 |
8 Diseases |  |
0 Trials |
|
0 Trials |  |
104 News |  |
| 12» |
- | atabecestat (JNJ-54861911) / J&J
Journal: Molecular docking analysis of marine phytochemicals with BACE-1. (Pubmed Central) - Mar 18, 2024
2583 compounds, retrieved from Comprehensive Marine Natural Product Database (CMNPD), were primarily screened for drug-likeliness and blood-brain barrier permeability using admetSAR 2.0 and in-house BBBper tool and resulted in a total of 635 phytochemicals, selected for further docking studies using BACE-1 as target receptor and Atabecestat as standard BACE-1 inhibitor...These compounds are worth investigating further to assess their neuroprotective efficacy and pharmacokinetic properties. The study also provides a rational framework to uncover novel pharmacophores from marine sources for AD therapy acting through BACE-1 inhibition.
- | atabecestat (JNJ-54861911) / J&J
Journal: Genome-wide association study of abnormal elevation of ALT in patients exposed to atabecestat. (Pubmed Central) - Sep 7, 2023
The study also provides a rational framework to uncover novel pharmacophores from marine sources for AD therapy acting through BACE-1 inhibition. The suggestive GWAS signals in the case-control GWAS analysis suggest the potential role of inflammation in atabecestat-induced liver enzyme elevation.
- atabecestat (JNJ-54861911) / J&J, verubecestat (MK-8931) / Merck (MSD), umibecestat (CNP520) / Novartis, Amgen, Banner Alzheimer's Institute
Human CSF pharmacoproteomics establishes in vivo-relevant BACE1 substrates as pharmacodynamic biomarkers for chronic BACE inhibition in clinical trials (Elicium 2 (RAI Amsterdam Convention Centre)) - Jul 6, 2023 - Abstract #AAIC2023AAIC_9013;
A reduction of the inhibitor dose to less than 50% BACE1 inhibition may be an appropriate strategy to avoid side effects in future clinical trials with BACE inhibitors. Our analysis also demonstrates that proteomics enables pharmacodynamic studies of multiple CSF proteins in single measurements, which are suitable for precision medicine approaches in future clinical trials with BACE inhibitors.
- atabecestat (JNJ-54861911) / J&J
ASSESSING CLINICALLY MEANINGFUL FUNCT IONAL OUTCOMES IN PRECLINICAL ALZHEIMER’S DISEASE. () - Dec 9, 2022 - Abstract #CTAD2022CTAD_435;
While CFI and CFIa were well-correlated, the level of correlation did not indicate a redundancy between measures indicating these tools may measure different aspects of function. Results of this analysis provide important information All abstracts are embargoed until the day and time of presentation at the CTAD Conference S187 on the sensitivity of these functional assessments to amyloid pathology and to neurocognitive assessment.
- | Journal: BACE1: a key regulator in Alzheimer's disease progression and current development of its inhibitors. (Pubmed Central) - May 29, 2022
BACE1 is involved in the progression of AD. The current ongoing or failed clinical trials may help understand the role of BACE1 inhibition in regulating the Aβ load and cognitive status of AD patients.
- ||| atabecestat (JNJ-54861911) / J&J
Clinical, P2/3 data, P2b data, Preclinical, Journal: Sensitivity of the Preclinical Alzheimer's Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer's Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial. (Pubmed Central) - May 18, 2022
The Aβ+/- group effect was statistically larger for PACC and marginally larger for PACC5 versus RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.
- ||| atabecestat (JNJ-54861911) / J&J
Clinical, P2/3 data, P2b data, Preclinical, Journal: Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease: A Truncated Randomized Phase 2b/3 Clinical Trial. (Pubmed Central) - Jan 12, 2022
P2b
Atabecestat treatment was associated with dose-related cognitive worsening as early as 3 months and presence of neuropsychiatric treatment-emergent AEs, with evidence of reversibility after 6 months off treatment. ClinicalTrials.gov Identifier: NCT02569398.
- atabecestat (JNJ-54861911) / J&J
Sensitivity of the Preclinical Alzheimer’s Cognitive Composite (PACC), PACC5, and Repeatable Battery for Neuropsychological Status (RBANS) to Amyloid Status in Preclinical Alzheimer Disease -Atabecestat Phase 2b/3 EARLY Clinical Trial () - Oct 16, 2021 - Abstract #CTAD2021CTAD_244;
The Aβ+/− group effect was statistically larger for PACC and marginally larger for PACC5 as compared with the RBANS. However, interpretation of composite sensitivity to Aβ status cross-sectionally cannot be generalized to sensitivity to change over time.
