Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model

Advancing Parkinson’s disease research through early-phase clinical trials

Synucleinopathies such as Parkinsońs disease (PD), Dementia with Lewy odies (DLB) and Multiple System Atrophy (MSA) are characterized by deposition of misfolded and aggregated a-synuclein. Small aggregates (oligomers) of a-synuclein have been shown to be the most relevant neurotoxic species and are targeted by anle138b, an orally bioavailable small molecule compound which shows strong disease-modifying effects in animal models of synucleinopathies.

A randomised, double-blind, placebo-controlled phase 1a trial

Anle138b was studied in a single-centre, double-blind, randomised, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy subjects. Between December 2019 and June 2020, Quotient Sciences screened 196 healthy volunteers were screened and 68 participants were enrolled as part of this trial, all completing the study per protocol and with no major protocol deviations. 

Healthy volunteers supporting Parkinson’s disease research

Eligible participants were randomly assigned (1:1 for sentinel subjects and 1:5 for main group) to placebo or anle138b (dose range 50 mg to 300 mg per day), respectively. In addition, the effect of food on the pharmakokinetics of anle138b in healthy subjects was examined in doses of 150 mg per day.

Adverse events were mostly mild and all fully recovered or resolved prior to discharge. From baseline to completion of the trial no medically significant individual changes were observed in any system organ class. Already at multiple doses of 200 mg, exposure levels above the fully effective exposure in the MI2 mouse Parkinson model were observed.

The research demonstrates how a carefully designed Phase 1 study in healthy volunteers was used to assesscritical milestones before advancing into patient studies. The findings supported continued clinical development towards new therapies to address Parkinson’s disease.

Continue reading the outcomes of this study conducted at Quotient Sciences, funded by MODAG GmbH (later acquired by Teva) and with a grant from the Michael J. Fox foundation for Parkinson’s Research.