BrainStorm's Phase 3 NurOwn Trial

Who can be in the trial?

Inclusion in the Phase 3 trial is limited to men and women ages 18-60 that have been diagnosed with ALS (based on a standardized set of criteria) and had ALS symptoms for less than 2 years at the time of their first trial screening visit, among other requirements. Continued use of riluzole is permitted, but patients using certain other approved, experimental, or non-approved treatments have to discontinue their use before starting the trial. Frustratingly for some, this exclusion includes the use of Radicava which was approved a few weeks before the trial started enrolling. Additionally, patients who have previously received a stem cell treatment, including NurOwn® in Phase 1 or 2, are excluded as the long-term impact of that factor is unknown.


The trial design includes several additional factors to ensure that the final results will be reliable and the effect of NurOwn®, either beneficial or not, will be conclusive.

Study Population

The study is enrolling 200 patients, which is relatively large for a treatment that requires multiple invasive procedures. Of this total, half will receive the NurOwn® treatment and half will receive a non-functional placebo treatment. More than 200 patients will be screened, but those who are determined to be slow progressors or don't meet other inclusion criteria will have to exit the trial after the 3-month screening period.

Placebo-Controlled

The  “placebo effect,” where persons receiving a non-functional treatment often report positive results due to their own belief that they are getting an actual treatment, needs to be controlled in a well-designed clinical trial. In this Phase 3 trial, patients who receive a placebo treatment will still undergo all of the same procedures as NurOwn®-treated patients, including bone marrow aspirations, intrathecal injections, and lumbar punctures to sample the cerebral-spinal fluid. This ensures that if positive results are seen in the NurOwn®-treated group (as compared to the placebo-treated group) then the benefit would most likely be the result of the treatment, not any other reason.   

Read a great national geographic article on how powerful the placebo effect is

Randomized

The selection of patients receiving treatment vs. those receiving the placebo is done randomly by a computer program administered by a third party. This randomization ensures that no person involved in the trial selects patients for the NurOwn® treatment that they think will benefit the most-a bias that would make the trial results less reliable.

Double-Blind

Neither the doctors and clinical staff nor the patients themselves are informed as to which patients are receiving the NurOwn® treatment for the entire duration of the trial. A separate “unblinded” staff uninvolved with the trial does the actual intrathecal injections, as they might recognize a difference between the NurOwn® and placebo treatment fluids. Important to note is that patients in the trial are not "unblinded" until the entire trial is complete, not just their own trial period. Currently BrainStorm is projecting a mid-2020 completion date. Also important is that until that trial completion date, those who have completed their own trial involvement will likely be ineligible for other clinical trials. This should be understood and accepted by every potential patient before enrolling in this trial. 

Repeat Dosing

Previous NurOwn trials included only a single NurOwn® treatment or placebo. This Phase 3 trial includes three treatments (at 8-week intervals) over a longer total trial duration of about 11-1/2 months, including pre- and post-treatment monitoring. If NurOwn® is effective as a treatment, more doses and a longer trial duration should more clearly show a benefit from NurOwn® as compared to a placebo treatment.

Clinical Trial Visit Schedule

The trial requires a total of 14 visits over 11 months. At MGH, the first four visits include an initial screening visit to ensure the candidate meets the inclusion criteria and to start tracking his or her ALSFRS-R score. Candidates who do not show a sufficient decline in scores over the course of these visits are eliminated from the trial at the end of visit 4, as it is difficult to show an improvement or slowing of disease progression during the course of a trial in patients whose progression is very slow. 


The bone marrow aspiration occurs during visit 5, and the initial intrathecal injection of NurOwn® or the placebo fluid occurs about 5 weeks later at visit 6, with repeated doses at visits 9 and 11. The injection requires only local anesthesia but an overnight hospital stay is necessary to observe the patient for any negative reactions. Of the 14 total visits, the balance are strictly monitoring visits at which the trial coordinators collect a variety of patient data points including, among others, ALSFRS-R scores, blood and cerebrospinal fluid samples, and breathing capacity test values. The hope of this Phase 3 trial is that BrainStorm can eventually use the collected data to prove the safety and effectiveness of NurOwn® in its application for FDA approval as a treatment for ALS.