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 (DIAN-TU)

January 9, 2025 updated by: Washington University School of Medicine

A Phase II/III Multicenter Randomized, Double-Blind, Placebo-Controlled Platform Trial of Potential Disease Modifying Therapies Utilizing Biomarker, Cognitive, and Clinical Endpoints in Dominantly Inherited Alzheimer's Disease

The purpose of this study is to assess the safety, tolerability, biomarker, cognitive and clinical efficacy of investigational products in participants with an Alzheimer's disease-causing mutation by determining if treatment with the study drug slows the rate of progression of cognitive/clinical impairment or improves disease-related biomarkers.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Alzheimer's disease (AD) is defined by the presence of abnormal accumulations of amyloid protein (plaques) and tau protein (tangles) in the brain. The double-blind arm of DIAN-TU-001 Master protocol (NCT01760005) tested whether gantenerumab provided a clinical benefit by slowing the onset or the worsening of the disease. A clinical benefit was not observed in the double-blind part of the DIAN-TU-001 study. However, gantenerumab was associated with improvements in measures of amyloid and tau and an improvement in an overall measure of neurodegeneration (when nerve cells in the brain lose function over time). It is not known whether these changes may provide future clinical benefits. Based on this information, an exploratory Open Label Extension (OLE) will further study the effect of gantenerumab on these Alzheimer-related proteins and their relationship to disease progression.

After this final evaluation of study treatment with gantenerumab used in the gantenerumab / solanezumab double-blind arm of the Master protocol (NCT01760005), eligible participants from the placebo, solanezumab, and gantenerumab treatment groups in double-blind period were invited to participate in an OLE period to receive active gantenerumab study treatment as part of the DIAN-TU-001 Master protocol. The OLE period of the study planned to provide study treatment with gantenerumab for up to 3 years (36 months).

This study collected brain scans, blood, and spinal fluid tests (also called biomarkers), as well as safety, clinical and cognitive testing. The goal is to determine if gantenerumab has favorable effects on these tests to determine if and how much treatment may prevent or delay the symptoms of AD.

Update:

Based on the results of the completed studies of gantenerumab in sporadic AD in late 2022, it was decided to determine if dominantly inherited Alzheimer's disease (DIAD) participants in the DIAN-TU-001 OLE study were substantially clinically benefiting from gantenerumab high-dose treatment before the trial reached completion as the Gant program was being stopped.

An interim efficacy analysis of the DIAN-TU-001 OLE was performed to:

  1. determine if gantenerumab OLE treatment and/or long-term treatment results in clinical benefit and determine the extent of amyloid removal compared to the double-blind period.
  2. determine the potential effects of gantenerumab on clinical and cognitive measures to support decision-making regarding next steps for the DIAN-TU-001 OLE.

Study Type

Interventional

Enrollment (Actual)

73

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Neuroscience Research Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3010
        • Mental Health Research Institute
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • The McCuster Foundation of Alzheimer's Disease Research
  • France
    • Haute Garonne
      • Toulouse, Haute Garonne, France, 31059
        • CHU de Toulouse - Hôpital Purpan
    • Paris
      • Paris cedex 13, Paris, France, 69677
        • Groupe Hospitalier Pitie-Salpetriere
    • Seine Maritime
      • Rouen, Seine Maritime, France, 76031
        • CHU de Rouen - Hôpital Charles Nicolle
  • Puerto Rico
      • San Juan, Puerto Rico, 00936
        • University of Puerto Rico, School of Medicine
  • Spain
      • Barcelona, Spain, 8036
        • Hospital Clínic i Provincial de Barcelona
  • United Kingdom
    • Greater London
      • London, Greater London, United Kingdom, WC1B 3BG
        • The National Hospital for Neurology and Neurosurgery
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama in Birmingham
    • California
      • La Jolla, California, United States, 92037
        • University of California San Diego Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30329
        • Emory University
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University in St. Louis
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02096
        • Butler Hospital
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Between 18-80 years of age
  • Individuals who know they have an Alzheimer's disease-causing mutation
  • Individuals who have participated in the double-blind period
  • In the opinion of the investigator and sponsor, treatment is not contraindicated for safety
  • Capable of receiving drug and appropriate clinical safety assessment
  • Able to undergo Magnetic Resonance Imaging (MRI), Lumbar Puncture (LP), Positron Emission Tomography (PET), and complete all study related testing and evaluations.
  • For women of childbearing potential, if partner is not sterilized, subject must agree to use effective contraceptive measures (hormonal contraception, intra-uterine device, sexual abstinence, barrier method with spermicide).
  • Adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments.
  • Has a Study Partner who in the investigator's judgment is able to provide accurate information as to the subject's cognitive and functional abilities, who agrees to provide information at the study visits which require informant input for scale completion.

