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| Name | Class |
|---|---|
| Banner Alzheimer's Institute | OTHER |
| National Institute on Aging (NIA) | NIH |
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This substudy will evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352). Participants will receive up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of [18^F]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| [^18F]GTP1 in Mutation Carriers: Crenezumab | Experimental | Mutation-carrying participants receiving crenezumab in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1. |
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| [^18F]GTP1 in Mutation Carriers: Placebo | Placebo Comparator | Mutation-carrying participants receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1. |
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| [^18F]GTP1 in Non-carriers of Mutation: Placebo | Placebo Comparator | Non-carriers of the mutation receiving placebo in the main study NCT01998841 (GN28352) will receive up to three IV injections of [^18F]GTP1 and will undergo a tau PET scan after each IV injection of [^18F]GTP1. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Crenezumab | Drug | Crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Annualized Rate of Change in Tau Burden | Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using [18F]GTP1 Tau PET. The annualized rate of change in tau burden from the first [18F]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement. | Baseline up to Week 149 |
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Inclusion Criteria:
- Enrolled in main Study NCT01998841 (GN28352).
Exclusion Criteria:
- Contraindication to PET scan procedures, possibly including, but not limited to current, past, or planned participation in studies involving radioactive agents, including the main Study NCT01998841 (GN28352) and this Tau PET substudy, such that the total research-related radiation dose to the participant in any given year would exceed the limits set forth in the U.S. Code of Federal Regulations (CFR) Title 21 Section 361.
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Grupo Neurociencias de Antioquia | Medellín | Colombia |
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/members/ourmembers/). 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).
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114 participants enrolled in this sub-study.
This sub-study enrolled participants from the main study: NCT01998841, who consented to participate in it. Participants took part in this sub-study from 10 Jun 2019 to 19 Apr 2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Crenezumab - Mutation Carriers | Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 milligrams (mg), subcutaneously (SC), every two weeks (Q2W), or 60 milligrams per kilograms (mg/kg), intravenously (IV), every four weeks (Q4W) in the main study (NCT01998841) received up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and underwent a tau positron emission tomography (PET) scan after each IV injection of [^18F]GTP1. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 11, 2020 |
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| Placebo | Drug | Placebo matched to crenezumab will be administered subcutaneously (every 2 weeks) or IV (every 4 weeks) for at least 260 weeks. |
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| [^18F]GTP1 | Other | IV [^18F]GTP1 will be administered up to three times. The first primary [^18F]GTP1 tau PET scan will occur during any visit in the main protocol NCT01998841 (GN28352) from Week 130 to Week 224 and the second [^18F]GTP1 tau PET scan from Week 248 to Week 260. The third and optional [^18F]GTP1 tau PET scan will supplement the two primary scans. |
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| FG001 | Placebo - Mutation Carriers | Participants who were PSEN1 E280A mutation carriers and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. |
| FG002 | Placebo - Non-Carriers of Mutation | Participants who were non-carriers of PSEN1 E280A mutation and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. |
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| NOT COMPLETED |
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Intent-to-Treat population (ITT) population included all randomized participants who received the assigned study treatment
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| ID | Title | Description |
|---|---|---|
| BG000 | Crenezumab - Mutation Carriers | Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. |
| BG001 | Placebo - Mutation Carriers | Participants who were PSEN1 E280A mutation carriers and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. |
| BG002 | Placebo - Non-Carriers of Mutation | Participants who were non-carriers of PSEN1 E280A mutation and were administered crenezumab matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Annualized Rate of Change in Tau Burden | Tau is a protein that accumulates in Alzheimer's disease and damages brain cells including those essential for learning and memory. The effect of crenezumab on tau burden was assessed using [18F]GTP1 Tau PET. The annualized rate of change in tau burden from the first [18F]GTP1 scan of the standardized uptake ratio (SUVR) in the entorhinal cortex (Braak Stage 1) with an inferior cerebellum reference region was analyzed using a random coefficient regression model (RCRM). Braak staging classifies the degree of pathology in Alzheimer's disease. Braak stages 1 and 2 are used when neurofibrillary tangle involvement is confined mainly to the transentorhinal region of the brain, stages 3 and 4 when there is also involvement of limbic regions such as the hippocampus, and 5 and 6 when there is extensive neocortical involvement. | Modified Intent-to-Treat (mITT) population included all mutation carrier participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug. | Posted | Mean | Standard Error | SUVR per year | Baseline up to Week 149 |
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Up to Week 149
Safety population included all participants randomized in Study GN28352 (NCT01998841) and consented to the tau PET substudy who had received at least 1 dose of study drug; participants were grouped according to the actual treatment received and the mutation status. Pooled data has been reported for the SAEs and non-serious AEs in order to maintain blinding of the participant's mutation status and treatment group.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Crenezumab - Mutation Carriers | Participants who were PSEN1 E280A mutation carriers and were administered crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F] GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. | 0 | 44 | 4 | 44 | 43 | 44 |
| EG001 | Pooled Placebo | Carriers and non-carriers of PSEN1 E280A mutation who received matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841), received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. | 0 | 70 | 5 | 70 | 67 | 70 |
| EG002 | Combined Blinded | All participants who were carriers and non-carriers of PSEN1 E280A mutation and who received either crenezumab, 720 mg, SC, Q2W, or 60 mg/kg, IV, Q4W or matching placebo SC, Q2W or IV, Q4W in the main study (NCT01998841) received up to three IV injections of [^18F]GTP1 and underwent a tau PET scan after each IV injection of [^18F]GTP1. | 0 | 114 | 9 | 114 | 110 | 114 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA version: 25.0 | Systematic Assessment |
| |
| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA version: 25.0 | Systematic Assessment |
| |
| General disorders and administration site conditions | General disorders | MedDRA version: 25.0 | Systematic Assessment |
| |
| Infections and infestations | Infections and infestations | MedDRA version: 25.0 | Systematic Assessment |
| |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version: 25.0 | Systematic Assessment |
| |
| Pregnancy, puerperium and perinatal conditions | Pregnancy, puerperium and perinatal conditions | MedDRA version: 25.0 | Systematic Assessment |
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| Psychiatric disorders | Psychiatric disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Renal and urinary disorders | Renal and urinary disorders | MedDRA version: 25.0 | Systematic Assessment |
| |
| Reproductive system and breast disorders | Reproductive system and breast disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infections and infestations | Infections and infestations | MedDRA version: 25.0 | Systematic Assessment |
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| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA version: 25.0 | Systematic Assessment |
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| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Nervous system disorders | Nervous system disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Psychiatric disorders | Psychiatric disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA version: 25.0 | Systematic Assessment |
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| General disorders and administration site conditions | General disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Reproductive system and breast disorders | Reproductive system and breast disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Metabolism and nutrition disorders | Metabolism and nutrition disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Renal and urinary disorders | Renal and urinary disorders | MedDRA version: 25.0 | Systematic Assessment |
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| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | MedDRA version: 25.0 | Systematic Assessment |
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The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| BN40199 | Hoffmann-La Roche | 888-662-6728 (U.S. Only) | global-roche-genentech-trials@gene.com |
| Jan 25, 2024 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C573372 | crenezumab |
| C000710691 | (18F)GTP1 |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Black or African American |
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| Native Hawaiian or Other Pacific Islander |
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| White |
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| Multiple |
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| Other |
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| Unknown |
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