants
n=31 Participants
|
6 Participants
n=146 Participants
|
6 Participants
n=19 Participants
|
36 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
1 Participants
n=146 Participants
|
2 Participants
n=19 Participants
|
3 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
10 Participants
n=39 Participants
|
4 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
6 Participants
n=31 Participants
|
5 Participants
n=146 Participants
|
4 Participants
n=19 Participants
|
33 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
0 Participants
n=146 Participants
|
0 Participants
n=19 Participants
|
1 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
1 Participants
n=146 Participants
|
0 Participants
n=19 Participants
|
3 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
3 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
3 Participants
n=35 Participants
|
3 Participants
n=31 Participants
|
2 Participants
n=146 Participants
|
1 Participants
n=19 Participants
|
13 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
White
|
5 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
3 Participants
n=146 Participants
|
4 Participants
n=19 Participants
|
16 Participants
n=147 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
0 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
0 Participants
n=146 Participants
|
1 Participants
n=19 Participants
|
3 Participants
n=147 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 9 weeksPopulation: The Safety Population was defined as all participants randomised to study treatment and who received at least one dose of the study treatment, whether prematurely withdrawn from the study or not.
An Adverse Event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An Adverse Event can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as Adverse Events.
Outcome measures
| Measure |
Placebo
n=10 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants With Adverse Events (AEs)
|
80.0 Percentage of Participants
|
75.0 Percentage of Participants
|
50.0 Percentage of Participants
|
83.3 Percentage of Participants
|
100.0 Percentage of Participants
|
100.0 Percentage of Participants
|
SECONDARY outcome
Timeframe: Day 1Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay at specified timepoints. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Concentration at the End of Infusion (Cend) of RO7126209
|
1.80 µg/mL
Geometric Coefficient of Variation 15.9
|
7.93 µg/mL
Geometric Coefficient of Variation 21.3
|
22.2 µg/mL
Geometric Coefficient of Variation 17.6
|
85.7 µg/mL
Geometric Coefficient of Variation 22.9
|
160 µg/mL
Geometric Coefficient of Variation 26.5
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 2Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to 24 h Postdose (AUC0-24h) of RO7126209
|
27.1 hr.µg/mL
Geometric Coefficient of Variation 23.2
|
124 hr.µg/mL
Geometric Coefficient of Variation 13.3
|
325 hr.µg/mL
Geometric Coefficient of Variation 27.1
|
1170 hr.µg/mL
Geometric Coefficient of Variation 13.3
|
2340 hr.µg/mL
Geometric Coefficient of Variation 16.5
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5 and 8Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to 168h Postdose (AUC0-168h) of RO7126209
|
78.0 hr.µg/mL
Geometric Coefficient of Variation 22.5
|
350 hr.µg/mL
Geometric Coefficient of Variation 14.2
|
807 hr.µg/mL
Geometric Coefficient of Variation 28.5
|
2940 hr.µg/mL
Geometric Coefficient of Variation 11.6
|
6190 hr.µg/mL
Geometric Coefficient of Variation 13.1
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO7126209
|
86.9 hr.µg/mL
Geometric Coefficient of Variation 21.9
|
402 hr.µg/mL
Geometric Coefficient of Variation 14.4
|
933 hr.µg/mL
Geometric Coefficient of Variation 30.7
|
3380 hr.µg/mL
Geometric Coefficient of Variation 11.5
|
7070 hr.µg/mL
Geometric Coefficient of Variation 10.9
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
|
89.1 hr.µg/mL
Geometric Coefficient of Variation 21.7
|
417 hr.µg/mL
Geometric Coefficient of Variation 13.7
|
947 hr.µg/mL
Geometric Coefficient of Variation 29.3
|
3380 hr.µg/mL
Geometric Coefficient of Variation 11.5
|
7080 hr.µg/mL
Geometric Coefficient of Variation 10.9
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Terminal Rate Constant (Lambda z) of RO7126209
|
0.0103 (1/h)
Geometric Coefficient of Variation 19.7
|
0.00625 (1/h)
Geometric Coefficient of Variation 57.0
|
0.00690 (1/h)
Geometric Coefficient of Variation 59.0
|
0.00409 (1/h)
Geometric Coefficient of Variation 19.5
|
0.00436 (1/h)
Geometric Coefficient of Variation 21.8
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Apparent Terminal Half-Life (T1/2) of RO7126209
|
67.1 hr
Geometric Coefficient of Variation 19.7
|
111 hr
Geometric Coefficient of Variation 57.0
|
100 hr
Geometric Coefficient of Variation 59.0
|
170 hr
Geometric Coefficient of Variation 19.5
|
159 hr
Geometric Coefficient of Variation 21.8
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Total Body Clearance Calculated as Dose/AUC (CL) of RO7126209
|
1.14 mL/hr/kg
Geometric Coefficient of Variation 21.3
|
0.965 mL/hr/kg
Geometric Coefficient of Variation 13.8
|
1.28 mL/hr/kg
Geometric Coefficient of Variation 29.4
|
1.07 mL/hr/kg
Geometric Coefficient of Variation 10.9
|
1.03 mL/hr/kg
Geometric Coefficient of Variation 11.1
|
—
|
SECONDARY outcome
Timeframe: Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
Plasma concentrations of RO7126209 were measured by a specific and validated assay. Plasma PK parameters of RO7126209 were read directly from the plasma concentration versus time profiles or calculated by using standard non-compartmental methods. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=5 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Volume of Distribution at Steady-State (Vss) of RO7126209
|
88.6 mL/kg
Geometric Coefficient of Variation 25.1
|
90.3 mL/kg
Geometric Coefficient of Variation 26.3
|
108 mL/kg
Geometric Coefficient of Variation 35.5
|
88.7 mL/kg
Geometric Coefficient of Variation 22.6
|
85.3 mL/kg
Geometric Coefficient of Variation 22.8
|
—
|
SECONDARY outcome
Timeframe: Day 3 and Day 5Population: The PK Analysis population was defined as all participants who received active (RO7126209) treatment. Participants were excluded from the PK analysis population if they significantly violated the inclusion or exclusion criteria, deviated significantly from the protocol, or if data were unavailable or incomplete which could have influenced the PK analysis. Data presented below is only for participants included in the actual analysis.
