CompletedPhase 1Results posted

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

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

Lead sponsor

Hoffmann-La Roche

Asset

Trontinemab

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Age 18-40•Male

Primary endpoint

•Adverse Events (AEs)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDBP41192

NCT IDNCT04023994

Timeline

Milestones

Study first posted2019-07-18actual

Study start2019-08-03actual

Primary completion2020-07-17actual

Study completion2020-07-17actual

Last update posted2021-08-09actual

Results first posted2021-08-09actual

Assets

Drug assets

Trontinemab

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age18 Years

Maximum age40 Years

SexMale

Healthy volunteersAccepted

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.

Endpoints (24)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Fluid / digital biomarkers

Other (unclassified)

Fluid / digital biomarkers

2 endpoints

Secondary/protocol endpoint

Cerebrospinal Fluid (CSF) Concentration of RO7126209

Time frame:Day 3 and Day 5

concentration, descriptive

Secondary/registry result

Cerebrospinal Fluid (CSF) Concentration of RO7126209

Time frame:Day 3 and Day 5

concentration, descriptive

Posted result

Group	Value (geometric_mean), µg/mL	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)Day 3n=2 Participants	0.00414	33.0
Day 5n=2 Participants	0.00228	18.7
RO7126209 (0.4 mg/kg)Day 3n=2 Participants	0.0202	26.5
Day 5n=2 Participants	0.0126	26.1
RO7126209 (1.2 mg/kg)Day 3n=3 Participants	0.047	29.4
Day 5n=3 Participants	0.0274	22.9
RO7126209 (3.6 mg/kg)Day 3n=3 Participants	0.105	40.3
Day 5n=3 Participants	0.0755	7.4
RO7126209 (7.2 mg/kg)Day 3n=3 Participants	0.284	35.9
Day 5n=2 Participants	0.151	9.8

Safety / tolerability / PK

20 endpoints

Primary/protocol endpoint

Percentage of Participants With Adverse Events (AEs)

Time frame:Up to approximately 9 weeks

threshold achievement, event

Primary/registry result

Percentage of Participants With Adverse Events (AEs)

Time frame:Up to approximately 9 weeks

threshold achievement, event

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
Placebon=10 Participants	80.0	-
RO7126209 (0.1 mg/kg)n=4 Participants	75.0	-
RO7126209 (0.4 mg/kg)n=4 Participants	50.0	-
RO7126209 (1.2 mg/kg)n=6 Participants	83.3	-
RO7126209 (3.6 mg/kg)n=6 Participants	100.0	-
RO7126209 (7.2 mg/kg)n=6 Participants	100.0	-

Secondary/protocol endpoint

Concentration at the End of Infusion (Cend) of RO7126209

Time frame:Day 1

concentration, descriptive

Secondary/protocol endpoint

Area Under the Plasma Concentration Versus Time Curve From Zero to 24 h Postdose (AUC0-24h) of RO7126209

Time frame:Days 1 and 2

concentration, descriptive

Secondary/protocol endpoint

Area Under the Plasma Concentration Versus Time Curve From Zero to 168h Postdose (AUC0-168h) of RO7126209

Time frame:Days 1, 2, 3, 4, 5 and 8

concentration, descriptive

Secondary/protocol endpoint

Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Secondary/protocol endpoint

Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Secondary/protocol endpoint

Terminal Rate Constant (Lambda z) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Secondary/protocol endpoint

Apparent Terminal Half-Life (T1/2) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Secondary/protocol endpoint

Total Body Clearance Calculated as Dose/AUC (CL) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Secondary/protocol endpoint

Volume of Distribution at Steady-State (Vss) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Secondary/registry result

Concentration at the End of Infusion (Cend) of RO7126209

Time frame:Day 1

concentration, descriptive

Posted result

Group	Value (geometric_mean), µg/mL	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	1.80	15.9
RO7126209 (0.4 mg/kg)n=4 Participants	7.93	21.3
RO7126209 (1.2 mg/kg)n=6 Participants	22.2	17.6
RO7126209 (3.6 mg/kg)n=6 Participants	85.7	22.9
RO7126209 (7.2 mg/kg)n=5 Participants	160	26.5

Secondary/registry result

Area Under the Plasma Concentration Versus Time Curve From Zero to 24 h Postdose (AUC0-24h) of RO7126209

Time frame:Days 1 and 2

concentration, descriptive

Posted result

Group	Value (geometric_mean), hr.µg/mL	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	27.1	23.2
RO7126209 (0.4 mg/kg)n=4 Participants	124	13.3
RO7126209 (1.2 mg/kg)n=6 Participants	325	27.1
RO7126209 (3.6 mg/kg)n=6 Participants	1170	13.3
RO7126209 (7.2 mg/kg)n=5 Participants	2340	16.5

Secondary/registry result

Area Under the Plasma Concentration Versus Time Curve From Zero to 168h Postdose (AUC0-168h) of RO7126209