- || Review, Journal: Selective Secretase Targeting for Alzheimer's Disease Therapy. (Pubmed Central) - Sep 17, 2021
Such therapeutic tools shall focus on slowing down or minimizing the progression of neuronal damage. Here, we summarize structures and the activities of the latest compounds designed for AD treatment, with remarkable in vitro, in vivo, and clinical phase activities.
- | Review, Journal: BACE1 inhibitors: Current status and future directions in treating Alzheimer's disease. (Pubmed Central) - Jul 9, 2021
Furthermore, the review demonstrates with increasing evidence that despite tremendous efforts and promising results conceived with BACE1 inhibitors, the latest studies suggest that their clinical use for treating Alzheimer's disease should be reconsidered. Finally, the review sheds light on alternative therapeutic options for targeting AD.
- || atabecestat (JNJ-54861911) / J&J
Clinical, Journal: Drug-specific T-cell responses in patients with liver injury following treatment with the BACE inhibitor atabecestat. (Pubmed Central) - Jun 30, 2021
Finally, the review sheds light on alternative therapeutic options for targeting AD. The detection of atabecestat metabolite-responsive T-cell clones activated via a pharmacological interactions pathway in patients with liver injury is indicative of an immune-based mechanism for the observed hepatic enzyme elevations.
- || atabecestat (JNJ-54861911) / J&J
Clinical, Journal: Long-term safety and tolerability of atabecestat (JNJ-54861911), an oral BACE1 inhibitor, in early Alzheimer's disease spectrum patients: a randomized, double-blind, placebo-controlled study and a two-period extension study. (Pubmed Central) - Jun 26, 2021
P2, P2a
The detection of atabecestat metabolite-responsive T-cell clones activated via a pharmacological interactions pathway in patients with liver injury is indicative of an immune-based mechanism for the observed hepatic enzyme elevations. Atabecestat was associated with trend toward declines in cognition, and elevation of liver enzymes.
- || atabecestat (JNJ-54861911) / J&J
Clinical, Journal: Biopsy pathology and immunohistochemistry of a case of immune-mediated drug-induced liver injury with Atabecestat. (Pubmed Central) - Jun 22, 2021
The time-course of these elevations was heterogenous; values often normalized while on treatment, though in some cases they continued to rise after treatment was stopped. In all cases the abnormalities eventually resolved.
- ||| https://t.co/2kmoEtPV2I and after semagacestat, bapineuzumab, solanezumab, gantenerumab, crenezumab, verubecestat, lanabecestat, atabecestat, umibecestat, & elenbecestat had ALL failed to prove the amyloid-beta hypothesis. Stunning. (Twitter) - Jun 9, 2021
- |||| atabecestat (JNJ-54861911) / J&J, umibecestat (CNP520) / Novartis, Amgen, Banner Alzheimer’s Institute, solanezumab (LY2062430) / Eli Lilly
Clinical: (6/6) How many have already been tested in healthy people with brain amyloid ("Alzheimer's continuum")? 3. –Umibecestat, Solanezumab, and Atabecestat. Of the 2 with data available, those on placebo remained healthy; on the anti-amyloid drug became cognitively impaired. (Twitter) - Jun 9, 2021
- ||| Clinical: (4/6) How many worsened cognition compared to placebo? 7 –Semagacestat, Avagacestat, Verubecestat, Atabecestat, Lanabecestat, Umibecestat, and Donanemab. The others were truly futile. (Twitter) - Jun 9, 2021
- || (3/6) These are: Semagacestat, Avagacestat, Solanezumab, CAD106, Crenezumab, Gantenerumab, Avagacestat, Verubecestat, Atabecestat, Lanabecestat, Crenezumab, Elenbecestat, Umibecestat, Donanemab. (Twitter) - Jun 9, 2021
- ||| atabecestat (JNJ-54861911) / J&J
Clinical, P2/3 data, P2b data, Clinical Trial,Phase II, Journal: Discovery of Atabecestat (JNJ-54861911): A Thiazine-Based β-Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor Advanced to the Phase 2b/3 EARLY Clinical Trial. (Pubmed Central) - May 5, 2021
The potential of reactive metabolite formation was evaluated in a covalent binding study to assess its irreversible binding to human hepatocytes. Unfortunately, the EARLY trial was discontinued due to significant elevation of liver enzymes, and subsequent analysis of the clinical outcomes showed dose-related cognitive worsening.
