According to Roche's pipeline as at October 2014, regulatory filings for crenezumab in treatment of Alzheimer's disease are expected post 2017.
In May 2019, Roche completed the phase III CREAD OLE trial, long-term extension of phase III studies (BN29552/BN29553) [see below], which evaluated the safety and efficacy patients on of long-term crenezumab IV infusion in patients with Alzheimer's disease (BN40031; EudraCT2017-002702-12; NCT03491150). The open-label study that was initiated in April 2018 enrolled 149 patients in Australia, Canada, Finland, France, Germany, Hong Kong, Italy, South Korea, Lithuania, Mexico, Poland, Russia, Spain, Turkey, Ukraine, the UK and the US  .
Genentech, in January 2019 discontinued its phase III CREAD 1 trial of crenezumab that evaluated efficacy and safety of crenezumab IV infusion in participants with prodromal-to-mild Alzheimer's disease (BN29552; NCT02670083). The decision resulted from the recommendation of an independent Data Safety Monitoring Board (DSMB), based on a pre-planned interim analysis of efficacy and safety, which indicated that crenezumab was unlikely to meet the primary endpoint of change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score baseline to week 105. The randomised, double-blind, placebo-controlled trial was initiated in March 2016, enrolled 813 patients in the US, Australia, Austria, Belgium, Bulgaria, Canada, Costa Rica, Croatia, the Czech Republic, Denmark, Finland, France, Germany, Hong Kong, Hungary, Italy, South Korea, Lithuania, Mexico, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine and the UK. Earlier, the recruitment in the trial was completed in the fourth quarter of 2017. In February 2017, the company reported that results from a phase Ib dose-escalation study and an exposure-response model supports the 60mg/kg dose in the trial.       .
Genentech, in January 2019 discontinued its phase III CREAD 2 trial of crenezumab that evaluated efficacy and safety of crenezumab IV infusion in participants with prodromal-to-mild Alzheimer's disease (BN29553; EudraCT2016-003288-20; NCT03114657).The decision resulted from the recommendation of an independent Data Safety Monitoring Board (DSMB), based on a pre-planned interim analysis of efficacy and safety, which indicated that crenezumab was unlikely to meet the primary endpoint of change from baseline in Clinical Dementia Rating-Sum of Boxes (CDR-SB) Score. Earlier, recruitment in the trial was completed in July 2018.The randomised, double-blind, placebo-controlled trial was initiated in March 2017 and enrolled 750 patients across Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Estonia, France, Germany, Israel, Italy, Japan, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Russia, Serbia, Slovakia, South Africa, Spain, Taiwan, Turkey, United Kingdom and the US    .
In June 2019, Genentech initiated a phase II trial to evaluate the effect of crenezumab on the longitudinal tau burden in a subgroup of preclinical Presenilin1 (PSEN1) E280A mutation carriers and non-carriers, who were enrolled in study NCT01998841 (GN28352) (NCT03977584; BN40199). Participants will receive up to three intravenous (IV) injections of [^18F] Genentech Tau Probe 1 (GTP1) and will undergo a tau positron emission tomography (PET) scan after each IV injection of [18^F]GTP1. The purpose of this substudy is to increase the understanding of disease progression in the preclinical stage of familial Alzheimer's Disease (AD). The double-blind, randomised trial is enrolling approximately 150 patients in the US   .
In November 2013, Genentech initiated a phase II clinical trial to investigate the efficacy of crenezumab SC for the prevention of Alzheimer's disease in cognitively healthy participants who have a genetic predisposition to develop the disease (NCT01998841; GN28352). Shortly afterward, in December 2013, the first drug doses were administered to study participants. The double-blind trial is recruiting approximately 300 participants, aged 30-60 years, from a large extended family in Colombia who have a genetic mutation that typically leads to the early onset of Alzheimer's disease symptoms. A small number of patients from the US will also be recruited. Participants will receive crenezumab injections SC at two-weekly intervals for up to five years. The trial will also include relatives who are non-carriers of the mutation; these individuals will receive placebo. The effects of crenezumab on the accumulation of amyloid and other key proteins are being evaluated using imaging techniques, cerebrospinal fluid tests and cognitive measures, including cognitive function. In May 2012, the landmark trial was announced by the Alzheimer's Prevention Initiative (API), which is an international collaboration involving Genentech, the US National Institutes of Health (NIH), the Banner Alzheimer′s Institute (BAI), and the University of Antioquia in Colombia. The $US100 million study is funded primarily by Genentech, and by a 5-year $US16 million grant from the US NIH, and a $US15 million grant from the BAI   . PRA, a clinical research organisation, announced its participation in this trial in July 2012  . The trial is expected to end in 2020; study results will be released soon after  .