Time frame:Days 1, 2, 3, 4, 5 and 8

concentration, descriptive

Posted result

Group	Value (geometric_mean), hr.µg/mL	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	78.0	22.5
RO7126209 (0.4 mg/kg)n=4 Participants	350	14.2
RO7126209 (1.2 mg/kg)n=6 Participants	807	28.5
RO7126209 (3.6 mg/kg)n=6 Participants	2940	11.6
RO7126209 (7.2 mg/kg)n=5 Participants	6190	13.1

Secondary/registry result

Area Under the Plasma Concentration Versus Time Curve From Zero to the Last Measurable Concentration (AUC0-last) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Posted result

Group	Value (geometric_mean), hr.µg/mL	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	86.9	21.9
RO7126209 (0.4 mg/kg)n=4 Participants	402	14.4
RO7126209 (1.2 mg/kg)n=6 Participants	933	30.7
RO7126209 (3.6 mg/kg)n=6 Participants	3380	11.5
RO7126209 (7.2 mg/kg)n=5 Participants	7070	10.9

Secondary/registry result

Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf)

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Posted result

Group	Value (geometric_mean), hr.µg/mL	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	89.1	21.7
RO7126209 (0.4 mg/kg)n=4 Participants	417	13.7
RO7126209 (1.2 mg/kg)n=6 Participants	947	29.3
RO7126209 (3.6 mg/kg)n=6 Participants	3380	11.5
RO7126209 (7.2 mg/kg)n=5 Participants	7080	10.9

Secondary/registry result

Terminal Rate Constant (Lambda z) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Posted result

Group	Value (geometric_mean), (1/h)	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	0.0103	19.7
RO7126209 (0.4 mg/kg)n=4 Participants	0.00625	57.0
RO7126209 (1.2 mg/kg)n=6 Participants	0.00690	59.0
RO7126209 (3.6 mg/kg)n=6 Participants	0.00409	19.5
RO7126209 (7.2 mg/kg)n=5 Participants	0.00436	21.8

Secondary/registry result

Apparent Terminal Half-Life (T1/2) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Posted result

Group	Value (geometric_mean), hr	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	67.1	19.7
RO7126209 (0.4 mg/kg)n=4 Participants	111	57.0
RO7126209 (1.2 mg/kg)n=6 Participants	100	59.0
RO7126209 (3.6 mg/kg)n=6 Participants	170	19.5
RO7126209 (7.2 mg/kg)n=5 Participants	159	21.8

Secondary/registry result

Total Body Clearance Calculated as Dose/AUC (CL) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Posted result

Group	Value (geometric_mean), mL/hr/kg	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	1.14	21.3
RO7126209 (0.4 mg/kg)n=4 Participants	0.965	13.8
RO7126209 (1.2 mg/kg)n=6 Participants	1.28	29.4
RO7126209 (3.6 mg/kg)n=6 Participants	1.07	10.9
RO7126209 (7.2 mg/kg)n=5 Participants	1.03	11.1

Secondary/registry result

Volume of Distribution at Steady-State (Vss) of RO7126209

Time frame:Days 1, 2, 3, 4, 5, 8, 10, 15, 22, 29, 43 and 57

concentration, descriptive

Posted result

Group	Value (geometric_mean), mL/kg	Geometric coefficient of variation
RO7126209 (0.1 mg/kg)n=4 Participants	88.6	25.1
RO7126209 (0.4 mg/kg)n=4 Participants	90.3	26.3
RO7126209 (1.2 mg/kg)n=6 Participants	108	35.5
RO7126209 (3.6 mg/kg)n=6 Participants	88.7	22.6
RO7126209 (7.2 mg/kg)n=5 Participants	85.3	22.8

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Percentage of Participants With Anti-RO7126209 Antibodies (ADAs)

Time frame:Days 1, 8, 29 and 57

threshold achievement, improvement

Secondary/registry result/low confidence

Percentage of Participants With Anti-RO7126209 Antibodies (ADAs)

Time frame:Days 1, 8, 29 and 57

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	Reported bounds
RO7126209 (0.1 mg/kg)n=4 Participants	50.0	-
RO7126209 (0.4 mg/kg)n=4 Participants	25.0	-
RO7126209 (1.2 mg/kg)n=6 Participants	66.7	-
RO7126209 (3.6 mg/kg)n=6 Participants	83.3	-
RO7126209 (7.2 mg/kg)n=6 Participants	83.3	-

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Muliaditan M, van Steeg TJ, Avery LB, Sun W, Hammond TR, Hijdra D, Choi SL, Pillai N, Leksa NC, Mavroudis PD. Translational minimal physiologically based pharmacokinetic model for transferrin receptor-mediated brain delivery of antibodies. MAbs. 2025 Dec;17(1):2515414. doi: 10.1080/19420862.2025.2515414. Epub 2025 Jun 26.
PMID40568753via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.