- || atabecestat (JNJ-54861911) / J&J
Interesante reflexión sobre #atabecestat del @AlbertoEspay (Twitter) - Mar 21, 2021
- ||||| atabecestat (JNJ-54861911) / J&J
Clinical: (5/10) The trial was discontinued in May 2018 ostensibly because of liver toxicity. Even truncated, the changes were opposite to those predicted: individuals on placebo remained cognitively normal, those on atabecestat experienced cognitive worsening. https://t.co/yvKkOdWP0o (Twitter) - Mar 21, 2021
- ||| atabecestat (JNJ-54861911) / J&J
Clinical: (4/10) Healthy participants without symptoms but with high brain amyloid were randomized (1:1:1) to once-daily atabecestat 10 mg, 25 mg, or placebo, with prespecified clinical CSF, and MRI assessments every 6 months for up to 54 months. (Twitter) - Mar 21, 2021
- |||| atabecestat (JNJ-54861911) / J&J
P2/3 data, P2b data: (3/10) That’s the gap the phase 2b/3 EARLY trial (NCT02569398) of atabecestat was meant to bridge: slow the onset of cognitive decline in people without cognitive symptoms but at risk of AD by virtue of high brain amyloid --those in the “AD continuum” in the scientific narrative. (Twitter) - Mar 21, 2021
P2b
- |||| atabecestat (JNJ-54861911) / J&J
A tale for our times. What the story of #atabecestat, a BACE inhibitor being rescued from its ruins, tell us about our love affair with the #amyloid hypothesis. A 10-part thread. #Alzheimers @JAMANeuro @alzassociation @alzforum @alzfdn #BrainFables (Twitter) - Mar 21, 2021
- || atabecestat (JNJ-54861911) / J&J
Cognitive Effects Transient for Alzheimer's Drug Atabecestat https://t.co/qyz9gxhpOV via @medscape (Twitter) - Feb 5, 2021
- | atabecestat (JNJ-54861911) / J&J
Trial termination: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (clinicaltrials.gov) - Feb 10, 2020
P2b, N=557, Terminated, Sponsor: Janssen Research & Development, LLC
Unfortunately, the EARLY trial was discontinued due to significant elevation of liver enzymes, and subsequent analysis of the clinical outcomes showed dose-related cognitive worsening. Completed --> Terminated; Change in benefit-risk profile for individuals with early sporadic Alzheimer Disease because of elevations in liver enzymes in subjects receiving atabecestat
- atabecestat (JNJ-54861911) / J&J, solanezumab (LY2062430) / Eli Lilly
UT POINTS FOR COGNITIVE DECLINE USING MMSE DEFINE BASELINE AND LONGITUDINAL DIFFERENCES IN BOTH CLINICAL AND PATHOLOGICAL ALZHEIMER’S DISEASE BIOMARKERS. () - Dec 13, 2019 - Abstract #CTAD2019CTAD_337;
P=N/A, P2b
The CPSS will provide a head-to-head comparison of the rate of change in 2 cognitive outcomes proposed for use in therapeutic trials of preclinical AD. While cross-sectional comparisons may not be predictive of longitudinal changes, lower values on both scales for the amyloid positive individuals indicate a potential sensitivity to the impact of Alzheimer’s pathology in this cohort.
- | atabecestat (JNJ-54861911) / J&J, Avelox (moxifloxacin) / Bayer
Retrospective data, Journal: Evaluating Potential QT Effects of JNJ-54861911, a BACE Inhibitor in Single- and Multiple-Ascending Dose Studies, and a Thorough QT Trial With Additional Retrospective Confirmation, Using Concentration-QTc Analysis. (Pubmed Central) - Nov 30, 2019
Provided sufficiently high plasma concentrations were captured, mild QT prolongation observed postdose with a supratherapeutic dose could be detected (TQT study) and estimated in SAD/MAD studies. Based on population pharmacokinetic modeling and simulation, 5 and 25 mg doses are currently considered for further phase 3 studies and are expected not to cause any relevant QT prolongation.
- ALZHEIMER’S PREVENTION INITIATIVE GENERATION PROGRAM: UPDATE AND NEXT STEPS () - Oct 16, 2019 - Abstract #CTAD2019CTAD_60;
Results from the Generation Program will be analyzed including follow-up visits o -treatment to evaluate the potential reversal of the observed early worsening of cognitive measures. Trial findings, data, biological samples, and motivated amyloid-positive and -negative participants will provide important resources for the advancement of AD prevention research.
