Study on the efficacy of Trontinemab compared to a placebo in individuals with early symptoms of Alzheimer's disease.
Résumé de l'étude
Clinical study of Trontinemab in early Alzheimer's disease: Summary 1. Background & Objective: Alzheimer's disease is caused by amyloid plaques. The investigational drug Trontinemab aims to remove these plaques and treat early symptoms. The goal of this double-blind, placebo-controlled study is to compare the efficacy and safety of Trontinemab against a placebo in individuals in the early symptomatic stage. 2. Eligibility: Suitable participants (ages 50–90) have mild, daily life-impacting Alzheimer's symptoms, with confirmed amyloid plaques (PET/lumbar puncture). Maximum weight is 150 kg, and a study partner is required. Exclusion criteria include other brain diseases, lack of MRI capability, wet age-related macular degeneration, or pregnancy/breastfeeding. 3. Study procedure and duration: After a maximum of 8 weeks of screening, participants will be randomly assigned to Trontinemab or placebo. Treatment will be administered as an intravenous infusion, initially approximately every 4 weeks. The study is double-blind. Participation lasts about 1 year and 7 months in total. Participants can withdraw at any time. An extension of the study with Trontinemab is possible. 4. Primary objectives: The primary objective is to measure efficacy up to week 72 based on changes in memory, thinking, and daily functioning (using questionnaires). Cognitive abilities, amyloid/Tau proteins, biomarkers, and the number and severity of side effects will also be recorded. 5. Opportunities and risks: Benefits: Possible improvement of the disease; important data for future treatments. Risks: Safety and efficacy are not yet fully known. Possible side effects include infusion-related reactions and particularly inflammation/bleeding in the brain (ARIA abnormalities). The investigational drug may be harmful to unborn children.
(BASEC)
Intervention étudiée
The intervention under investigation is a multicenter, randomized, double-blind, placebo-controlled parallel-group Phase III study assessing the efficacy and safety (protocols WN45443, also known as TRONTIER 1, and WN45447, also known as TRONTIER 2). The study aims to evaluate the efficacy and safety of an investigational product in participants with early symptomatic Alzheimer's disease (AD), ranging from mild cognitive impairment (MCI) to mild dementia due to AD.
Investigational drug
The primary investigational medicinal product (IMP) is Trontinemab.
• Drug name: Trontinemab (also known by the code number RO7126209).
• Mechanism of action: Trontinemab is a recombinant (2+1) bispecific monoclonal antibody (mAb) construct that targets both human Aβ peptide and human transferrin receptor 1 (TfR1). It combines an anti-amyloid antibody (Gantenerumab) with a special module known as Brainshuttle™. The Brainshuttle™ module enables active penetration of the blood-brain barrier to deliver significantly higher concentrations of the antibody to the central nervous system (CNS). Trontinemab works by preventing, blocking, and/or reducing the accumulation of beta-amyloid plaques in the brain.
• Treatment groups: Participants will be randomly assigned to receive either Trontinemab or a placebo. The investigational product or placebo will be administered via intravenous (i.v.) infusion. The target dose is 3.6 mg/kg.
Additional drugs (diagnostics)
The study also includes the use of special radioactive diagnostics for imaging procedures:
• Amyloid positron emission tomography (PET) imaging: Used to confirm amyloid-beta (Aβ) levels for eligibility and measure longitudinal changes. The following radiopharmaceutical ligands are approved as tracers:
o [18F]Flutemetamol (trade name: Vizamyl®).
o [18F]Florbetaben (trade name: Neuraceq®).
o Not used in Switzerland but mentioned in the protocol: [18F]Florbetapir (trade name: Amyvid®).
• Tau-PET imaging: not performed in Switzerland, hence [18F]MK-6240 is not used.
(BASEC)
Maladie en cours d'investigation
Mild cognitive impairment (MCI) to mild dementia due to Alzheimer's disease (AD)
(BASEC)
- Evidence of a pathological process of Alzheimer's disease, confirmed by visual assessment of an amyloid PET scan by the central PET laboratory. A CSF ratio of tau181/Aβ42 may be used as an alternative option if no amyloid PET is available. - MMSE score at screening ≥ 22 and CDR-GS of 0.5 or 1.0. - Participant and/or informant-reported history of cognitive decline with gradual onset and progression in the last year prior to screening, as documented in the diagnostic review form. (BASEC)
Critères d'exclusion
Any evidence of another disease than Alzheimer's disease that could impair cognition, including but not limited to frontotemporal dementia, dementia with Lewy bodies, vascular dementia, Parkinson's disease, corticobasal syndrome, Creutzfeldt-Jakob disease, progressive supranuclear palsy, frontotemporal lobar degeneration (except frontotemporal dementia), Huntington's disease, normal pressure hydrocephalus, seizure disorders, delirium, or hypoxia. History or presence of clinically significant cerebrovascular disease (e.g., intracranial or cerebral vascular malformations, aneurysm, intracranial macrobleeding). In the case of a small, isolated developmental venous anomaly, the judgment of the principal investigator applies. History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder. (BASEC)
Lieu de l’étude
Berne, Genève, Lausanne, Lugano
(BASEC)
Sponsor
F. Hoffmann-La Roche AG
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Clinical trials
+41 61 715 44 85
switzerland.clinical-research@clutterroche.comClinical trials
(BASEC)
Informations générales
Hoffmann-La Roche
888-662-6728
global-roche-genentech-trials@gene.com(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Genève
(BASEC)
Date d'approbation du comité d'éthique
23.02.2026
(BASEC)
Identifiant de l'essai ICTRP
NCT07170150 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP EFFICACY AND SAFETY STUDY OF TRONTINEMAB IN PARTICIPANTS WITH EARLY SYMPTOMATIC ALZHEIMER’S DISEASE (MCI TO MILD DEMENTIA DUE TO AD) (BASEC)
Titre académique
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Study of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (MCI to Mild Dementia Due to AD) (ICTRP)
Titre public
A Clinical Trial of Trontinemab in Participants With Early Symptomatic Alzheimer's Disease (ICTRP)
Maladie en cours d'investigation
Alzheimers Disease (ICTRP)
Intervention étudiée
Drug: TrontinemabOther: Placebo (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Willingness and ability to complete all aspects of the study (including MRI,
clinical genotyping, and PET imaging or CSF as applicable) for the duration of the
study. The participant should be capable of completing assessments either alone or
with the help of the study partner
- Adequate visual and auditory acuity, in the investigator's judgment, sufficient to
perform the neuropsychological testing (eyewear and hearing aids are permitted)
- Evidence of AD pathological process, as confirmed on amyloid PET scan. A CSF
tau181/A42 ratio may be used as an alternative option if amyloid PET is not
available
- Probable AD dementia or MCI due to AD, also known as an Alzheimer's clinical
syndrome clinical Stage 3 or Stage 4
- Screening MMSE score = 22 and CDR-GS of 0.5 or 1.0
- Participant- and/or Informant-reported history of cognitive decline with gradual
onset and progression over the last 1 year before screening
- A Repeatable Battery for the Assessment of Neuropsychological Status Delayed Memory
Index (RBANS DMI) score of 85 or order
- Availability of a "study partner" as defined by the protocol
Exclusion Criteria:
- Any evidence of a condition other than AD that may affect cognition
- History or presence of clinically significant cerebrovascular disease
- History of severe, clinically significant (persistent neurologic deficit or
structural brain damage) central nervous system (CNS) trauma
- History or presence of clinically significant intracranial mass
- MRI evidence of significant cerebral abnormalities or inability to tolerate MRI
procedures or contraindication to MRI
- Any other medical conditions (e.g., cardiovascular, hepatic, renal disease) which
are not stable and adequately controlled or which in the opinion of the investigator
could affect the participant's safety in the study or interfere with the study
assessments
- History of malignancy with the following exceptions: if considered to be cured
malignancies with a negligible risk of metastasis or death (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Change from baseline to Week 72 in Clinical Dementia Rating, Sum of Boxes (CDR-SB) (ICTRP)
Change from baseline through Week 72 in Alzheimer's Disease Assessment Scale-Cognition 13 (ADAS-Cog-13);Change from baseline through Week 72 in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) total score and instrumental score;Change from baseline through Week 72 in Integrated Alzheimer's Disease Rating Scale (iADRS);Change from baseline through Week 72 in Mini-Mental State Examination (MMSE);Change from baseline in CDR-SB;Time to increase in Clinical Dementia Rating, Global Score (CDR-GS);Percentage of participants with adverse events (AEs);Percentage of participants with amyloid-related imaging abnormalities (ARIA) magnetic resonance imaging (MRI) findings;Percentage of participants with infusion-related reactions (IRR);Percentage of participants with anti-drug antibodies (ADAs) to trontinemab;Change from baseline through Week 72 in brain amyloid load as measured by amyloid positron emission tomography (PET) scan;Change from baseline to Week 72 in brain tau load as measured by tau PET scan in a subset of participants;Change from baseline through Week 72 in cerebrospinal fluid (CSF) biomarkers of disease p-tau181, neurogranin, A�42 in a subset of participants;Change from baseline through Week 72 in blood biomarkers p-tau217, glial fibrillar acidic protein (GFAP) (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Clinical TrialsReference Study ID Number: WN45447 https://forpatients.roche.com/, global-roche-genentech-trials@gene.com, 888-662-6728, Hoffmann-La Roche (ICTRP)
ID secondaires
WN45447 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT07170150 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
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