Doxycycline versus placebo in CJD (Italy and France, 121 patients)

Key facts

• Status: Completed; no benefit.
• Design: phase 2 randomised double-blind placebo-controlled trial in France and Italy; 663 patients were referred, 121 were randomised and 62 received doxycycline 100 mg a day.
• The trial stopped at 4.5 years after a prespecified interim analysis showed futility, with 86 of 97 evaluable patients already dead.
• Neither the intention-to-treat nor the per-protocol analysis showed a survival benefit; doxycycline was well tolerated and autopsy levels in 11 patients showed it reaches the brain.
• The result contradicted two earlier observational reports of benefit; the commentary warns that observational or historical series should not be relied on and that nearly half of 663 screened patients may not have had CJD.
• Stated weaknesses: weak preclinical efficacy for doxycycline, many enrolled patients with very advanced disease, and strain-dependence of drug response; strengths: it proved a multinational placebo-controlled design is feasible in a rare fast disease.
• An independent review lists it as 121 randomised patients in France and Italy and notes only symptomatic patients, mostly sporadic CJD, were studied across all completed drug trials.

Timeline

1. 2014Trial published online in Lancet Neurology.
2. 2015Independent review lists it among completed trials.