- | atabecestat (JNJ-54861911) / J&J
Biomarker, Clinical, PK/PD data, Journal: Pharmacodynamics of atabecestat (JNJ-54861911), an oral BACE1 inhibitor in patients with early Alzheimer's disease: randomized, double-blind, placebo-controlled study. (Pubmed Central) - Sep 11, 2019
P1
Trial findings, data, biological samples, and motivated amyloid-positive and -negative participants will provide important resources for the advancement of AD prevention research. JNJ-54861911 at 10 and 50 mg daily doses after 4 weeks resulted in mean CSF Aβ reductions of 67% and up to 90% in both Caucasian and Japanese patients with early stage AD, confirming results in healthy elderly adults.
- | atabecestat (JNJ-54861911) / J&J
Journal: Preliminary Results of a Trial of Atabecestat in Preclinical Alzheimer's Disease. (Pubmed Central) - Apr 19, 2019
JNJ-54861911 at 10 and 50 mg daily doses after 4 weeks resulted in mean CSF Aβ reductions of 67% and up to 90% in both Caucasian and Japanese patients with early stage AD, confirming results in healthy elderly adults. No abstract available
- || atabecestat (JNJ-54861911) / J&J
Atabecestat does not appear to help either! (Twitter) - Apr 11, 2019
- | atabecestat (JNJ-54861911) / J&J
Trial completion, Enrollment change, Trial completion date, Trial primary completion date: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (clinicaltrials.gov) - Jan 22, 2019
P2b, N=596, Completed, Sponsor: Janssen Research & Development, LLC
No abstract available Active, not recruiting --> Completed | N=1650 --> 596 | Trial completion date: Apr 2024 --> Dec 2018 | Trial primary completion date: Apr 2024 --> Dec 2018
- | atabecestat (JNJ-54861911) / J&J
Trial termination: An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum (clinicaltrials.gov) - Nov 15, 2018
P2, N=90, Terminated, Sponsor: Janssen Research & Development, LLC
Active, not recruiting --> Completed | N=1650 --> 596 | Trial completion date: Apr 2024 --> Dec 2018 | Trial primary completion date: Apr 2024 --> Dec 2018 Completed --> Terminated
- | atabecestat (JNJ-54861911) / J&J
Trial completion, Trial completion date, Trial primary completion date: An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum (clinicaltrials.gov) - Sep 7, 2018
P2, N=90, Completed, Sponsor: Janssen Research & Development, LLC
Completed --> Terminated Active, not recruiting --> Completed | Trial completion date: Oct 2022 --> Jun 2018 | Trial primary completion date: Oct 2022 --> Jun 2018
- | atabecestat (JNJ-54861911) / J&J
Trial completion: Characterization of T-Cell Response in Participants Previously Treated With JNJ-54861911 (Atabecestat) (clinicaltrials.gov) - Aug 28, 2018
P1, N=9, Completed, Sponsor: Janssen Research & Development, LLC
Active, not recruiting --> Completed | Trial completion date: Oct 2022 --> Jun 2018 | Trial primary completion date: Oct 2022 --> Jun 2018 Recruiting --> Completed
- | atabecestat (JNJ-54861911) / J&J
New P1 trial: Characterization of T-Cell Response in Participants Previously Treated With JNJ-54861911 (Atabecestat) (clinicaltrials.gov) - Jul 15, 2018
P1, N=9, Recruiting, Sponsor: Janssen Research & Development, LLC
- ||| atabecestat (JNJ-54861911) / J&J
Enrollment closed: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (clinicaltrials.gov) - Jun 1, 2018
P2b, N=1650, Active, not recruiting, Sponsor: Janssen Research & Development, LLC
Recruiting --> Completed Recruiting --> Active, not recruiting
- || atabecestat (JNJ-54861911) / J&J
Trial primary completion date: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (clinicaltrials.gov) - Aug 28, 2017
P2b, N=1650, Recruiting, Sponsor: Janssen Research & Development, LLC
Recruiting --> Active, not recruiting Trial primary completion date: Apr 2023 --> Apr 2024
- atabecestat (JNJ-54861911) / J&J
Enrollment change: A Pharmacokinetic Interaction Study Between JNJ-54861911 and Transporter Substrates Rosuvastatin and Metformin in Healthy Participants (clinicaltrials.gov) - Aug 22, 2017
P1, N=32, Completed, Sponsor: Janssen Research & Development, LLC
