Implementation of a Validated Research-Use Plasma pTau217 Assay in the Participant Screening Process for the Phase 2 ALTITUDE-AD Study of Sabirnetug
The ALTITUDE-AD study is a Phase 2 trial investigating the efficacy and safety of sabirnetug, an investigational Alzheimer’s disease (AD) treatment, developed by AC Immune SA. This trial employs a rigorous participant screening process to ensure the selection of suitable candidates. One of the essential biomarkers used in the screening process is tau protein, specifically pTau217, which plays a crucial role in neurofibrillary tangles, a hallmark of AD. In this blog post, we will discuss the implementation of a validated research-use plasma pTau217 assay in the participant screening process for the Phase 2 ALTITUDE-AD study.
Background
Tau protein is a microtubule-associated protein that plays a critical role in maintaining the stability of microtubules in neurons. In AD, tau proteins undergo hyperphosphorylation, leading to the formation of neurofibrillary tangles and eventual neuronal damage. pTau217 is one of the phosphorylated tau isoforms, and its levels are elevated in the cerebrospinal fluid and plasma of AD patients. Therefore, pTau217 is a promising biomarker for AD diagnosis and disease progression.
Implementation of the pTau217 Assay
The pTau217 assay is a sandwich enzyme-linked immunosorbent assay (ELISA) that measures the concentration of pTau217 in plasma. The assay was validated according to the European Medicines Agency (EMA) guidelines for in vitro diagnostic medical devices (IVDs). The validation process included assessing the analytical performance, clinical performance, and precision of the assay.
Analytical Performance
The analytical performance of the assay was evaluated by measuring the accuracy, precision, and linearity of the assay. The accuracy was demonstrated by comparing the results obtained with the pTau217 assay to those obtained with a validated, independent method, showing a good agreement between the two methods. The precision of the assay was assessed by measuring the within-run and between-run variability, which were found to be acceptable.
Clinical Performance
The clinical performance of the assay was assessed by comparing the pTau217 levels in plasma samples from healthy controls and AD patients. The results showed a significant difference in pTau217 levels between the two groups, with higher levels in the AD patients. The assay’s sensitivity and specificity were also evaluated, and the results demonstrated that the pTau217 assay can accurately distinguish between AD patients and healthy controls.
Precision
The precision of the assay was evaluated by analyzing the within-run and between-run variability. The results showed that the assay had acceptable precision, with coefficients of variation (CVs) below 10% for both within-run and between-run measurements.
Impact on Individuals and Society
The implementation of the validated research-use plasma pTau217 assay in the participant screening process for the Phase 2 ALTITUDE-AD study will have significant implications for individuals and society. For individuals, the assay will help identify those who may benefit from participating in clinical trials, thereby increasing the chances of finding effective treatments for AD. It will also provide valuable information about their disease status, which can help guide their clinical management and treatment decisions.
For society, the implementation of the pTau217 assay in clinical trials can lead to a more efficient and effective drug development process. By identifying suitable candidates more quickly and accurately, the time and resources required for clinical trials can be reduced, ultimately leading to the faster availability of new treatments for AD. Furthermore, the use of biomarkers like pTau217 can help improve our understanding of the disease mechanism and progression, leading to new insights into the disease and potential new therapeutic targets.
Conclusion
In conclusion, the implementation of a validated research-use plasma pTau217 assay in the participant screening process for the Phase 2 ALTITUDE-AD study is a significant step forward in the development of effective treatments for Alzheimer’s disease. The assay’s analytical and clinical performance, as well as its precision, have been demonstrated, making it a valuable tool for identifying suitable candidates for clinical trials and guiding clinical management. The use of this assay in clinical trials can lead to a more efficient and effective drug development process, ultimately benefiting individuals and society as a whole. As research in the field of AD continues to advance, the role of biomarkers like pTau217 will become increasingly important, and the use of validated assays like the pTau217 assay will become essential for ensuring the success of clinical trials and the development of new treatments for AD.
- AC Immune SA is conducting a Phase 2 trial, ALTITUDE-AD, to evaluate the efficacy and safety of sabirnetug for Alzheimer’s disease.
- The trial employs a rigorous participant screening process that includes the measurement of pTau217 in plasma using a validated research-use assay.
- pTau217 is a promising biomarker for AD diagnosis and disease progression.
- The pTau217 assay was validated according to EMA guidelines for IVDs.
- The implementation of the pTau217 assay in the participant screening process will lead to more efficient and effective clinical trials, ultimately benefiting individuals and society as a whole.
