Corestem Shares Protocol for Long-term NeuroNata-R Trial
Corestem is still enrolling participants in its Phase 3 clinical trial of NeuroNata-R (lenzumestrocel), a stem cell therapy that is conditionally approved to treat amyotrophic lateral sclerosis (ALS) in South Korea.
The trial, ALSummit (NCT04745299), is evaluating the safety of repeat NeuroNata-R injections and how well it works to prevent ALS progression and death for up to three years.
Recruitment started last year and is ongoing at five academic hospitals in South Korea. A total of 115 adult patients, ages 25–75, with an intermediate rate of progression are expected to enroll; information about contacts and locations is available.
ALSummit has been approved by the U.S. Food and Drug Administration (FDA) and South Korea Ministry of Food and Drug Safety. Its data is expected to support applications requesting a full approval in South Korea and a potential approval in the U.S.
The trial’s protocol was shared in the study, “Efficacy and safety of lenzumestrocel (NeuroNata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSummit study): Study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial,” which was published in the journal Trials.
Patients with ALS experience muscle wasting as they progressively lose their motor neurons — the nerve cells that carry information from the brain to the spinal cord and muscles. This causes progressive difficulties with how they move, eat, swallow, breathe, and talk.
NeuroNata-R uses mesenchymal stem cells (MSCs), which are adult stem cells that can renew themselves by dividing and are capable of maturing into many other types of cells. They also are believed to produce a number of molecules that modulate inflammation and improve nerve cell survival and function.
These cells are obtained from a patient’s bone marrow — the spongy tissue found inside the bones. Then they are grown in the lab and returned to the patient, mixed with their cerebrospinal fluid (CSF), via an intrathecal (into the spinal canal) injection. CSF is the substance that flows in and around the brain and the spinal cord.
In a previous Phase 1/2 clinical trial (NCT01363401), two repeated intrathecal injections given at an interval of 26 days slowed the progression of ALS for at least six months, compared with a control group that received no injection. This was assessed using the Revised ALS Functional Rating Scale (ALSFRS-R) scale, a tool that measures 12 aspects of physical function, from swallowing and using utensils, to climbing stairs and breathing.
ALSummit now was designed to evaluate the long-term safety and efficacy of NeuroNata-R in up to 115 adults with ALS, diagnosed with the familial or sporadic forms of the disease less than two years before enrollment. Participants must have an ALSFRS-R score in the range of 31 to 46 at the time of screening, and have experienced an increase of about one point per month in the 17 weeks prior to the first injection.
“Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity,” the researchers wrote.
Patients in the trial will be assigned randomly to one of three groups. One will receive two repeated intrathecal injections of NeuroNata-R at an interval of 26 days, plus three injections with a saline solution (that will serve as a placebo) given three months apart.
A second group will receive the two injections at an interval of 26 days, plus three additional booster injections at four, seven, and 10 months. A third, control group will receive the same five injections with saline only.
Notably, due to ethical concerns, patients in the control group will receive two injections of the active treatment at 13 and 14 months. Those in the other two groups will receive saline injections at the same timepoints.
The trial’s primary goal is a combined assessment of function and survival (CAFS), which is based on ALSFRS-R scores and survival, at six months for the first group and at 12 months for the second group, compared the control.
Other measures include a CAFS assessment at six months for the second group, as well as changes in lung function and muscle strength, and time to death. Side effects will be monitored throughout the entire clinical trial.
Participants who wish to roll over into a long-term follow-up study will be evaluated further for up to 36 months (three years).
While ALSummit is approved by the FDA, there are no plans to open additional sites there or elsewhere outside South Korea.