This trial, CREAD2, will complement the current randomized, double-blind, placebo-controlled, parallel group Phase 3 clinical trial (CREAD1, NCT02670083).
CREAD1 is evaluating the effectiveness and safety of crenezumab versus a placebo in 750 participants with early to mild AD. Participants are being randomly assigned to receive an intravenous dose of crenezumab or a placebo every four weeks for 100 weeks.
The study’s final effectiveness and safety assessment will occur 52 weeks after the last crenezumab dose.
CREAD1 is expected to run until 2020. Investigators will evaluate any changes in participants’ dementia rating and their performance on neuropsychological tests.
More details about the CREAD2 trial design, which will include the same number of participants, will be announced soon.
“We are delighted with the strong commitment of our partner Genentech to developing crenezumab as a potential disease-modifying therapy for Alzheimer’s,” Professor Andrea Pfeifer, CEO of AC Immune, said in a press release. “Given the recent disappointing results of other therapies, all of us in the Alzheimer’s community need to redouble our efforts to combat one of society’s biggest challenges. We remain confident about the potential of crenezumab given it is distinct from other beta amyloid antibodies, predominantly blocking oligomers in the brain, and has a clinical development program that is using higher dosing and targeting earlier stages of Alzheimer’s disease.”
Crenezumab is a passive immunotherapy that involves patients being treated with monoclonal antibodies that recognize amyloid-β (Aβ) proteins. Accumulation of amyloid-β proteins and amyloid plaque in the brain are central to the development of Alzheimer’s.
AC Immune used its SupraAntigen technology to engineer crenezumab to recognize multiple forms of aggregated Aβ peptides. It licensed the therapy to Genentech in 2006. Crenezumab eliminates excess Abeta peptides while having little impact on microglia, immune cells in the central nervous system.
Phase 1 safety trials in healthy volunteers (NCT02427243) and Alzheimer’s patients (NCT02353598) offered no evidence that crenezumab led to vasogenic edema or cerebral microhemorrhage. Those findings allowed the Phase 2 studies (NCT01723826) and (NCT01998841) to use higher doses (60 mg/kg) and achieve higher brain exposure than was possible with previous immunotherapy approaches.
Genentech used the Phase 2 results to develop a drug-disease progression model to predict the impact that higher doses would have on patients in the Phase 3 trials.
The company made a presentation about crenezumab’s unique mode of action and its increased-dosing plans at the 9th Clinical Trials on Alzheimer’s disease Conference in San Diego in December 2016.