A Study to Evaluate the Pharmacodynamic (PD) Effects of Once Weekly Administration of Gantenerumab in Participants With Early Alzheimer's Disease (AD)

March 1, 2024 updated by: Hoffmann-La Roche

A Phase II, Multicenter, Open-Label, Single Arm Study to Evaluate the Pharmacodynamic Effects of Once Weekly Administration of Gantenerumab in Participants With Early (Prodromal to Mild) Alzheimer's Disease

This is a Phase II, multicenter, open-label, single arm, PD study in participants with early (prodromal to mild) AD to evaluate the effect of a once weekly (Q1W) dosing regimen of gantenerumab on deposited amyloid as measured by change from baseline to Week 104 (primary) and Week 208 in brain amyloid positron emission tomography (PET). The administration of gantenerumab as a single injection of Q1W will be investigated in this study, to simplify the dosing regimen for participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
192

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

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

  • Belgium
      • Hasselt, Belgium, 3500
        • Jessa Zkh (Campus Virga Jesse)
      • Kortrijk, Belgium, 8500
        • AZ Groeninge
      • Leuven, Belgium, 3000
        • UZ Leuven Gasthuisberg
  • France
      • Bron cedex, France, 69677
        • Groupement Hospitalier Est - Hôpital Neurologique; Neurologie A (U502)
      • Paris, France, 75651
        • CH Pitie Salpetriere; IM2A
      • Toulouse, France, 31059
        • Gerontopole; Centre de Recherche clinique
  • Germany
      • Berlin, Germany, 13125
        • ECRC Experimental and Clinical Research Center, Charité Campus Berlin Buch, Memory Clinic
      • Berlin, Germany, 12200
        • Ambulates Gesundheitszentrum der Charité GmbH; MVZ Neurologie Campus Benjamin Franklin
      • München, Germany, 81675
        • Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
  • Italy
    • Lazio
      • Roma, Lazio, Italy, 00186
        • Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
    • Lombardia
      • Milano, Lombardia, Italy, 20132
        • Fondazione San Raffaele Del Monte Tabor; Dipartimento Di Neurologia
    • Puglia
      • Tricase (LE), Puglia, Italy, 73039
        • Ospedale Cardinale Panico; Dip.Ricerca Clinica in Neurologia ? UO Malattie Neurodegenerative
  • Poland
      • Bydgoszcz, Poland, 85-079
        • NZOZ Vitamed
      • Lublin, Poland, 20-410
        • Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
      • Sopot, Poland, 81-855
        • Senior Sp. Z O.O. Poradnia Psychogeriatryczna
      • Szczecin, Poland, 70-111
        • Centrum Medyczne Euromedis Sp. z o.o.
      • Warszawa, Poland, 01-684
        • Centrum Medyczne NeuroProtect
      • Wroc?aw, Poland, 53-659
        • NZOZ WCA
  • Spain
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre; Servicio de Neurologia
      • Madrid, Spain, 28006
        • Hospital Universitario de la Princesa; Servicio de Neurologia
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe; Servicio de Neurología
    • Guipuzcoa
      • Donostia-san Sebastian, Guipuzcoa, Spain, 20014
        • Policlínica Guipuzcoa; Servicio de Neurología
    • Madrid
      • Pozuelo de Alarcon, Madrid, Spain, 28223
        • Hospital Quiron de Madrid; Servicio de Neurologia
  • United Kingdom
      • Birmingham, United Kingdom, B16 8QQ
        • Re-Cognition
      • Cheltenham, United Kingdom, GL53 9DZ
        • Fritchie Centre
      • Dundee, United Kingdom, DD12 9SY
        • Ninewells Hospital
      • London, United Kingdom, W6 8RF
        • Charing Cross Hospital; Imperial Memory Unit, Level 10 West
  • United States
    • Florida
      • Atlantis, Florida, United States, 33462
        • JEM Research LLC
      • Maitland, Florida, United States, 32751
        • ClinCloud, LLC
      • Ocala, Florida, United States, 34470
        • Renstar Medical Research
      • Wellington, Florida, United States, 33414
        • Alzheimer?s Research and Treatment Center
    • Georgia
      • Gainesville, Georgia, United States, 30501
        • Center for Advanced Research & Education
    • Oregon
      • Portland, Oregon, United States, 97210
        • Summit Research Network Inc.
    • Pennsylvania
      • Willow Grove, Pennsylvania, United States, 19090
        • Abington Neurological Associates Willow Grove

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Probable Alzheimer's Disease (AD) dementia or prodromal AD.
  • Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
  • The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
  • Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
  • Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
  • Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score >/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score >/=0.5.
  • If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
  • Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug.
  • Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.

Exclusion Criteria:

  • Any evidence of a condition other than AD that may affect cognition.
  • History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
  • History or presence of clinically evident cerebrovascular disease.
  • History or presence of posterior reversible encephalopathy syndrome.
  • History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
  • History of severe, clinically significant CNS trauma.
  • History or presence of intracranial mass that could potentially impair cognition.
  • Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
  • History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
  • History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
  • At risk for suicide in the opinion of the investigator.
  • Alcohol and/or substance abuse or dependants in past 2 years.

