A Single Ascending Dose Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04023994
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 6
• Actual Duration (Months): 11.5
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

Study BP41192 is a randomized, adaptive, placebo-controlled parallel group study to investigate the safety, tolerability, immunogenicity and pharmacokinetics of single-ascending intravenous (IV) doses of RO7126209 in healthy participants. RO7126209 is being developed for the treatment of Alzheimer's Disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimers Disease	Drug: RO7126209; Drug: Placebo	Phase 1

Detailed Description

This study uses a parallel group design, with participants recruited in 5 planned sequential cohorts. Additional cohort(s) may be added if dose escalation stopping criteria are not met after cohort 5. Participants will receive a single IV dose of either RO7126209 or placebo. RO7126209 doses will be administered in ascending order. After the starting dose, subsequent doses will be selected in an adaptive manner during study conduct based on emerging safety, tolerability and PK data.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Single-Center, Randomized, Adaptive, Investigator/Subject Blind, Single Ascending Dose, Placebo-Controlled Phase I Study to Investigate the Safety, Tolerability, Immunogenicity and Pharmacokinetics of Intravenously Administered RO7126209 in Healthy Participants
• Actual Study Start Date: Aug 3, 2019
• Actual Primary Completion Date: Jul 17, 2020
• Actual Study Completion Date: Jul 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.	Drug: Placebo; Participants will be administered a single intravenous dose of matching placebo.
Experimental: RO7126209 (0.1 mg/kg) Healthy volunteers will be administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Drug: RO7126209; Participants will be administered single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.
Experimental: RO7126209 (0.4 mg/kg) Healthy volunteers will be administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Drug: RO7126209; Participants will be administered single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.
Experimental: RO7126209 (1.2 mg/kg) Healthy volunteers will be administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Drug: RO7126209; Participants will be administered single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.
Experimental: RO7126209 (3.6 mg/kg) Healthy volunteers will be administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Drug: RO7126209; Participants will be administered single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.
Experimental: RO7126209 (7.2 mg/kg) Healthy volunteers will be administered a single intravenous dose of RO7126209 (7.2 mg/kg).	Drug: RO7126209; Participants will be administered single-ascending intravenous doses of RO7126209 with at least 2 weeks between each dose level. After the starting dose, the subsequent doses will be selected in an adaptive design. Sentinel dosing will be employed.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adverse Events (AEs) [Up to approximately 9 weeks]

   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.

Secondary Outcome Measures

1. Concentration at the End of Infusion (Cend) of RO7126209 [Day 1]

   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.

2. Area Under the Plasma Concentration Versus Time Curve From Zero to 24 h Postdose (AUC0-24h) of RO7126209 [Days 1 and 2]

   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.

3. Area Under the Plasma Concentration Versus Time Curve From Zero to 168h Postdose (AUC0-168h) of RO7126209 [Days 1, 2, 3, 4, 5 and 8]

   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.

4. Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO7126209 [Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57]

   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.

5. Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) [Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57]

   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.

6. Terminal Rate Constant (Lambda z) of RO7126209 [Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57]

   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.

7. Apparent Terminal Half-Life (T1/2) of RO7126209 [Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57]

   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.

8. Total Body Clearance Calculated as Dose/AUC (CL) of RO7126209 [Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57]

   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.

9. Volume of Distribution at Steady-State (Vss) of RO7126209 [Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57]

   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.

10. Cerebrospinal Fluid (CSF) Concentration of RO7126209 [Day 3 and Day 5]

    RO7126209 CSF concentrations were measured by a specific and validated method. Geometric Mean and Coefficient of Variation data are presented below.

11. Percentage of Participants With Anti-RO7126209 Antibodies (ADAs) [Days 1, 8, 29 and 57]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy status is defined by the absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, ophthalmologic examination, hematology, blood chemistry, coagulation, serology, and urinalysis.

• Body mass index (BMI) of 18-30 kg/m2 inclusive

• During the treatment period and until the final follow up visit, agreement to: (1) Remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of <1% per year, with a partner who is a woman of childbearing potential. (2) With pregnant female partner, remain abstinent or use contraceptive measures such as a condom to avoid exposing the embryo. (3) Refrain from donating sperm from Day 1 of the study until 90 days after last dose.

Exclusion Criteria:

• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study.

• History of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, ophthalmologic, hematological or allergic disease, metabolic disorder, cancer or cirrhosis.

• Any suspicion or history of alcohol abuse and/or suspicion of regular consumption of drug of abuse within the last 5 years.

• Positive result on hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2.

