One of the most talked about topics in ALS research, among people with ALS, doctors and researchers alike, is the work being done exploring and developing potential stem cell treatments for ALS. For at least two decades, academic researchers and biotechnology companies have investigated several different stem cell therapies in people with ALS, including Brainstorm Cell Therapeutics’ NurOwn. NurOwn was first trialed in 2010 in Israel and has since been in two additional phase 2 clinical trials in Israel and the USA.
This recap addresses the upcoming phase 3 clinical trial that Brainstorm has announced through various public statements. However, an official posting on clinicaltrials.gov is not yet available, so some details regarding trial design are missing. In the meantime, so people with ALS have the latest information, we have gathered what we know about the trial’s enrollment criteria, locations, etc. online here. According to the company, sites will begin screening potential participants later this month.
Recent Phase 2 Trial Reads out Positive
Recently, an extensive review of ongoing stem cell trials was held by the ALS Therapy Development Institute, in which phase 2 clinical trial data from Brainstorm was discussed. The phase 2 trial included 48 people with ALS, enrolled across three sites. Each participant underwent a single procedure to harvest tissue from their spinal cord followed several weeks later by a single stem cell transplantation visit which included both intramuscular and intrathecal injections. A total of 36 individuals enrolled were randomized into the treatment group, with the remaining 12 receiving a placebo. The trial found treatment was safe and well tolerated within people with ALS.
Researchers involved in the study and analysts at Brainstorm conducted a post hoc analysis of data comparing “fast” versus “slow” progressors in both the treated and untreated group. Slow progressors were defined by the analysts as individuals with ALS whom lost two points or less on their ALSFRS-R between their screening and baseline visits, which occurred approximately three months apart.
While this was an important phase 2 study, it is important to note that neither the overall study, nor the post hoc analysis were powered to measure for efficacy using the ALSFRS-R score. This is not uncommon, as phase 2 studies are typically designed to provide additional safety and tolerability data only, while at the same time informing an investigator how to best design a larger pivotal phase 3 study to measure efficacy as its primary endpoint. The principal investigators reported promising efficacy data through their post hoc analysis, when excluding “slow progressors”, but stopped short of making claims that NurOwn was effective in treating a person’s ALS. Taken together, these and other data encouraged the investigators to execute the phase 3 study, described in detail below.
Six Sites Coast to Coast to Enroll 200
The planned phase 3 clinical trial will occur in the United States with a goal of enrolling 200 people with ALS. The 50% placebo controlled study (known as BCT-002-US) will include six enrollment sites; Massachusetts General Hospital, University of Massachusetts Medical Center, Mayo Clinic, California Pacific Medical Center and University of California-Irvine and an additional site not yet announced (although Duke University has been cited as the most likely sixth site).
Individuals with ALS interested in this study should consider that it will require 14 outpatient visits to the enrollment center during this important clinical trial. No financial assistance is being provided by BrainStorm to cover participants costs associated with travel to study sites. Due to the number of visits it is not surprising that investigators plan to focus on enrolling individuals that live within 100 miles of an enrollment site.
The first step in the enrollment process will be for individuals with ALS to secure a screening visit at an enrollment location. Singing up for the mailing list with BrainStorm Cell Therapeutics or here will help ensure people with ALS interested in this study are informed when enrollment sites start conducting screening visits. In addition, ALS TDI has created an entry in its clinical trial database that will be updated as new information is confirmed.
Longer Run-In Period and Three Treatment Cycles
Some significant changes are planned for this phase 3 clinical trial compared to the previous trials, including a longer run-in observation period and increases in treatments with NurOwn in the trial from one to three, according to investigators.
To qualify a person with ALS must have experienced their first symptoms of ALS no more than 24 months ago, have a slow vital capacity (breathing test) measure at least 65% of predicted value for their gender, height and age, and meet other enrollment inclusion criteria. While it is not required, those taking a stable dose of riluzole are permitted in the study. Investigators have not been clear if they they will accept individuals taking edaravone into the phase 3 study. Furthermore, people with ALS that are using a feeding tube, bipap or similar interventions at the time of their screening, or those that have had a stem cell treatment before are excluded from this clinical trial.
Image Source: From NEALS Webinar in July 2017, available online. Link below.
The study lasts eleven months in total starting with screening visit to determine if an individual with ALS will qualify. Should a person with ALS qualify, they will be monitored for four months, during which time it should be assumed that various progression measurements will be collected regularly, such as the ALSFRS-R and breathing tests. After the observation period, the individual must qualify again, although it is unclear if this means that all criteria will apply again (ie 24 months, 65%+ SVC, etc).
Those that do re-qualify, we be randomized into either the treatment or control group. One week later, all participants, regardless of which group they are assigned to will undergo bone marrow aspiration. Five weeks after that, each person with ALS will have their first lumbar puncture based delivery of either the NurOwn treated cells or placebo. Two additional treatment/placebo procedures will be conducted eight weeks and 16 weeks after the initial treatment. Three additional months (12 weeks) of observation will round off the trial.
No Updates on Alternative Paths in Canada and Israel
Finally, the company has made several public announcements regarding seeking alternative paths to availability in Israel and Canada for its NurOwn treatment in people with ALS. BrainStorm believes they will gain approval in Israel to offer the treatment to upwards of 50 people with ALS. If there are updates in the meantime, we will report on those.
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