Trial primary completion date: Apr 2023 --> Apr 2024 N=61 --> 32
- ||| atabecestat (JNJ-54861911) / J&J
Enrollment closed: An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum (clinicaltrials.gov) - Nov 28, 2016
P2, N=90, Active, not recruiting, Sponsor: Janssen Research & Development, LLC
N=61 --> 32 Recruiting --> Active, not recruiting
- || atabecestat (JNJ-54861911) / J&J
Trial primary completion date: An Extension Study to Evaluate the Long-Term Safety and Tolerability of JNJ-54861911 in Participants in the Early Alzheimer's Disease Spectrum (clinicaltrials.gov) - Sep 7, 2016
P2, N=100, Recruiting, Sponsor: Janssen Research & Development, LLC
Recruiting --> Active, not recruiting Trial primary completion date: Feb 2024 --> Oct 2022
- ||| atabecestat (JNJ-54861911) / J&J
Trial completion, Enrollment change: A Pharmacokinetic Interaction Study Between JNJ-54861911 and Transporter Substrates Rosuvastatin and Metformin in Healthy Participants (clinicaltrials.gov) - Aug 23, 2016
P1, N=61, Completed, Sponsor: Janssen Research & Development, LLC
Trial primary completion date: Feb 2024 --> Oct 2022 Recruiting --> Completed | N=32 --> 61
- |||| atabecestat (JNJ-54861911) / J&J
Trial completion, Phase classification: A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - Jul 12, 2016
P2a, N=114, Completed, Sponsor: Janssen Research & Development, LLC
Recruiting --> Completed | N=32 --> 61 Active, not recruiting --> Completed | Phase classification: P2 --> P2a
- | atabecestat (JNJ-54861911) / J&J
Phase classification: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (clinicaltrials.gov) - Jun 15, 2016
P2b, N=1650, Recruiting, Sponsor: Janssen Research & Development, LLC
Active, not recruiting --> Completed | Phase classification: P2 --> P2a Phase classification: P2/3 --> P2b
- atabecestat (JNJ-54861911) / J&J
Enrollment open: A Pharmacokinetic Interaction Study Between JNJ-54861911 and Transporter Substrates Rosuvastatin and Metformin in Healthy Participants (clinicaltrials.gov) - Apr 22, 2016
P1, N=32, Recruiting, Sponsor: Janssen Research & Development, LLC
Phase classification: P2/3 --> P2b Not yet recruiting --> Recruiting
- | atabecestat (JNJ-54861911) / J&J
Trial completion, Trial primary completion date: Study Investigating the Effects of JNJ-54861911 on Amyloid-beta Processing in Cerebrospinal Fluid (CSF) and Plasma in Japanese Participants Asymptomatic at Risk for Alzheimer Dementia (clinicaltrials.gov) - Jan 25, 2016
P1, N=18, Completed, Sponsor: Janssen Pharmaceutical K.K.
Not yet recruiting --> Recruiting Active, not recruiting --> Completed | Trial primary completion date: Dec 2015 --> Sep 2015
- || atabecestat (JNJ-54861911) / J&J
Trial primary completion date: A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - Jan 21, 2016
P2, N=114, Active, not recruiting, Sponsor: Janssen Research & Development, LLC
Active, not recruiting --> Completed | Trial primary completion date: Dec 2015 --> Sep 2015 Trial primary completion date: Dec 2015 --> Jun 2016
- ||| atabecestat (JNJ-54861911) / J&J
Enrollment closed: A Safety and Tolerability Study of JNJ-54861911 in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - Dec 21, 2015
P2, N=114, Active, not recruiting, Sponsor: Janssen Research & Development, LLC
Trial primary completion date: Dec 2015 --> Jun 2016 Recruiting --> Active, not recruiting
- |||||| atabecestat (JNJ-54861911) / J&J
Enrollment open: An Efficacy and Safety Study of Atabecestat in Participants Who Are Asymptomatic at Risk for Developing Alzheimer's Dementia (clinicaltrials.gov) - Dec 9, 2015
P2/3, N=1650, Recruiting, Sponsor: Janssen Research & Development, LLC
Recruiting --> Active, not recruiting Not yet recruiting --> Recruiting
- | atabecestat (JNJ-54861911) / J&J
New P1 trial: A Pharmacokinetic Interaction Study Between JNJ-54861911 and Transporter Substrates Rosuvastatin and Metformin in Healthy Participants (clinicaltrials.gov) - Nov 21, 2015
P1, N=32, Not yet recruiting, Sponsor: Janssen Research & Development, LLC