The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD
Abstract INTRODUCTION In addition to the accumulation of amyloid plaques and neurofibrillary tangles, the presence of excess neural activity is a pathological hallmark of Alzheimer's disease (AD) and a prognostic indicator for progression of AD pathology and clinical/cognitive worsening in mild...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-01-01
|
| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/trc2.12446 |
| _version_ | 1797242810051592192 |
|---|---|
| author | Richard Mohs Arnold Bakker Sharon Rosenzweig‐Lipson Michael Rosenblum Russell L. Barton Marilyn S. Albert Sharon Cohen Scott Zeger Michela Gallagher |
| author_facet | Richard Mohs Arnold Bakker Sharon Rosenzweig‐Lipson Michael Rosenblum Russell L. Barton Marilyn S. Albert Sharon Cohen Scott Zeger Michela Gallagher |
| author_sort | Richard Mohs |
| collection | DOAJ |
| description | Abstract INTRODUCTION In addition to the accumulation of amyloid plaques and neurofibrillary tangles, the presence of excess neural activity is a pathological hallmark of Alzheimer's disease (AD) and a prognostic indicator for progression of AD pathology and clinical/cognitive worsening in mild cognitive impairment due to Alzheimer's disease (MCI due to AD). The HOPE4MCI clinical study tested the efficacy of a therapeutic with demonstrated ability to normalize heightened neural activity in the hippocampus in a randomized controlled trial of 78 weeks duration in patients with MCI due to AD. METHODS One hundred and sixty‐four participants were randomized to placebo (n = 83) or AGB101 (n = 81), an extended‐release formulation of low dose (220 mg) levetiracetam. The primary endpoint was the change in Clinical Dementia Rating Scale Sum of Boxes score (CDR‐SB) comparing follow up at 18 months to baseline. The goal of the primary efficacy analysis was to estimate the difference between the AGB101 and placebo arms in the mean change of the primary endpoint. RESULTS The mean change in CDR‐SB was estimated to be 1.12 (95% confidence interval [CI]: 0.66, 1.69) for the AGB101 arm and 1.22 (95% CI: 0.75, 1.78) for the placebo arm. The estimated difference between arms is ‐0.10 (95% CI: ‐0.85, 0.58), which was not statistically significant. In a prespecified analysis, the difference was ‐0.45 (95% CI: ‐1.43, 0.53) for ApoE‐4 noncarriers and ‐0.10 (95% CI: ‐0.92, 0.72) for apolipoprotein E (ApoE)‐4 carriers. DISCUSSION The possibility that ApoE‐4 carriers and noncarriers will respond differently to therapeutic intervention is consistent with recently reported findings from biologics and the present results show further testing of AGB101 in patients with MCI due to AD who are noncarriers of the ApoeE‐4 allele is warranted. Conclusions from the HOPE4MCI study are limited primarily due to the small sample size and results can only be regarded as a guide to future research. |
| first_indexed | 2024-04-24T18:45:08Z |
| format | Article |
| id | doaj.art-42aaa9d7842c4b72aeecc5f9cb9624d9 |
| institution | Directory Open Access Journal |
| issn | 2352-8737 |
| language | English |
| last_indexed | 2024-04-24T18:45:08Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj.art-42aaa9d7842c4b72aeecc5f9cb9624d92024-03-27T07:00:57ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372024-01-01101n/an/a10.1002/trc2.12446The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to ADRichard Mohs0Arnold Bakker1Sharon Rosenzweig‐Lipson2Michael Rosenblum3Russell L. Barton4Marilyn S. Albert5Sharon Cohen6Scott Zeger7Michela Gallagher8AgeneBio, Inc. Baltimore Maryland USADepartment of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland USAAgeneBio, Inc. Baltimore Maryland USADepartment of Biostatistics Johns Hopkins University Bloomberg School of Public Health Baltimore Maryland USAAgeneBio, Inc. Baltimore Maryland USADepartment of Neurology Johns Hopkins University School of Medicine Baltimore Maryland USAToronto Memory Program Toronto Ontario CanandaDepartment of Biostatistics Johns Hopkins University Bloomberg School of Public Health Baltimore Maryland USAAgeneBio, Inc. Baltimore Maryland USAAbstract INTRODUCTION In addition to the accumulation of amyloid plaques and neurofibrillary tangles, the presence of excess neural activity is a pathological hallmark of Alzheimer's disease (AD) and