Dosing Begins in Phase 2 Study of Nanomedicine as Disease-modifying ALS Treatment

A first patient has been dosed in a Phase 2 trial testing a nanomedicine called CNM-Au8 as a potentially disease-modifying therapy for people with amyotrophic lateral sclerosis (ALS).

This safety and efficacy study, due to finish in April 2021, is also completely enrolled, Clene Nanomedicine, the treatment’s developer, announced in a press release.

“We are excited to advance CNM-Au8 clinically into this Phase 2 study for ALS patients,” Rob Etherington, president and chief executive officer of Clene, said in the release. “As neurodegenerative diseases such as ALS have very few treatment options, this study will prove whether CNM-Au8 may be … effective.”

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.

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 (NCT02755870).

The randomized, double-blind and placebo-controlled Phase 2 study, called RESCUE-ALS (NCT04098406), 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 are being 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 complete this treatment period may move into a separate and open-label study, where all will receive CNM-Au8.

“The objective of the … RESCUE-ALS study is to demonstrate that improvements in brain bioenergetic cellular support in early symptomatic ALS patients treated with CNM-Au8 will help preserve motor neurons survival and function,” said Robert Glanzman, MD, FAAN, Clene’s chief medical officer.

Changes in the health of motor nerve cells — the study’s main goal or primary endpoint — will be assessed through differences between treatment and placebo patient groups seen in Motor Unit Number Index (MUNIX) scores. This test, given at the study’s start and again after treatment ends (week 36), is an established way of measuring motor neuron loss in ALS, the disease’s “primary cause of clinical progression,” Glanzman said.

Treatment efficacy will also be measured through changes in ALS Functional Rating Scale revised (ALSFRS-R) scores, among other assessments.

“We are very excited to partner with Clene on the Phase 2 study in ALS,” said Steve Vucic, director of neurophysiology at Sydney Medical School, Westmead Hospital. “CNM-Au8 offers an innovative approach of potentially treating neurodegenerative diseases, such as ALS, for which there are no effective treatments at present.

“We are hopeful that CNM-Au8 will be an effective therapy … and this trial will go a long way in addressing this question.”

RESCUE-ALS is partly funded by FightMND, a nonprofit patient advocate group in Australia working to raise awareness of motor neuron disease (MND) in that country.

CNM-Au8 is also being evaluated in Phase 2 trials in people with multiple sclerosis (NCT03536559) and (NCT03993171), and  with Parkinson’s disease (NCT03815916).