PRECEPT: CEP-1347

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

The Parkinson Study Group, sponsored by Cephalon (with Lundbeck, per FDAnews). Neurology 2007;69:1480. Registered as NCT00040404 (registry phase: 2/3; terminated, reason given: "Unlikely to provide evidence of significant effect"). The trial ran from April 2002 to August 2005; the paper came out in 2007.

What happened

CEP-1347 blocks mixed-lineage kinases, enzymes that switch on a cell-death pathway (apoptosis, "programmed cell death"). It enhanced neuron survival in a range of non-clinical models (MPTP, landmark 2, is the standard Parkinson's toxin model) and was safe and well tolerated in a 4-week human test.

• Design. 806 people with early Parkinson's, not yet needing dopamine treatment, randomised to CEP-1347 10, 25 or 50 mg twice a day, or placebo. The main measure was time until disability required dopamine treatment, the endpoint used in DATATOP (landmark 61).
• Result. Stopped after an average of 21.4 months at a planned interim analysis. 57% of placebo people (108/191) had reached the endpoint, versus 65% (133/205) on 10 mg, 59% (126/212) on 25 mg and 64% (127/198) on 50 mg. UPDRS and β-CIT scans looked the same.

Why it moved us toward a cure

It was the largest neuroprotection trial of an anti-apoptotic idea, and it failed despite good animal data. The authors stressed the gap between animal prediction and human outcome. Blood samples from PRECEPT also fed the urate finding in landmark 131.

Outcome

Dead end. The trial was stopped for futility. The sources read do not say what happened to the programme.

Sources

• Parkinson Study Group, Neurology 2007;69:1480, doi:10.1212/01.wnl.0000277648.63931.c0 · PubMed 17881719
• FDAnews, trial discontinued
• Schwarzschild et al., Arch Neurol 2008;65:716, PMID 18413464 (urate analysis in 804 PRECEPT participants; trial dates April 2002 to August 2005)
• Not yet verified: the MPTP-mouse protection data (the paper's abstract says only "a variety of nonclinical models"); a 2017 conference report of late imaging changes, dropped from the text because it could not be sourced; why Cephalon stopped development.