Therapy Type: Immunotherapy (passive) (timeline)
Target Type: Tau (timeline), Unknown
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Eli Lilly & Co.
Derived from the mouse monoclonal antibody MCI-1, LY3303560 is a humanized anti-tau antibody that binds and neutralizes soluble tau aggregates. At the 2017 AAIC meeting, Lilly presented data from surface plasmon resonance binding and ELISA assays to assess LY3303560's selectivity to aggregates over monomer and characterize its epitope. LY3303560 reportedly had high affinity to soluble tau aggregate in vitro, at a KD of below 220 picomolar, compared to monomer, KD of 235 nanomolar. The antibody reportedly recognizes a conformational epitope whose primary epitope is in tau's N-terminal region. Intravenous administration to monkeys indicated clearance of 0.15 ml/h/kg and a half-life of 13 days. SC administration indicated a bioavailability of 79 percent, and rat CSF concentration was 0.1 percent of plasma at 24 hours after IV administration (Alam et al., 2017).
In April 2016, Lilly started a first-in-human trial of LY3303560 in 110 people, both healthy volunteers and people whose MCI due to AD or mild to moderate AD was ascertained with a positive amyloid PET scan. This study evaluated a single, escalating intravenous infusion or subcutaneous injection of LY3303560 or placebo. It measures adverse effects up to 85 days after this dose, as well as exposure and maximal achieve drug concentration in both serum and CSF. This study requires a four-day stay in a clinical research unit and 10 follow-up visits. It is being conducted in California and Maryland.
In January 2017, a second Phase 1 study started enrolling 24 people with the same diagnosis for an escalating-multiple-dose study of intravenously delivered LY3303560 or placebo. It will last six months plus four months follow-up, and measure adverse events and pharmacokinetic parameters. Notably, this trials infuses LY3303560 or placebo, and amyloid and tau PET tracers, in the same session. This trial engages 12 sites in the U.S., the U.K., and Japan, and will run until June 2019.
In April 2018, Phase 2 began with a first efficacy trial enrolling 285 people who have had a gradual and progressive decline in memory for at least six months. The study will compare two intravenous doses to placebo, though the treatment regimen and duration had not been disclosed as of May 16, 2018. Change from baseline on Lilly's integrated Alzheimer's Disease Rating Scale (iADRS) is the primary outcome; secondary measures include ADAS-Cog13, ADCS-iADL, CDR-SB, MMSE, the CogState Brief Battery (CBB), as well as tau PET, volumetric MRI, the Columbia Suicide Severity Rating Scale (C-SSRS), and antigenicity of LY3303560. This trial will run at 60 sites in North America and Japan, until October 2021.
For all trials, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 2
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
|Eli Lilly & Co.||NCT03518073||
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