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: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Gantenerumab
Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.
Drug: Gantenerumab
Gantenerumab will be administered by SC injection at a dose of 120 mg Q4W for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg Q2W for another 12 weeks, followed by the target dose 255 mg Q1W for up to Week 103 and an optional dose of 255 mg Q1W for up to Week 207.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan
Time Frame: Baseline, Week 104
Screening amyloid PET scan was considered baseline evaluation.Brain amyloid load was quantified in terms of Standardized Uptake Value Ratio (SUVR),defined as ratio of tracer uptake in cortical composite target region of interest(ROI)to tracer uptake in reference ROI.Composite region: frontal,parietal,temporal,posterior cingulate cortex,anterior cingulate cortex. Reference ROI (whole cerebellum) was represented by weighted average of Cerebellum Ventral,Cerebellum Dorsal (left/right), Cerebellar White Matter.SUVR linearly transformed to standardized Centiloid Scale (CL) using formula CL=175.6xSUVR-174.2.CL ranges from <0 to >100, anchor points are 0=high-certainty amyloid negative scan and 100=amount of global amyloid deposition found in typical AD scan.
Baseline, Week 104

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Caregiver or Study Partner With Responses to Home Administration Questionnaire (HAQ)
Time Frame: Weeks 36, 52, 76, 104
HAQ comprised 4 items completed by study partner capturing confidence (Q1), convenience (Q2), ease of use (Q3), and overall satisfaction (Q4) with administering medication. Response options Q1: Not at all confident, somewhat confident, confident, very confident; Q2: Not at all convenient, somewhat convenient, convenient, very convenient; Q3: Not at all easy, somewhat easy, easy, very easy; Q4:Not at all satisfied, somewhat satisfied, satisfied, very satisfied.
Weeks 36, 52, 76, 104
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
AE: any untoward medical occurrence in participant administered pharmaceutical product, which does not necessarily have a causal relationship with treatment. Also, any unfavorable, unintended sign, symptom, or disease temporally associated with use of medicinal product, whether or not considered related to it. SAE: any AE that was fatal, life threatening, required prolonged inpatient hospitalization, resulted in significant disability or resulted in a congenital anomaly to mother exposed to study treatment. This was a single-arm study and all participants received gantenerumab according to predefined universal up-titration scheme as follows: 120 mg Q4W (Day 1, Week (W) 4, and W8), then 255 mg Q4W (W 12, 16, and 20), then 255 mg Q2W for 12 weeks (W 24, 26, 28, 30, 32, and 34), followed by target dose of 255 mg Q1W (W 36 to 104). Data was collected and reported in single arm for each participant who started treatment as specified and either completed or discontinued study.
From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods(Not Plan)without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal);Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior. Categories with non-zero values are only reported here.
From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)
Time Frame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. The occurrences of imaging abnormalities in vasogenic edema and sulcal effusions (ARIA-E) were evaluated.
From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)
Time Frame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
ARIA are an identified risk with anti-amyloid antibodies, including gantenerumab. These changes can be identified on brain MRI. ARIA-H (H for hemosiderosis) are small foci of signal loss observed on MRI sequences sensitive for paramagnetic tissue properties and comprise cerebral microbleeds (small foci of bleeding in the brain parenchyma) and leptomeningeal hemosiderosis (small foci of bleeding on the surface of the brain). These changes also occur sporadically in AD.
From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
Number of Participants With Injection-Site Reactions (ISR)
Time Frame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational product or other protocol-imposed intervention, regardless of attribution. Injection reactions (local and systemic) were defined as AEs that occured during or within 24 hours after study drug administration that were judged to be related to the study drug injection.
From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
Number of Participants With Treatment-emergent Anti-Drug Antibodies to Gantenerumab
Time Frame: From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
A participant with an ADA assay result from at least one post-baseline sample was defined as a post-baseline evaluable participant. Treatment Emergent ADA was defined as a participant with a negative or missing baseline ADA result(s) and at least one positive post-baseline ADA result, or a participant with a positive ADA result at baseline who has at least one post-baseline titer results with at least a >2.5-fold increase in titer compared to baseline greater than the baseline titer result.
From day of first dose up to 16 weeks after the last dose (up to 120 weeks)
Plasma Concentration of Subcutaneous (SC) Gantenerumab at Specified Timepoints
Time Frame: Day 4 of Week 1, Week 24, 36, 52, and 76
Day 4 of Week 1, Week 24, 36, 52, and 76
Change in Brain Amyloid Based on Different Dosing Frequency
Time Frame: Baseline up to Week 52
The change from baseline at Week 52 using the once-weekly dosing frequency was analysed using the centiloid scale. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scan. The range of centiloid values can be below 0 (negative) and greater than 100.
Baseline up to Week 52

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 18, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 11, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 15, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 2, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 19, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WN29722
  • 2020-001384-87 (Registry Identifier: EudraCT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

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.

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