Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer's Disease Caused by a Genetic Mutation

A Phase II/III randomized, double-blind, placebo-controlled multi-center study of 2 potential disease modifying therapies in individuals at risk for and with dominantly inherited Alzheimer's disease (ADAD)

Status

Active, not recruiting

Phases

Phase 2Phase 3

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2013-000307-17-IT

Enrollment

210

Registered

2013-09-30

Start date

2014-04-30

Completion date

Unknown

Last updated

2024-12-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Autosomal Dominant Alzheimer's disease MedDRA version: 16.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852

Interventions

Product Name: Solanezumab Product Code: LY2062430 Pharmaceutical Form: Solution for infusion INN or Proposed INN: Solanezumab CAS Number: 955085-14-0 Current Sponsor code: LY2062430 Other descriptive

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Subjects must meet ALL inclusion criteria: 1.Know they have an AD-causing mutation or be unaware of their genetic status and have a 50% chance of having an AD-causing mutation (e.g. parent or sibling with known AD-causing mutation) 2.Are within -15 to + 10 years of the parental age of symptom onset 3. CDR 0-1 inclusive 4. Are able to undergo MRI, LP, PET, and complete all study related testing and evaluations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 189 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 21

Exclusion criteria

Exclusion criteria: Subjects will be excluded if they have a major or unstable illness or are unable to complete all study related testing. Exclusions include implanted metal that cannot be removed for MR scanning, required anticoagulation and pregnancy. Baseline MRI scan indicative of any other significant abnormality, including more than 4 definite micro hemorrhages. Clinically relevant abnormalities in chemistry, hematology or coagulation studies.

Design outcomes

Primary

Measure	Time frame
Main Objective: 1. Assess safety and tolerability of gantenerumab and solanezumab in individuals who have mutations causing dominantly inherited Alzheimer’s disease. 2. Assess biological efficacy/target engagement of gantenerumab and solanezumab in individuals who have mutations causing dominantly inherited Alzheimer’s disease as measured by the primary biomarker measure for each drug. Primary endpoints are specified for each drug based on mechanism of action. Depending on proposed mechanism of action, the primary biomarker endpoint will be either 1) change in amyloid deposition as measured by [11C]PiB-PET composite standardized uptake value ratio (C-SUVR, average of precuneus, caudate, gyrus rectus, occipital cortex, parietal cortex, prefrontal cortex and temporal cortex) or, 2) changes in free and total amyloid beta (Aß) isoforms in CSF.;Secondary Objective: Secondary study endpoints will include: 1) Change in amyloid deposition as measured by [11C]PiB-PET C-SUVR (used as a secondary outcome measure when not the primary outcome measure). 2) Change in CSF amyloid-beta peptide concentrations (used as a secondary outcome measure when not the primary outcome measure). 3) Change of CSF biomarkers tau and ptau181 values compared between subjects on active drug (gantenerumab or solanezumab) and mutation carriers in the pooled placebo group. 4) Rate of brain atrophy in treatment groups vs. pooled placebo group as measured by cortical thickness of regions of interest (volumetric MRI). 5) Change in FDG-PET metabolism in specific regions of interest in treated group as compared to pooled placebo group. 6) Exploratory cognitive and behavioral outcome measures 7) Exploratory imaging measures 8) Assess longitudinal change in biomarker and cognitive measures in individuals who do not have mutations causing dominantly inherited Alzheimer’s disease;Primary end point(s): The primary efficacy endpoint is specific for each drug based on mechanism of action. Each primary endpoint for	—

Measure

Time frame

Main Objective: 1. Assess safety and tolerability of gantenerumab and solanezumab in individuals who have mutations causing dominantly inherited Alzheimer’s disease. 2. Assess biological efficacy/target engagement of gantenerumab and solanezumab in individuals who have mutations causing dominantly inherited Alzheimer’s disease as measured by the primary biomarker measure for each drug. Primary endpoints are specified for each drug based on mechanism of action. Depending on proposed mechanism of action, the primary biomarker endpoint will be either 1) change in amyloid deposition as measured by [11C]PiB-PET composite standardized uptake value ratio (C-SUVR, average of precuneus, caudate, gyrus rectus, occipital cortex, parietal cortex, prefrontal cortex and temporal cortex) or, 2) changes in free and total amyloid beta (Aß) isoforms in CSF.;Secondary Objective: Secondary study endpoints will include: 1) Change in amyloid deposition as measured by [11C]PiB-PET C-SUVR (used as a secondary outcome measure when not the primary outcome measure). 2) Change in CSF amyloid-beta peptide concentrations (used as a secondary outcome measure when not the primary outcome measure). 3) Change of CSF biomarkers tau and ptau181 values compared between subjects on active drug (gantenerumab or solanezumab) and mutation carriers in the pooled placebo group. 4) Rate of brain atrophy in treatment groups vs. pooled placebo group as measured by cortical thickness of regions of interest (volumetric MRI). 5) Change in FDG-PET metabolism in specific regions of interest in treated group as compared to pooled placebo group. 6) Exploratory cognitive and behavioral outcome measures 7) Exploratory imaging measures 8) Assess longitudinal change in biomarker and cognitive measures in individuals who do not have mutations causing dominantly inherited Alzheimer’s disease;Primary end point(s): The primary efficacy endpoint is specific for each drug based on mechanism of action. Each primary endpoint for

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Secondary

Measure	Time frame
Secondary end point(s): Secondary study endpoints will include: 1) Change in amyloid deposition as measured by [11C]PiB-PET C-SUVR (used as a secondary outcome measure when not the primary outcome measure). 2) Change in CSF amyloid-beta peptide concentrations (used as a secondary outcome measure when not the primary outcome measure). 3) Change of CSF biomarkers tau and ptau181 values compared between subjects on active drug (gantenerumab or solanezumab) and mutation carriers in the pooled placebo group. 4) Rate of brain atrophy in treatment groups vs. pooled placebo group as measured by cortical thickness of regions of interest (volumetric MRI). 5) Change in FDG-PET metabolism in specific regions of interest (e.g., precuneus) in treated group as compared to pooled placebo group measured.;Timepoint(s) of evaluation of this end point: Same criteria as above for the primary endpoint.	—

Measure

Time frame

Secondary end point(s): Secondary study endpoints will include: 1) Change in amyloid deposition as measured by [11C]PiB-PET C-SUVR (used as a secondary outcome measure when not the primary outcome measure). 2) Change in CSF amyloid-beta peptide concentrations (used as a secondary outcome measure when not the primary outcome measure). 3) Change of CSF biomarkers tau and ptau181 values compared between subjects on active drug (gantenerumab or solanezumab) and mutation carriers in the pooled placebo group. 4) Rate of brain atrophy in treatment groups vs. pooled placebo group as measured by cortical thickness of regions of interest (volumetric MRI). 5) Change in FDG-PET metabolism in specific regions of interest (e.g., precuneus) in treated group as compared to pooled placebo group measured.;Timepoint(s) of evaluation of this end point: Same criteria as above for the primary endpoint.

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Countries

Australia, Canada, France, Germany, Italy, Spain, Sweden, United Kingdom, United States

Contacts

Public ContactSusan Mills, Sr. Project Manager

Washington University in St. Louis

millss@neuro.wustl.edu+1-949-293-5290

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026