• History or presence of clinically significant ECG abnormalities or cardiovascular disease.

• Clinically-significant abnormalities in laboratory test results.

• Any major illness within one month before the screening examination or any febrile illness within one week prior to screening and up to first dose administration.

• Impaired hepatic function as indicated by screening aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >=1.5 x the upper limit of normal (ULN) or abnormal total bilirubin unless due to Gilbert's disease.

• Any clinically relevant history of hypersensitivity or allergic reactions, either spontaneous or following drug administration, or exposure to foods or environmental agents.

• History of hypersensitivity to biologic agents or any of the excipients in the formulation.

• History of raised intra-cerebral pressure or vertebral joint pathology

• Use of prohibited medication or herbal remedies as described in the section of concomitant medications

• Prior administration of gantenerumab (RO4909832)

• Any vaccination within two months prior to Day 1

• Participation in an investigational drug medicinal product or medical device study within 30 days before screening or within seven times the elimination half-life if known, whichever is longer.

• Participants who regularly smoke more than 5 cigarettes daily or equivalent and are unable or unwilling not to smoke during the in-house period.

• Donation or loss of blood over 500 mL within three months prior to Day 1 and donation of blood for the duration of the study until follow-up.

• Evidence of clinically significant brain magnetic resonance imaging (MRI) findings, including lacunar infarct, territorial infarct or macroscopic hemorrhage, microbleed or area of leptomeningeal hemosiderosis, or deep white matter lesions corresponding to an overall Fazekas score of ≥ 2.

• Claustrophobia, presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that would contraindicate an MRI scan.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA Health Sciences	Raleigh	North Carolina	United States	27612

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 31, 2020

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04023994
• Other Study ID Numbers: BP41192
• First Posted: Jul 18, 2019
• Last Update Posted: Aug 9, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Alzheimer Disease

Study Results

Participant Flow

Recruitment Details	The study was conducted at 1 center in 1 country.
Pre-assignment Detail	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.

Arm/Group Title	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)
Arm/Group Description	In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Period Title: Overall Study
STARTED	10	4	4	6	6	6
COMPLETED	10	3	2	5	6	6
NOT COMPLETED	0	1	2	1	0	0

Baseline Characteristics

Arm/Group Title	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)	Total
Arm/Group Description	In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).	Total of all reporting groups
Overall Participants	10	4	4	6	6	6	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.2 (6.6)	30.8 (5.9)	23.5 (4.5)	24.2 (3.8)	33.0 (5.9)	33.3 (2.6)	29.2 (6.1)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	10 100%	4 100%	4 100%	6 100%	6 100%	6 100%	36 100%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	1 16.7%	2 33.3%	3 8.3%
Not Hispanic or Latino	10 100%	4 100%	4 100%	6 100%	5 83.3%	4 66.7%	33 91.7%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	0 0%	0 0%	0 0%	1 16.7%	0 0%	0 0%	1 2.8%
Asian	2 20%	0 0%	0 0%	0 0%	1 16.7%	0 0%	3 8.3%
Black or African American	3 30%	1 25%	3 75%	3 50%	2 33.3%	1 16.7%	13 36.1%
White	5 50%	2 50%	1 25%	1 16.7%	3 50%	4 66.7%	16 44.4%
Multiple	0 0%	1 25%	0 0%	1 16.7%	0 0%	1 16.7%	3 8.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	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.
Time Frame	Up to approximately 9 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	10	4	4	6	6	6
Number [Percentage of Participants]	80.0 800%	75.0 1875%	50.0 1250%	83.3 1388.3%	100.0 1666.7%	100.0 1666.7%

2. Secondary Outcome

Title	Concentration at the End of Infusion (Cend) of RO7126209
Description	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.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [µg/mL]	1.80 (15.9)	7.93 (21.3)	22.2 (17.6)	85.7 (22.9)	160 (26.5)

3. Secondary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Zero to 24 h Postdose (AUC0-24h) of RO7126209
Description	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.
Time Frame	Days 1 and 2

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hr.µg/mL]	27.1 (23.2)	124 (13.3)	325 (27.1)	1170 (13.3)	2340 (16.5)

4. Secondary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Zero to 168h Postdose (AUC0-168h) of RO7126209
Description	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.
Time Frame	Days 1, 2, 3, 4, 5 and 8

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hr.µg/mL]	78.0 (22.5)	350 (14.2)	807 (28.5)	2940 (11.6)	6190 (13.1)

5. Secondary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO7126209
Description	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.
Time Frame	Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hr.µg/mL]	86.9 (21.9)	402 (14.4)	933 (30.7)	3380 (11.5)	7070 (10.9)

