First MS Patient Dosed in Phase 2 Trial of Potential Remyelinating Therapy CNM-Au8, Clene Announces

The first participant has been dosed in the Phase 2 REPAIR-MS clinical trial examining the effects of CNM-Au8, Clene Nanomedicine‘s investigational remyelinating therapy, on brain metabolism in people with multiple sclerosis (MS), the company announced.

In MS, the immune system attacks myelin, the protective sheath that surrounds neurons, helping them send signals more effectively.

Most approved MS therapies can prevent further myelin damage by reducing the activity of the immune system. However, none of these therapies are able to replace the myelin that has already been lost. For this reason, MS research has been focusing on developing a so-called remyelinating therapy.

CNM-Au8 is a solution of gold nanoparticles with a particular crystal structure that can help facilitate certain chemical reactions within cells. It can also promote the activation of oligodendrocytes, the cells responsible for producing myelin.

Preclinical data in animal models of MS suggested that CNM-Au8 is able to induce remyelination, and preliminary clinical studies in healthy volunteers indicated the medication has a good safety profile.

REPAIR-MS (NCT03993171) is an open-label Phase 2 trial sponsored by Clene to assess the safety, pharmacokinetic and pharmacodynamic properties, and metabolic effects of CNM-Au8 in 24 adults with relapsing MS (which includes relapsing-remitting and secondary progressive disease) diagnosed within the past 15 years.

Pharmacokinetics and pharmacodynamics refer to the interactions between the body and a specific compound. These interactions are analyzed to understand how a medication is absorbed, distributed, metabolized, and then eliminated from the body.

Participants enrolled in the study will drink approximately 2 oz. (60 mL) of CNM-Au8 every morning for 12 weeks.

The study is being conducted at the University of Texas Southwestern. More details can be found here.

“The objective of the open-label, investigator-blinded REPAIR-MS study is to demonstrate improvements in brain bioenergetic metabolism in multiple sclerosis patients treated with CNM-Au8,” Robert Glanzman, MD, chief medical officer of Clene, said in a press release.

Investigators will tackle this goal by analyzing changes in the NAD+ and NADH ratio, which controls several cellular processes, including the production of adenosine triphosphate, a small molecule used as “fuel” by all cells in the body.

These changes — and other alterations in the metabolic makeup of the brain — will be assessed using ³¹phosphorous magnetic resonance spectroscopy, an imaging technique that allows scientists to measure the levels of molecules such as NAD+/NADH in individuals.

The results could “show how treatment with CNM-Au8 results in bioenergetic improvement of impaired neuronal redox state,” Glanzman said.

Another Phase 2 trial, called VISIONARY-MS (NCT03536559), currently underway in Australia, is also investigating the efficacy and safety of CNM-Au8 in adults with relapsing MS.

This trial, which recently received a large grant from the National Multiple Sclerosis Society, is directly testing the remyelinating potential of CNM-Au8 in approximately 150 patients who have partial vision loss due to lesions caused by the disease.

“We are excited to advance CNM-Au8 clinically into our second Phase 2 study for MS patients,” said Rob Etherington, president and CEO of Clene.

“Our preclinical data with CNM-Au8 demonstrated improvements in cellular bioenergetics, specifically within neurons and oligodendrocytes, which led to the initiation of the VISIONARY-MS Phase 2 study and now the REPAIR-MS Phase 2 trial. Currently, there are no therapies approved for remyelination, and we believe CNM-Au8 has the strong potential for myelin repair and protection of neurons in patients with MS,” he concluded.