NervGen is conducting a Phase 1a/2b clinical trial of NVG-291, which is better than a phase lll trial and could get the FDA to approve NVG-291 in short order.
Previously there were:
Phase I studies which were done to find the highest dose of a new treatment that can be given safely without causing severe side effects.
If a new treatment was found to be safe in phase I clinical trials, a phase II clinical trial was done to see if the medication is helpful in controlling the disease that the medication is targeting.
- Usually in a phase II clinical trial, everyone gets the same dose. But some phase II studies randomly assign people to different treatment groups. These groups may get different doses or get the treatment in different ways to see which provides the best balance of safety and response.
- Placebos (inert tablets [like sugar pills], inert injections [like saline]) are not used in phase II trials.
Phase III clinical trials: Is it better than what’s already available?
Placebos may be used in phase III studies.
In order to show that a proposed medication is effective, a company has to run a phase 3 clinical trial. But that involves hundreds, or even thousands of subjects. That is VERY EXPENSIVE. Now the FDA allows 1a/2b trials which involve only a few dozen subjects. This will indicate the medication's safety, (1a) and the 2b will indicate its effectiveness. NervGen's trial will include placebo patients. Because the patients won't know if they are getting the company's medication, or a placebo, and the clinicians conducting the trial won't know which subjects are actually receiving the company's medication, this is called a double-blind study. A double-blind study is considered to be the gold standard of clinical studies.
If the medication being tested is for an urgent unmet medical need and if the results are from a double-blind clinical study, and the results are outstanding and show a strong positive response, the FDA may grant immediate approval of the medication, with the stipulation that the company has to monitor the medication's effectiveness and any side effects. If serious side effects show up, the FDA may withdraw its approval and require the company to conduct a phase 3 clinical trial.
NervGen is recruiting 40 subjects for its spinal cord injury study. Half of the subjects will receive its NVG-291 medication, and the other half will receive a placebo.
The subjects will consist of two groups.
(Chronic cohort 1) will be people who have had a cervical (neck) spinal cord injury (SCI) for 1 to 10 years.
(Subacute cohort 2) will have suffered a spinal cord injury within the last 10 to 49 days.
Recruitment of spinal injury subjects started 8 August 2023, but it wasn't until the 25 of September that the first subject (person) to meet the strict criteria of the study was admitted to the clinical trial.
Criteria
Cervical SCI (spinal cord injury) resulting from acute physical trauma.
Must be able to volitionally initiate at least one step on one leg (may be without body weight support).
Must have a Walking Index for Spinal Cord Injury II (WISCI II) score as follows:
- For Chronic cohort 1: Less than or equal to Level 14.
- For Subacute cohort 2: Less than or equal to Level 8.
GRASSP Prehension Ability score
For Chronic cohort 1:
i) Must have a score of at least 2 on at least one of the Prehension Ability grasp patterns of the GRASSP assessment in at least one upper extremity.
ii. Must have no more than one Prehension Ability grasp patterns score = 4 in the upper extremity satisfying criterion i.
For Subacute cohort 2:
i) Must have a score of 2 on at least one of the Prehension Ability grasp patterns of the GRASSP assessment in at least one upper extremity.
ii. Must have no more than one Prehension Ability grasp patterns score = 3 in the upper extremity satisfying criterion i.
Both groups must have:
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Graded and Redefined Assessment of Strength, Sensibility, and Prehension Test
Hand function Max Score 116 points (higher is better)
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Lower extremity motor score
Lower extremity Max Score 50 points (25 points per side - higher is better)
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Upper extremity motor score
Upper extremity Max Score 50 points (25 points per side - higher is better)
Exclusion Criteria:
Nontraumatic SCI (e.g., due to infection, ischemia, metabolic abnormality, congenital abnormality, malignancy, radiation injury, or other disease process).
Spinal cord injury due to gunshot wound or penetrating injury.
Two or more (noncontiguous) spinal cord lesions.
Each candidate will receive a four-month trial (of the medication, or placebo).
The results will be tabulated along with all the other recruited subject's 4-month results.
Even after the four months is finished, they will continue to be monitored.
Enrolment is still open because 40 subjects have not yet been enrolled.
The study will end on August 30, 2024, even if 40 people have not been enrolled by that time. If 40 subjects have been recruited before that date, the clinical trial will end four months after the last subject has finished their 4-month trial period. The results of the clinical trial will then be announced.
The 4-month trial for the first enrolled patients in September 2023 will be up by the end of this January. Their results will be official, and the company could announce how well they reacted, although they wouldn't know which ones had received the company's medicine or a placebo. But the results will speak for themselves. Spinal cord injury patient's that have reached a plateau do not recover use of a paralyzed limb. If this is happening, the FDA will consider it to be a groundbreaking event.
Because spinal cord injury patients are not expected to show overt improvements, such as movement of paralyzed limbs or hands/feet, the primary endpoint for proof that NervGen's medication has reversed at least some of the damage to the spinal cord neurons, will be an electrical conduction test of the neurons ability to pass signals from the brain to the muscles that they are intended to activate.
Thus, the primary objective is to assess the change in corticospinal connectivity of defined upper and lower extremity muscle groups following treatment based on changes in motor evoked potential amplitudes. Secondary objectives are to evaluate changes in the motor function of upper and lower limbs and extremity dexterity and grasping and mobility. Each cohort will be evaluated independently as the data becomes available.
Secondary endpoints are normally considered to be minor goals, but actual movement in previously paralyzed limbs, which is the secondary goal in our case, would actually be a major result. In spinal cord injuries, according to data from the European Multicenter Study of Human Spinal Cord Injury, ninety percent neurological recovery as measured by LEMS and functional improvement occurs within the first 3 months after trauma in all patients with traumatic spinal cord injury. A plateau is developed within 6 months. After 6 months, change in recovery is minimal.
Therefore, because half of the patients being tested have had their injury for 1 to 10 years, any return of motion after that time is listed as secondary because it is not expected to happen. If return of any motion is achieved this would be considered astounding. Any improvement in the other half of the patients whose injuries are recent, within the last 10 to 49 days, will be compared to the data base for such injuries to see if the improvement is better than expected.
Motor evoked potentials (MEPs) monitor the integrity of neurons from the brain or spinal cord to peripheral muscle groups by monitoring the amplitude of the signal that reaches the targeted muscle group. MEPs monitor the corticospinal tract beginning with a stimulus at the motor cortex, which travels along the corticospinal tract of the spinal cord to the nerve root, and then the peripheral nerve which terminates in the muscle group that is being monitored.
An improvement in a person's motor evoked potential would mean that there has been an improvement in the integrity of their damaged neurons. This has previously never been achieved.
MEPs and their amplitude of stroke patients or patients with newly injured spinal cords are useful predictors of upper and/or lower limb motor function recovery after stroke or spinal cord injury. Previous examination of stroke and spinal cord injury patient's MEPs and their amplitude significantly correlated with improvement of upper-limb paresis and general outcome after 3 months, the period of time in which a patient regains most of their movement.
Transcranial electrical stimulation is applied through electrodes placed on the scalp, while responses are recorded in the peripheral muscle group.
Any improvement of NervGen's clinical subject's MEP/amplitude score can be compared to the data base of the scores of stroke and SCI patients and their improvement potential. Any improvement above thjis data base will show the improvement that NervGen's drug has produced in their clinical group's subjects. Since they will continue to be monitored, if they do regain any movement, especially if they regain significant movement, this would be an astounding result and would make the FDA closely evaluate their results, possibly leading to an approval of their medication.