On 6 October, the company TauRx Therapeutics Ltd announced results from its LUCIDITY Phase III trial for the treatment of Alzheimer’s disease (AD). The LUCIDITY trial is a randomised, double-blind and placebo-controlled study evaluating the safety and efficacy of hydromethylthionine mesylate (HMTM) in people with AD ranging from Mild Cognitive Impairment (MCI) through to the moderate stage of disease. HMTM is taken orally and aims to inhibit the aggregation of tau (one of the proteins linked to Alzheimer’s pathology). The study enrolled 598 people with AD who were randomly assigned to receive HMTM or placebo. HMTM can cause variable urinary discolouration. Therefore, to maintain blinding, the placebo group received tablets containing a urinary discolourant, named methylthioninium chloride (MTC), given at a dose of 4 mg twice weekly, the minimum required to prevent bias arising from potential urinary discolouration. TauRx has now completed the first 12-month double-blind phase of the trial. The second 12-month open label period is ongoing, during which all participants receive HMTM. All participants were required to have a positive amyloid-PET scan. Results showed that participants who received MTC had unexpected blood levels of active drug above the threshold needed to produce a clinical effect.
The company reported that “in the absence of a true placebo, the trial as designed could not determine outcomes on primary clinical endpoints relative to a therapeutically inactive placebo as prespecified.” Based on this rationale, the company analysed and compared the study data with historical controls available from closely matched data from the Alzheimer’s Neuroimaging Initiative (ADNI). TauRx also compared individual outcomes at 6, 12 and 18 months to the same measures prior to initiating treatment. The company indicated that there was minimal decline over the first 12 months in participants receiving HMTM on both coprimary cognitive and functional endpoints (ADAS-cog11 and ADCS-ADL23). In the 105 participants with MCI, HMTM treatment resulted in a statistically significant cognitive improvement of 2 units over the pre-treatment baseline at 6, 12 and 18 months on the ADAS-cog13 scale. In the 147 participants with mild to moderate AD receiving HMTM, the company reported a stabilisation of cognition and function with a 2.5 unit cognitive decline in the first 9 months and no further decline over the following 9 months. According to TauRx, statistically significant reductions in disease progression as measured by change in cognitive function and brain atrophy were confirmed by comparisons of participants receiving HMTM with ADNI participants who were closest to the study population by age and clinical severity.
The company added that HMTM treatment resulted in a normalisation of brain atrophy in participants with MCI to a rate similar to healthy ADNI participants. For safety, the company indicated that HMTM is an oral drug with a strong safety profile. Findings showed that there were no serious treatment-related adverse events or evidence of amyloid related imaging abnormalities (ARIA), which can indicate the presence of brain micro-bleeds or swelling. The company will present the LUCIDITY findings at the upcoming Clinical Trials in Alzheimer’s Disease (CTAD) conference on 30 November (San Francisco, US).