In February 2017, Genentech completed a long-term safety and tolerability extension phase II trial of crenezumab in patients with mild to moderate Alzheimer's disease and who participated in and completed the BLAZE or ABBY trials (EudraCT2012-003242-33; NCT01723826; UKCRN13360; DeNDRoN066ext; GN28525). The trial was initiated in November 2012 and enrolled 360 patients in the US, Canada, France, Germany, Spain and the UK  .
Genentech completed the phase II BLAZE biomarker trial of crenezumab in patients with Alzheimer's disease in April 2014 (ABE4955g; NCT01397578). The primary endpoint of the trial was the change in brain amyloid load from baseline to week 69. The trial recruited 91 patients at sites in the US, France and Spain. The company reported data from this trial at the Alzheimer's Association International Conference (AAIC-2014)   . The pooled analysis results from the ABBY and BLAZE phase II trials were presented at the Alzheimer's Association International Conference (AAIC-2018)   .
In February 2014, Genentech completed the randomised, double-blind, placebo-controlled phase II ABBY trial that assessed the safety and efficacy of intravenous and subcutaneous formulations of crenezumab in patients with mild to moderate Alzheimer's disease (ABE4869g; NCT01343966). This 73-week trial enrolled 450 patients at sites in the US, Canada, France, Germany, Spain and the UK. Initiation of the trial triggered a milestone payment to AC Immune. In July 2014, the company reported that the trial failed to meet its co-primary endpoints and these data were presented at the Alzheimer's Association International Conference (AAIC-2014)   .
In March 2016, Chugai Pharmaceutical initiated a long-term phase I trial to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of crenezumab IV infusion in patients with Alzheimer's disease (JapicCTI-163210). The placebo-controlled trial will enrol approximately eight patients in Japan  .
In June 2017, Genentech completed a phase Ib trial that investigated the safety and tolerability of intravenous crenezumab, in patients with mild to moderate Alzheimer's disease (GN29632; NCT02353598). The randomised, placebo-controlled, double-blind, trial was initiated in January 2015, and enrolled 77 patients in the US  . In December 2016, results from the trial were reported by the company. These safety and pharmacokinetic data of the study support the continued treatment of patients with crenezumab at a higher dose of 60mg/kg. An optional open-label extension portion, after completion of the double blind portion of the study, will be offered to patients  .
In July 2015, Genentech completed a phase I trial that assessed the relative bioavailability and tolerability of two formulations of crenezumab in healthy volunteers following subcutaneous administration (GP29172, NCT02427243). The single-dose, randomised, open-label, parallel group study was initiated in April 2015, that enrolled 60 volunteers in the US  .
Genentech completed a phase I trial of crenezumab in patients with mild-to-moderate AD in May 2010 (ABACUS; NCT00736775). The trial included 56 subjects, who were recruited at several sites throughout the US. Crenezumab was given as single and multiple IV doses. The enrolment of the first patient in the phase I trial triggered a milestone payment of an undisclosed amount to AC Immune by Genentech   .
In May 2010, Genentech completed a phase I trial of subcutaneous and intravenous formulations of crenezumab in healthy subjects in the US (NCT00997919). The trial evaluated the safety, tolerability, pharmacokinetics and bioavailability of single doses of the drug  .
In October 2018, AC Immune released in vitro data that underscored the clinical rationale for crenezumab, as a potential therapy for treating Alzheimer's disease  .