Cogstate tests were used in the Phase 1, 2-period crossover study of intranasal esketamine to evaluate any potential cognitive effects. Subjects were tested multiple times in short succession. At 40-minutes post-dose there was a significant difference in cognition from placebo, and at 2-hours post-dose no significant difference in cognition was found between groups. This cognitive safety data contributed to the Risk Evaluation and Mitigation Strategy (REMS) of intranasal esketamine. (Bahr, R., et al., Pharmacy and Therapeutics, 2019: PMCID: PMC6534172)
Case Studies of Digital Assessments in Action
Cogstate digital assessments have been leveraged across all phases of clinical trials to help research teams answer critical study questions around safety and efficacy. Data from the tests have been seen and accepted by regulators. Tests are effective and equivalent when deployed inside or outside the clinical site (remote). The following case studies represent only a handful of the many ways our digital cognitive assessments are leveraged.
Ph 1 Cognitive Safety and REMS
Patient Selection and Enrollment for Ph 3 Global Program
The Cogstate International Shopping List test (ISLT) was used to select appropriate patients for the global Phase 3 MissionAD studies investigating the BACE inhibitor elenbecestat. More than 8,000 adults were screened for entry, and the research team fully enrolled their trials. Data showed the ability of the ISLT to confirm a clinically important memory impairment. (Albala, et al, CTAD 2017)
Pivotal Ph 3 Safety Evaluation and Regulatory Approval
Four Cogstate tests were selected as safety outcomes for a pivotal, international Phase 3 pediatric trial of repatha, a drug to address hypercholesteremia. Cholesterol is important for the brain, so it was necessary to show the scientific community and regulators that the drug did not cause any problem with thinking. Data demonstrated that the drug reduced cholesterol levels and is safe in its effect on the brain. The FDA approved the drug for children aged 10+. (R.D. Santos et al., NEJM: DOI 10.1056/NEJMoa2019910)
Support for Proof-of-Concept Evidence Generation in Phase 2 Studies Exploring Cognition
Cogstate digital tests have been used in multiple clinical trials to demonstrate Proof of Concept (POC) and generate efficacy data and support go/no-go decisions in relation to cognition.
- Cogstate digital assessments were used as exploratory efficacy endpoints in a Ph 2 study of PQ912 in Alzheimer’s disease. Data indicated a treatment-related improvement in working memory, helping guide the team into future study questions and considerations regarding the impact of PQ912. (Scheltens et al. Alzheimer’s Research & Therapy (2018) 10:107)
- A phase 2 study of Encenicline for Cognitive Impairment Associated with Schizophrenia (CIAS) was designed to assess and characterize treatment effect on cognition. A Cogstate digital battery was selected as the primary efficacy endpoint. Notable improvements in cognition were demonstrated for treatment vs placebo. (Keefe et al Neuropsychopharmacology (2015) 40, 3053-3060.)
- A paper in Drug Discovery Today—co-authored by two Cogstate scientists—noted how cognitive data can be used for better Go/No-Go decision-making in Alzheimer’s clinical trials and explored how to apply robust decision-making criteria depending on the specific stage of development, mechanism of action, and design of the trial. Read more.