Exclusion Criteria:

  • History or presence of brain MRI scans indicative of any other significant abnormality
  • Alcohol or drug dependence currently or within the past 1 year
  • Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin or body which would preclude MRI scan.
  • History or presence of clinically significant cardiovascular disease, hepatic/renal disorders, infectious disease or immune disorder, or metabolic/endocrine disorders
  • Anticoagulants except low dose (≤ 325 mg) aspirin.
  • Have been exposed to a monoclonal antibody targeting beta amyloid peptide within the past six months.
  • History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years.
  • Positive urine or serum pregnancy test or plans or desires to become pregnant during the course of the trial.
  • Subjects unable to complete all study related testing, including implanted metal that cannot be removed for MRI scanning, required anticoagulation and pregnancy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Gantenerumab Open Label Extension
Gantenerumab: Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks
Drug: Gantenerumab
Open-label administered Subcutaneously every 4 weeks, at escalating doses; at target, dosing was every 2 weeks
Other Names:
  • RO4909832

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Composite [11C] Pittsburgh Compound B (PiB)-Positron Emission Tomography (PET) Composite Standardized Uptake Value Ratio (C-SUVR) at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The composite PiB partial volume corrected C-SUVR was used as the biomarker endpoint for amyloid deposition using PET. The C-SUVR of precuneus, caudate, gyrus rectus, occipital cortex, parietal cortex, prefrontal cortex, and temporal cortex of brain regions was analyzed. Higher ratio indicate worse disease stage. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Clinical Dementia Rating (CDR) - Sum of Boxes Score at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CDR - sum of boxes. The CDR-SB score is considered a more detailed quantitative general index of cognition and function than the global CDR score. The CDR - sum of boxes is the sum score of 6 domains of cognitive function (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care), with the score of each domain ranging from 0 (no impairment) to 3 (severe impairment). The total score ranges from 0 (no impairment) to 18 (severe impairment). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Clinical Dementia Rating - Global Score at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CDR - global score. The score ranges from 0 (minimum) to 3 (maximum). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Functional Assessment Scale (FAS) at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by FAS. This scale measured instrumental activities of daily living such as preparing balanced meals and managing personal finances. The intent of the FAS was to assess change in an individual's functional activities, relative to previously attained abilities, that were caused by cognitive dysfunction. The score ranges from 0 (minimum) to 30 (maximum). Higher score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Mini-Mental State Examination (MMSE) at Weeks 24, 52, 76, 104, 128 and 156
Time Frame: Baseline (Day 1) and Weeks 24, 52, 76, 104, 128 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by MMSE. The MMSE is a brief, quantitative measure of cognitive status in adults used to screen for cognitive impairment. The score ranges from 0 (minimum) to 30 (maximum). Lower score indicates worse performance. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 24, 52, 76, 104, 128 and 156
Change From Baseline in Tau Positron Emission Tomography Binding Partial Volume Corrected Standardized Uptake Value Ratio (Tau PET SUVR) at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by Tau PET SUVR. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Phosphorylated Tau (pTau)-181 in Cerebrospinal Fluid (CSF) at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CSF pTau-181. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Neurofilament Light Chain (NfL) in Cerebrospinal Fluid at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CSF NfL. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in Amyloid Beta1-42/40 Ratio in Cerebrospinal Fluid at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156
The efficacy of gantenerumab in reducing disease progression was assessed by CSF Amyloid Beta1-42/40. Baseline was defined as the last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156
Change From Baseline in DIAN-TU Open Label Extension Cognitive Composite Score at Weeks 52, 104 and 156
Time Frame: Baseline (Day 1) and Weeks 52, 104 and 156

The efficacy of gantenerumab in reducing disease progression was assessed by DIAN-TU OLE Cognitive Composite. The cognitive composite was calculated based on the below 4 components,

  1. The wechsler adult intelligence scale-revised digit span (backward recall). Score ranges from 0 (minimum) to 7 (maximum).
  2. The category fluency (animals) value. Score ranges from 0 to unlimited.
  3. The wechsler adult intelligence scale digit symbol substitution test. Score ranges from 0 (minimum) to 93 (maximum).
  4. The MMSE. Score ranges from 0 (minimum) to 30 (maximum).

Lower scores of each component indicate worse performance. The cognitive composite is a normalized z score and has score range - 4.11 to unlimited as one of the components has score range 0 to unlimited. Lower score indicates worse performance. Baseline was defined as last non-missing measurement prior to OLE study drug administration.
Baseline (Day 1) and Weeks 52, 104 and 156

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Washington University School of Medicine

Collaborators

Hoffmann-La Roche
National Institute on Aging (NIA)
Alzheimer's Association

Investigators

  • Study Director: Randall J Bateman, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 3, 2020

Primary Completion (Actual)

October 6, 2023

Study Completion (Actual)

November 13, 2023

Study Registration Dates

First Submitted

April 16, 2024

First Submitted That Met QC Criteria

May 15, 2024

First Posted (Actual)

May 22, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 9, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DIAN-TU-001 (Gant OLE)
  • The Alzheimer's Association (Other Grant/Funding Number: DIAN-TU-OLE-21-725093)
  • U01AG042791 (U.S. NIH Grant/Contract)
  • 2013-000307-17 (EudraCT Number)
  • R01AG046179 (U.S. NIH Grant/Contract)
  • REec-2014-0817 (Registry Identifier: Spanish Clinical Studies Registry)
  • GHR Foundation (Other Grant/Funding Number: File 4401)
  • Alzheimer's Association (Other Identifier: HDE 18S84914)
  • R56AG053267 (U.S. NIH Grant/Contract)
  • U01AG059798 (U.S. NIH Grant/Contract)
  • R01AG053267 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Access to DIAN-TU trial data will follow the DIAN-TU data access policy, which complies with the guidelines established by the Collaboration for Alzheimer's Prevention [CAP REF].

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Dementia

Clinical Trials on Gantenerumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe