Study protocol of RESCUE-ALS: A Phase 2, randomised, double-blind, placebo-controlled study in early symptomatic amyotrophic lateral sclerosis patients to assess bioenergetic catalysis with CNM-Au8 as a mechanism to slow disease progression

Abstract

IntroductionAmyotrophic lateral sclerosis (ALS) is an adult-onset, progressive and universally fatal neurodegenerative disorder. In Europe, Australia and Canada, riluzole is the only approved therapeutic agent for the treatment of ALS, while in the USA, riluzole and edaravone have been approved by the Food and Drug Administration (FDA) . Neither riluzole nor edaravone treatment has resulted in substantial disease-modifying effects. There is, therefore, an urgent need for drugs that result in safe and effective treatment. Here, we present the design and rationale for the phase 2 RESCUE-ALS study, investigating the novel nanocatalytic drug, CNM-Au8, as a therapeutic intervention that enhances the metabolic and energetic capacity of motor neurones. CNM-Au8 is an aqueous suspension of clean-surfaced, faceted gold nanocrystals that have extraordinary catalytic capabilities, that enhance efficiencies of key metabolic reactions, while simultaneously reducing levels of reactive oxygen species. This trial utilises a novel design by employing motor unit number index (MUNIX), measured by electromyography, as a quantitative measure of lower motor neurone loss and as an early marker of ALS disease progression.Methods and analysisThis is a multicentre, randomised, double-blind, parallel group, placebo-controlled study of the efficacy, safety, pharmacokinetics and pharmacodynamics of CNM-Au8 in ALS patients. Patients will be randomised 1:1 to either receive 30 mg of CNM-Au8 once daily or matching placebo over a 36-week double-blind treatment period. Efficacy will be assessed as the change in motor neurone loss as measured by electromyography (eg, MUNIX, the primary endpoint; and secondary endpoints including MScanFit, motor unit size index, Split Hand Index, Neurophysiology Index). Exploratory endpoints include standard clinical and quality of life assessments.Ethics and disseminationRESCUE-ALS was approved by the Western Sydney Local Health District Human Research Ethics Committee (Ethics Ref: 2019/ETH12107). Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT04098406

Clinical translation of gold nanoparticles

“…A few months later, a phase II (NCT04098406) and a multicenter phase II/III (NCT04414345) clinical trials were initiated where ALS patients were treated daily with 30 mg (or 60 mg) of CNM-Au8 for 36 and 24 weeks, respectively. The phase II clinical trial [ 47 ] was completed in 2021, and Clene Nanomoedicine announced that despite not meeting the primary and secondary biomarker endpoints (associated with preventing motor neuron loss and lung function decline), the treatment significantly slowed the disease progression and there was evidence of long-term survival benefit. This study was followed up by an optional 48-week open-label trial extension to the participants that had completed the previous study (NCT05299658).…”

A Historical Review of Brain Drug Delivery

“…CNM-Au8 is a preparation of gold nanocrystals which are daily administered orally at a dose of 30 mg, and were tested in a phase 2 trial for ALS [932]. The trial was completed in 2022 and no results were yet reported (NCT04098406).…”

The Applications of Gold Nanoparticles in the Diagnosis and Treatment of Gastrointestinal Cancer

“…Fifty years later, Hirsh et al found that GNPs irradiated with an electromagnetic wavelength at 820 nm were able to increase the surrounding temperature, which could be used for the treatment of solid tumor (18). In July 2019, the U.S. Food and Drug Administration (FDA) approved an oral drug based on GNPs (CNM-Au8, Clene Nanomedicine, Inc.) for the treatment of amyotrophic lateral sclerosis (ALS) (19). This demonstrated that GNPs are a safe and reliable tool with great potential for disease treatment.…”