MND Australia


Phase 2

What is the RESCUE-ALS Study?

This was a multi-centre randomised, double-blind, parallel group, placebo-controlled Phase 2 study of the efficacy, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8. 

CNM-Au8 is an oral, gold nanocrystal liquid suspension designed to assist cells with the energy they need to function well. It works by supporting bioenergetic cellular reactions, and helping to remove the toxic byproducts of cellular metabolism that add to the breakdown of motor neurons in ALS.

The drug has been developed by Clene Nanomedicine.

Preclinical studies have shown the nanomedicine improves nerve cell survival and response to cellular stress, and lowers intracellular levels of toxic reactive oxygen species. CNM-Au8 was seen to improve motor function in rodent models ALS, multiple sclerosis, and Parkinson’s disease.

CNM-Au8 was also found to be safe in a Phase 1 trial of escalating doses in healthy volunteers.

What is involved?

The randomised, double-blind and placebo-controlled Phase 2 study, called RESCUE-ALS, enrolled up to 42 people, ages 40 to 80, with newly evident disease symptoms at two sites in Australia. Symptoms were considered newly evident if they began within 24 months of screening for this study, or 12 months of a probable or definite ALS diagnosis.

Participants were treated with CNM-Au8 or given a liquid placebo once each morning for 36 consecutive weeks (about eight months), in addition to standard care. Those who completed this treatment period could move into a separate and open-label study, where all will receive CNM-Au8.

The study was completed in November 2021. 

Summary of Phase 2 results

The trial did not meet its primary and a key secondary goal after 36 weeks of treatment: higher Motor Unit Number Index (MUNIX) scores — which measure the number, function, and health of motor neurons — and greater forced vital capacity (FVC), a measure of lung health.

However, a trend toward better MUNIX scores was evident at 12 weeks among patients taking CNM-Au8.

A significant effect in MUNIX at 12 weeks among patients with limb onset ALS, and a trend toward improvement at 36 weeks was also demonstrated. Limb onset occurs in about 70% of all ALS patients.

Exploratory measures also showed that CNM-Au8 significantly slowed disease progression, as assessed with the ALS Functional Rating Scale-Revised (ALSFRS-R), with a smaller proportion of treated patients with a six-point decline in that scale. In addition, quality of life at week 36 was significantly better in patients taking the investigational therapy, and there was evidence of benefit in long-term survival.

CNM-Au8 is also being evaluated alongside four other potential ALS therapies in the HEALEY ALS Platform Trial (NCT04297683), a multicentre and multiple therapy trial aiming to speed the development of promising treatments.

CNM-Au8’s HEALEY arm (NCT04414345), enrolling by invitation, reached 50% of its intended patient group in March 2021 and will include up to 160 adults with familial or sporadic ALS. Data is expected from HEALEY late 2022.

Rob Etherington, Clene’s CEO stated “We believe these RESCUE-ALS results show the potential of CNM-Au8 to bring meaningful benefit to people living with ALS. In the second half of next year, we expect to report results from the HEALEY ALS Platform Trial with the objective of confirming CNM-Au8 as an effective disease-modifying therapy for people with ALS.”.

How far off is a treatment?

A possible treatment resulting from this study is years away. This research will provide preliminary data on the safety and efficacy of CNM-Au8 as well as best dosing regimes.

Further information is available here