Amyloid-β11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials
| Autor: | Liu, Enchi, Schmidt, Mark E, Margolin, Richard, Sperling, Reisa, Koeppe, Robert, Mason, Neale S, Klunk, William E, Mathis, Chester A, Salloway, Stephen, Fox, Nick C, Hill, Derek L, Les, Andrea S, Collins, Peter, Gregg, Keith M, Di, Jianing, Lu, Yuan, Tudor, I Cristina, Wyman, Bradley T, Booth, Kevin, Broome, Stephanie, Yuen, Eric, Grundman, Michael, Brashear, H Robert, Bapineuzumab 301 and 302 Clinical Trial Investigators |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Aging Pathology Bapineuzumab 301 and 302 Clinical Trial Investigators Apolipoprotein B Apolipoprotein E4 Neurodegenerative Alzheimer's Disease Gastroenterology law.invention Randomized controlled trial law Monoclonal 80 and over Humanized Aged 80 and over Cerebral Cortex Aniline Compounds biology Middle Aged Treatment Outcome 6.1 Pharmaceuticals Neurological Biomedical Imaging Female Cognitive Sciences Alzheimer's disease medicine.drug Heterozygote medicine.medical_specialty Clinical Trials and Supportive Activities Clinical Sciences Standardized uptake value Antibodies Monoclonal Humanized Placebo Antibodies Alzheimer Disease Clinical Research Internal medicine Acquired Cognitive Impairment medicine Humans Dementia Bapineuzumab Benzothiazoles Aged Amyloid beta-Peptides Neurology & Neurosurgery business.industry Neurosciences Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) Evaluation of treatments and therapeutic interventions medicine.disease Brain Disorders Clinical trial Thiazoles Positron-Emission Tomography biology.protein Neurology (clinical) business |
| Zdroj: | Neurology, vol 85, iss 8 |
| ISSN: | 1526-632X 0028-3878 |
| Popis: | Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using 11 C-Pittsburgh compound B ( 11 C-PiB)-PET. Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE e4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an 11 C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region. Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in 11 C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = −0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = −0.068; p = 0.027; 1.0 mg/kg vs placebo δ = −0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results. Conclusions: The 11 C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted. |
| Databáze: | OpenAIRE |
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