RO7126209 CSF concentrations were measured by a specific and validated method. Geometric Mean and Coefficient of Variation data are presented below.
Outcome measures
| Measure |
Placebo
n=2 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=2 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=3 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=3 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=3 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Cerebrospinal Fluid (CSF) Concentration of RO7126209
Day 5
|
0.00228 µg/mL
Geometric Coefficient of Variation 18.7
|
0.0126 µg/mL
Geometric Coefficient of Variation 26.1
|
0.0274 µg/mL
Geometric Coefficient of Variation 22.9
|
0.0755 µg/mL
Geometric Coefficient of Variation 7.4
|
0.151 µg/mL
Geometric Coefficient of Variation 9.8
|
—
|
|
Cerebrospinal Fluid (CSF) Concentration of RO7126209
Day 3
|
0.00414 µg/mL
Geometric Coefficient of Variation 33.0
|
0.0202 µg/mL
Geometric Coefficient of Variation 26.5
|
0.047 µg/mL
Geometric Coefficient of Variation 29.4
|
0.105 µg/mL
Geometric Coefficient of Variation 40.3
|
0.284 µg/mL
Geometric Coefficient of Variation 35.9
|
—
|
SECONDARY outcome
Timeframe: Days 1, 8, 29 and 57Population: The Immunogenicity population was defined as all participants who had at least one pre-dose or at least one post dose ADA assessment and were included and analysed according to the treatment they actually received. Data presented below is only for participants included in the actual analysis.
The numbers and proportions of Anti-Drug Antibody (ADA) positive participants and ADA negative participants at baseline (baseline prevalence) and after study drug administration (post-baseline incidence during both the treatment and follow-up periods) were summarized per dose group during both the treatment and follow-up period.
Outcome measures
| Measure |
Placebo
n=4 Participants
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=6 Participants
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Percentage of Participants With Anti-RO7126209 Antibodies (ADAs)
|
50.0 Percentage of Participants
|
25.0 Percentage of Participants
|
66.7 Percentage of Participants
|
83.3 Percentage of Participants
|
83.3 Percentage of Participants
|
—
|
Adverse Events
Placebo
RO7126209 (0.1 mg/kg)
RO7126209 (0.4 mg/kg)
RO7126209 (1.2 mg/kg)
RO7126209 (3.6 mg/kg)
RO7126209 (7.2 mg/kg)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=10 participants at risk
In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.
|
RO7126209 (0.1 mg/kg)
n=4 participants at risk
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).
|
RO7126209 (0.4 mg/kg)
n=4 participants at risk
Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).
|
RO7126209 (1.2 mg/kg)
n=6 participants at risk
Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).
|
RO7126209 (3.6 mg/kg)
n=6 participants at risk
Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).
|
RO7126209 (7.2 mg/kg)
n=6 participants at risk
Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
30.0%
3/10 • Number of events 3 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
50.0%
3/6 • Number of events 3 • Up to approximately 9 weeks
|
33.3%
2/6 • Number of events 2 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Gastrointestinal disorders
Vomiting
|
20.0%
2/10 • Number of events 2 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
General disorders
Chills
|
0.00%
0/10 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
General disorders
Crepitations
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
General disorders
Injection site extravasation
|
0.00%
0/10 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
|
Infections and infestations
Pharyngitis
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
2/10 • Number of events 2 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
83.3%
5/6 • Number of events 5 • Up to approximately 9 weeks
|
100.0%
6/6 • Number of events 6 • Up to approximately 9 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/10 • Up to approximately 9 weeks
|
75.0%
3/4 • Number of events 3 • Up to approximately 9 weeks
|
25.0%
1/4 • Number of events 1 • Up to approximately 9 weeks
|
50.0%
3/6 • Number of events 4 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Nervous system disorders
Dizziness
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Nervous system disorders
Headache
|
50.0%
5/10 • Number of events 6 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
25.0%
1/4 • Number of events 1 • Up to approximately 9 weeks
|
83.3%
5/6 • Number of events 5 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
50.0%
3/6 • Number of events 3 • Up to approximately 9 weeks
|
|
Nervous system disorders
Migraine
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Nervous system disorders
Paraesthesia
|
10.0%
1/10 • Number of events 2 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
1/10 • Number of events 1 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
|
Vascular disorders
Phlebitis
|
0.00%
0/10 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/4 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
0.00%
0/6 • Up to approximately 9 weeks
|
16.7%
1/6 • Number of events 1 • Up to approximately 9 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER