Patients sought for Phase 2 trial of SAGE-718 for cognitive problems

Clinical trial enrollment for Parkinson's underway at 16 US sites

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Enrollment is still underway in a Phase 2 clinical trial testing Sage Therapeutics’ oral therapy SAGE-718 in people with mild cognitive impairment (MCI) due to Parkinson’s disease.

The trial is recruiting Parkinson’s patients at 16 sites across the U.S.

Dubbed PRECEDENT (NCT05318937), it’s designed to investigate SAGE-718’s effects against a placebo in adults with confirmed MCI due to Parkinson’s and mild to moderate motor impairment. Up to 76 participants, ages 50-75, will be enrolled in the 42-day trial.

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Clinical trial enrollment in SAGE-718 still ongoing

The Phase 2 PARADIGM trial (NCT04476017), now completed, found that SAGE-718 was safe and could improve cognitive function in people with Parkinson’s. That trial enrolled a similar patient group, but no placebo was involved; all participants received the experimental therapy.

Progress made in the SAGE-718 clinical program during 2022, along with updates on other therapies in the company’s pipeline, was summarized by Sage in a press release and new investor report.

“We have been laser focused on the opportunity to help millions of people who are desperate for new treatment options,” Barry Greene, Sage’s CEO of Sage, said in the release, noting that the company has been “progressing a promising and targeted pipeline.”

“This momentum puts us in a position of strength as we kick off 2023 and progress in our plan to become the leader in brain health and a top tier biopharmaceutical company,” Greene added.

Parkinson’s is a progressive neurodegenerative disease and nerve cells that produce dopamine, an important brain signaling chemical, are increasingly lost over its course. One of dopamine’s roles is to regulate activity at N-methyl-D-aspartate (NMDA) receptors — proteins in the brain that are essential for proper nerve cell communication.

It’s thought that damage to dopamine-producing cells in Parkinson’s may drive cognitive impairments via disruption of NMDA signaling.

SAGE-718 works to modulate NMDA receptor activity in an effort to restore nerve cell communication. In turn, the treatment is expected to help improve cognitive function in people with neurological diseases marked by cognitive impairment, including Parkinson’s.

We have been laser focused on the opportunity to help millions of people who are desperate for new treatment options.

The two-part Phase 2 PARADIGM trial enrolled 18 adults, ages 50-75, with Parkinson’s and MCI.

In part A, 11 patients were treated for two weeks with SAGE-718, given as a 3 mg tablet once daily in the morning with food. In part B, participants were treated similarly, but for four weeks.

Results from part A showed that two weeks of treatment led to improvements in a range of measures of executive function, a set of cognitive skills involved in everyday life that include planning, decision making, working memory, multitasking, and cognitive flexibility.

Data also indicated that the treatment may be able to boost learning and memory, as assessed by tests evaluating pattern recognition and verbal memory.

Gains were sustained for at least two weeks after treatment completion. The treatment also was well tolerated, with no therapy-related side effects and no serious side effects reported.

Findings from part B were similar, according to Sage, with gains in executive function sustained through the four weeks of treatment.

The ongoing Phase 2 PRECEDENT trial, also called CNP-202, aims to establish the safety and efficacy of SAGE-718 in Parkinson’s patients with MCI. Participants are randomly assigned to receive SAGE-718 softgel capsules (1.2 mg) or a placebo once daily in the morning for 42 days, or about six weeks.

The main goal is to assess changes in performance on the Wechsler Adult Intelligence Scale-IV (WAIS-IV), a standard test of cognitive function. Key secondary endpoints include safety and tolerability.

The trial is expected to be completed by September.

A number of trials are ongoing to evaluate SAGE-718 for other neurodegenerative conditions marked by cognitive impairment, including Huntington’s and Alzheimer’s diseases.

Sage, in collaboration with Biogen, also is developing an investigational therapy for movement and neurological disorders — including essential tremor and Parkinson’s. That therapy candidate, called SAGE-324, has been shown to improve tremor control and the ability to perform daily life activities among people with essential tremors, but has not been evaluated in Parkinson’s patients.