6. Secondary Outcome

Title	Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)
Description	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.
Time Frame	Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hr.µg/mL]	89.1 (21.7)	417 (13.7)	947 (29.3)	3380 (11.5)	7080 (10.9)

7. Secondary Outcome

Title	Terminal Rate Constant (Lambda z) of RO7126209
Description	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.
Time Frame	Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [(1/h)]	0.0103 (19.7)	0.00625 (57.0)	0.00690 (59.0)	0.00409 (19.5)	0.00436 (21.8)

8. Secondary Outcome

Title	Apparent Terminal Half-Life (T1/2) of RO7126209
Description	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.
Time Frame	Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [hr]	67.1 (19.7)	111 (57.0)	100 (59.0)	170 (19.5)	159 (21.8)

9. Secondary Outcome

Title	Total Body Clearance Calculated as Dose/AUC (CL) of RO7126209
Description	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.
Time Frame	Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [mL/hr/kg]	1.14 (21.3)	0.965 (13.8)	1.28 (29.4)	1.07 (10.9)	1.03 (11.1)

10. Secondary Outcome

Title	Volume of Distribution at Steady-State (Vss) of RO7126209
Description	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.
Time Frame	Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	5
Geometric Mean (Geometric Coefficient of Variation) [mL/kg]	88.6 (25.1)	90.3 (26.3)	108 (35.5)	88.7 (22.6)	85.3 (22.8)

11. Secondary Outcome

Title	Cerebrospinal Fluid (CSF) Concentration of RO7126209
Description	RO7126209 CSF concentrations were measured by a specific and validated method. Geometric Mean and Coefficient of Variation data are presented below.
Time Frame	Day 3 and Day 5

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	2	2	3	3	3
Day 3	0.00414 (33.0)	0.0202 (26.5)	0.047 (29.4)	0.105 (40.3)	0.284 (35.9)
Day 5	0.00228 (18.7)	0.0126 (26.1)	0.0274 (22.9)	0.0755 (7.4)	0.151 (9.8)

12. Secondary Outcome

Title	Percentage of Participants With Anti-RO7126209 Antibodies (ADAs)
Description	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.
Time Frame	Days 1, 8, 29 and 57

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	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)
Arm/Group Description	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).	Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
Measure Participants	4	4	6	6	6
Number [Percentage of Participants]	50.0 500%	25.0 625%	66.7 1667.5%	83.3 1388.3%	83.3 1388.3%

Adverse Events

Time Frame	Up to approximately 9 weeks
Arm/Group Title	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)
Arm/Group Description	In Cohorts 1-5, there were ten participants in total who received placebo, two in each cohort.		Healthy volunteers were administered a single intravenous dose of RO7126209 (0.1 mg/kg).		Healthy volunteers were administered a single intravenous dose of RO7126209 (0.4 mg/kg).		Healthy volunteers were administered a single intravenous dose of RO7126209 (1.2 mg/kg).		Healthy volunteers were administered a single intravenous dose of RO7126209 (3.6 mg/kg).		Healthy volunteers were administered a single intravenous dose of RO7126209 (7.2 mg/kg).
All Cause Mortality
	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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious 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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/4 (0%)		0/4 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) 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)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/10 (80%)		3/4 (75%)		2/4 (50%)		5/6 (83.3%)		6/6 (100%)		6/6 (100%)
Gastrointestinal disorders
Nausea	3/10 (30%)	3	0/4 (0%)	0	0/4 (0%)	0	3/6 (50%)	3	2/6 (33.3%)	2	0/6 (0%)	0
Vomiting	2/10 (20%)	2	0/4 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0
General disorders
Chills	0/10 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Crepitations	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Injection site extravasation	0/10 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Infections and infestations
Pharyngitis	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Upper respiratory tract infection	2/10 (20%)	2	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	5/6 (83.3%)	5	6/6 (100%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Back pain	0/10 (0%)	0	3/4 (75%)	3	1/4 (25%)	1	3/6 (50%)	4	1/6 (16.7%)	1	0/6 (0%)	0
Myalgia	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Neck pain	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nervous system disorders
Dizziness	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Headache	5/10 (50%)	6	0/4 (0%)	0	1/4 (25%)	1	5/6 (83.3%)	5	1/6 (16.7%)	1	3/6 (50%)	3
Migraine	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Paraesthesia	1/10 (10%)	2	0/4 (0%)	0	0/4 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/10 (10%)	1	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Vascular disorders
Phlebitis	0/10 (0%)	0	0/4 (0%)	0	0/4 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.