a prognostic indicator for progression of AD pathology and clinical/cognitive worsening in mild cognitive impairment due to Alzheimer's disease (MCI due to AD). The HOPE4MCI clinical study tested the efficacy of a therapeutic with demonstrated ability to normalize heightened neural activity in the hippocampus in a randomized controlled trial of 78 weeks duration in patients with MCI due to AD. METHODS One hundred and sixty‐four participants were randomized to placebo (n = 83) or AGB101 (n = 81), an extended‐release formulation of low dose (220 mg) levetiracetam. The primary endpoint was the change in Clinical Dementia Rating Scale Sum of Boxes score (CDR‐SB) comparing follow up at 18 months to baseline. The goal of the primary efficacy analysis was to estimate the difference between the AGB101 and placebo arms in the mean change of the primary endpoint. RESULTS The mean change in CDR‐SB was estimated to be 1.12 (95% confidence interval [CI]: 0.66, 1.69) for the AGB101 arm and 1.22 (95% CI: 0.75, 1.78) for the placebo arm. The estimated difference between arms is ‐0.10 (95% CI: ‐0.85, 0.58), which was not statistically significant. In a prespecified analysis, the difference was ‐0.45 (95% CI: ‐1.43, 0.53) for ApoE‐4 noncarriers and ‐0.10 (95% CI: ‐0.92, 0.72) for apolipoprotein E (ApoE)‐4 carriers. DISCUSSION The possibility that ApoE‐4 carriers and noncarriers will respond differently to therapeutic intervention is consistent with recently reported findings from biologics and the present results show further testing of AGB101 in patients with MCI due to AD who are noncarriers of the ApoeE‐4 allele is warranted. Conclusions from the HOPE4MCI study are limited primarily due to the small sample size and results can only be regarded as a guide to future research.https://doi.org/10.1002/trc2.12446AGB101Alzheimer's diseaseclinical trialhippocampuslevetiracetammild cognitive impairment |
| spellingShingle | Richard Mohs Arnold Bakker Sharon Rosenzweig‐Lipson Michael Rosenblum Russell L. Barton Marilyn S. Albert Sharon Cohen Scott Zeger Michela Gallagher The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD Alzheimer’s & Dementia: Translational Research & Clinical Interventions AGB101 Alzheimer's disease clinical trial hippocampus levetiracetam mild cognitive impairment |
| title | The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD |
| title_full | The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD |
| title_fullStr | The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD |
| title_full_unstemmed | The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD |
| title_short | The HOPE4MCI study: A randomized double‐blind assessment of AGB101 for the treatment of MCI due to AD |
| title_sort | hope4mci study a randomized double blind assessment of agb101 for the treatment of mci due to ad |
| topic | AGB101 Alzheimer's disease clinical trial hippocampus levetiracetam mild cognitive impairment |
| url | https://doi.org/10.1002/trc2.12446 |
| work_keys_str_mv | AT richardmohs thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT arnoldbakker thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT sharonrosenzweiglipson thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT michaelrosenblum thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT russelllbarton thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT marilynsalbert thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT sharoncohen thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT scottzeger thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT michelagallagher thehope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT richardmohs hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT arnoldbakker hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT sharonrosenzweiglipson hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT michaelrosenblum hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT russelllbarton hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT marilynsalbert hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT sharoncohen hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT scottzeger hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad AT michelagallagher hope4mcistudyarandomizeddoubleblindassessmentofagb101forthetreatmentofmciduetoad |