Probiodrug AG, a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer’s disease (AD), announced that the study design of the ongoing phase IIa SAPHIR trial comparing PQ912 to placebo presented as a poster on Thursday, December 8, 2016 at the 9th Clinical Trials on Alzheimer’s disease (CTAD) meeting in San Diego, USA.

 The SAPHIR study is a 3 month study in treatment naïve patients with early AD. PQ912 targets the inhibition of the Glutaminylcyclase (QC) resulting in a reduction of the production of neurotoxic pyroGlu-Abeta (pGlu-Abeta) and related oligomers. PQ912 has been extensively investigated in phase 1 Multiple ascending dose studies (MAD) showing good tolerability and a dose dependent QC-inhibition in the spinal fluid.

The SAPHIR study has been designed and is conducted in collaboration with Philip Scheltens, M.D., Ph.D., the VUmc Amsterdam (NL) and the CRO Julius Clinical (NL).

The primary objective of the SAPHIR study is to investigate the safety of PQ912 in the target population and the secondary objective is to assess the pharmacodynamic profile. The publication at CTAD reveals that the study applies a series of methodological innovations which in this combination has not been executed before in an early AD study. Specific in and exclusion criteria based on diagnostic biomarkers of Abeta and tau were required to be met by all patients to ensure a high confidence of the diagnosis of early AD. Mini–Mental State Examination (MMSE) and Cogstate test battery assessments at baseline are monitored blindly every 30 patients to ensure consistency and reliability of ratings. A number of exploratory endpoints like EEG, fMRI and a series of CSF based biomarkers including QC-activity, pGlu-Abeta, Abeta oligomers, neurogranin as well as inflammation markers are centrally analysed. Based on an exploratory analysis of 86 randomised patients, a low standard deviation for the Neuro-psychological test battery and functional EEG at baseline has been observed.

Prof Philip Scheltens, director of the Alzheimer Center at the VUmc in Amsterdam and Chairman of the SAPHIR study, said: “The combination of in and exclusion criteria together with the primary and innovative exploratory outcome parameter in the SAPHIR study is unique for an early AD study. We are excited to see the full results in the second quarter of 2017.”