Phase 2 Remyelination Trial Yields ‘Intriguing’ Interim Results – Medscape

WEST PALM BEACH, FL Among patients with relapsing multiple sclerosis (MS) and visual impairment who received a potential remyelinating treatment or placebo for as long as 36 weeks, median low-contrast letter acuity improved in the population overall, according to an interim, blinded analysis.

Exploratory outcome measures of cognition, gait, and upper extremity function also improved.

The results do not mean that the treatment works. "We know that placebo works. I'm not here to tell you that the drug works. I'm just here to tell you that we have intriguing data," said Robert Glanzman, MD, chief medical officer of Clene Nanomedicine, the developer of the drug.

The patients in the interim analysis represent about 25% of the target study population of 150 patients, Glanzman said. The phase 2, double-blind, randomized, controlled trial, VISIONARY-MS, is assessing the efficacy and safety of CNM-Au8, a suspension of clean-surfaced gold nanocrystals that may support intracellular biologic processes. Patients are randomly assigned to receive low-dose CNM-Au8, high-dose CNM-Au8, or placebo taken orally once daily.

Neuroprotective or remyelinating agents are an unmet need in MS, Glanzman said. VISIONARY-MS has enrolled patients at centers in Australia and recently expanded the trial sites in North America. He presented the interim data during a joint symposium of the North American Imaging in MS Cooperative and the International Multiple Sclerosis Visual System Consortium at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

VISIONARY-MS is enrolling participants with chronic optic neuropathy, defined as visual impairment with no episodes of acute optic neuritis within the 6 months prior to enrollment, and nonactive disease, defined as no MS relapses within the prior 3 months. Patients may take concomitant immunomodulatory disease-modifying MS therapies during the trial.

The primary endpoint is improvement in low-contrast letter acuity (LCLA) from baseline to week 24. Secondary endpoints are change in amplitude and latency of multifocal visual evoked potential. Other functional measures are exploratory endpoints. Participants remain in the trial through week 48 or until the last participant completes week 24.

Among the first 34 enrolled participants, median LCLA improved by about five letters, Glanzman said.

Patients also had median improvement on other subscales of the modified Multiple Sclerosis Functional Composite (MSFC) that assess cognition (Symbol Digit Modalities Test), upper extremity function (9-Hole Peg Test), and gait (Timed 25-foot Walk).

CNM-Au8 has been well tolerated, and no serious adverse events related to the study drug have been reported. The most frequent adverse events include headache, upper respiratory infection, and sore throat. Full unblinded results are anticipated in 2021.

About 60% of patients in the interim analysis were female, and the mean Expanded Disability Status Scale score was less than 2, Glanzman said.

"These data add to the growing body of clinical evidence demonstrating that CNM-Au8, a suspension of catalytic, clean-surfaced, faceted gold nanocrystals, has the unique ability to improve remyelination and provide axonal neuroprotection," Glanzman said in a news release. "The consistent median improvements observed across the MSFC functional domains in the population of participants in VISIONARY-MS are exciting."

At previous meetings, research has described data from studies that have provided evidence of efficacy in animal models of MS. An overview of the preclinical studies "Nanocatalytic activity of clean-surfaced, faceted nanocrystalline gold enhances remyelination in animal models of multiple sclerosis" was published recently in Scientific Reports. Preclinical studies in animal models of diseases other than MS also have shown evidence of neuroprotection, Glanzman said.

"We are studying the visual system in order to interrogate the nervous system as a whole," he said. "The visual system is by far the most sensitive to change." The design of VISIONARY-MS was informed by a trial of clemastine fumarate as a potential remyelinating agent in patients with chronic optic neuropathy, Glanzman added.

Glanzman is an employee of Clene Nanomedicine, and receives salary and stock options.

Source: 5th annual Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2020. Abstract.

This story originally appeared on MDedge.com.

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Phase 2 Remyelination Trial Yields 'Intriguing' Interim Results - Medscape