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Is it feasible to remotely collect health data from people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS)? And would doing so help in gauging disease progression among patients?
That&#8217;s what a remote observational study called ALS Go-Digital is now trying to assess.
If validated, the approach could pave the way to fully remote decentralized clinical trials that require little to no travel to study sites. That potentially could significantly increase the number of patients who are willing or able to participate in clinical studies, which, in turn, may accelerate <a href="https://alsnewstoday.com/approved-treatments-for-als/">treatment</a> development.
The ongoing research study, launched in September, is a collaboration between the <a href="https://www.mda.org/">Muscular Dystrophy Association</a> (MDA) and <a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA), which markets the ALS therapies <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> and Radicava ORS.
&#8220;We are excited to be collaborating with Mitsubishi Tanabe Pharma America on this important study,&#8221; Sharon Hesterlee, PhD, chief research officer at the MDA, said in a <a href="https://www.mda.org/press-releases/mda-announces-collaboration-with-mitsubishi-tanabe-pharma-america-for-remote-digital-technology-research-study-for-amyotrophic-lateral-sclerosis-als">press release</a>, adding, &#8220;This could save countless hours and valuable resources which participants must spend at research sites, when they could be spending time with loved ones.”
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<h3>Study tapping into MOVR database to improve remote assessments</h3>
For its part, MTPA said it&#8217;s &#8220;proud&#8221; to work with the U.S.-based nonprofit on this study.
&#8220;MTPA has supported MDA in their work to empower those living with ALS for several years,&#8221; said Yasutoshi Kawakami, MTPA president.
&#8220;Patients are at the forefront of everything we do, and I look forward [to] learning more about how remote data can help support those living with ALS and their caregivers,&#8221; Kawakami said.
ALS is a neurodegenerative condition marked by progressive muscle weakness, which renders patients less able to perform their regular daily activities over time. As the disease progresses, patients&#8217; ability to move on their own and travel also is impaired, so many are not able to participate in clinical trials that require constant in-person monitoring.
Remote assessments could provide an alternative for these patients, enabling more people to participate and posing less of a burden — even for those willing and able to travel long distances to a clinical site.
However, to date, many measurements collected remotely are still not validated as good alternatives to in-person assessments performed by a neurologist.
The researchers in this study aim to address that, with a goal of validating such measurements and determining the best method of data collection for tracking disease progression at a patient&#8217;s own home.
[quote=&#8221;center&#8221;]Repurposing the data collected by MOVR during regular clinic visits lays the foundation to validate and increase acceptance of outcomes for fully remote, decentralized ALS clinical trials, which require little to no travel time on the part of participants.[/quote]
The study is recruiting 75 people from the 2,000 ALS patients currently enrolled in the MDA&#8217;s 10-year-old <a href="https://www.mda.org/science/movr">NeuroMuscular ObserVational Research</a> (MOVR) database, which gathers longitudinal data from patients&#8217; medical records during routine visits to <a href="https://www.mda.org/care/mda-care-centers">MDA Care Centers</a>. There are more than 150 centers across the U.S.
Over one year, digital devices will be used to monitor a number of measures, such as physical activity and sleep, <a href="https://alsnewstoday.com/als-symptoms/">ALS symptoms</a>, and changes in hand and finger dexterity.
Fitbit smartwatches will be used to track daytime physical activity and sleep patterns. The fine motor function of participants&#8217; hands and fingers will be assessed by a proprietary MTPA-developed smartphone app called ALS HANDS. Finally, an app-based electronic Clinical Outcomes Assessment platform will monitor ALS symptoms using self-reported, gold-standard ALS measurements.
This remote data will be paired with the clinical data gathered in the MOVR database to determine if the digital measures are accurate enough to replace some of the clinical measures that are currently employed.
&#8220;Repurposing the data collected by MOVR during regular clinic visits lays the foundation to validate and increase acceptance of outcomes for fully remote, decentralized ALS clinical trials, which require little to no travel time on the part of participants,&#8221; Hesterlee said.

New study testing feasibility of remote data collection for ALS trials

<a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA), which had been testing a once-daily regimen of its oral therapy <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava ORS</a> (edaravone) for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), announced that it is discontinuing the Phase 3b trial and its extension study.
That decision comes after an interim analysis by an independent data monitoring committee (IDMC) showed the once-daily treatment is not likely to work better than the approved on/off regimen.
Still, the IDMC’s recommendation to stop the study was not due to safety or efficacy concerns, and this decision will not impact the commercial availability of Radicava ORS, according to the company.
“Research in ALS has always been extraordinarily difficult, but our continued efforts to advance our knowledge is critical to discover the full potential of oral edaravone as an approved treatment for people with ALS,” Gustavo A. Suarez Zambrano, MD, MTPA’s vice president of medical affairs, said in a <a href="https://www.mt-pharma-america.com/media/news/press-releases/2023/07/31/mitsubishi-tanabe-pharma-america-announces-update-on-global-phase-3b-mt-1186-a02-postmarketing-study-of-oral-edaravone-in-als">company press release</a>.
“We are incredibly grateful to all the study participants, investigators, caregivers and clinical trial staff for their participation, as we remain steadfastly committed to the ALS community,” Suarez Zambrano added.
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<h3>Post-marketing study fulfills MTPA commitment to FDA</h3>
Edaravone, the active ingredient in Radicava and Radicava ORS, is designed to offset oxidative stress, a type of cellular damage implicated in ALS. The therapy aims to prevent damage to motor neurons — nerve cells that control body movement — thereby slowing disease progression.
The into-the-vein (intravenous) formulation of Radicava <a href="https://alsnewstoday.com/news/fda-approves-radicava-first-new-als-therapy-in-20-years-and-cause-for-hope/">earned</a> FDA approval in 2017, and the oral formulation was <a href="https://alsnewstoday.com/news/fda-approves-radicava-ors-oral-suspension-edaravone-als/">approved in the U.S.</a> last year. A liquid suspension taken either orally or via a feeding tube, Radicava ORS was designed to offer the same efficacy as the original therapy but in a more convenient and less burdensome formulation for patients.
Both are given in 28-week or roughly seven-month cycles. In an initial treatment cycle, patients receive daily treatment for 14 consecutive days, followed by two weeks without treatment. Then, the therapies are taken daily over 10 of the next 14 days, followed by another two-week break.
The FDA&#8217;s approval of Radicava ORS was supported by <a href="https://alsnewstoday.com/news/als-treatment-radicava-ors-fares-well-phase-3-clinical-trial/">clinical trial results</a> demonstrating that 105 mg of the oral formulation delivered similar amounts of edaravone to the body and had the same efficacy in slowing disease progression as the 60 mg used in the intravenous version.
The now-discontinued <a href="https://clinicaltrials.gov/ct2/show/NCT04569084">Phase 3b MT-1186-A02 study (NCT04569084)</a> was conducted to fulfill a post-marketing commitment that MTPA made to the FDA after the regulatory agency approved Radicava’s intravenous formulation. It was designed to evaluate the approved Radicava ORS on/off dosing regimen versus once-daily dosing.
The study <a href="https://alsnewstoday.com/news/post-marketing-als-trial-approved-radicava-ors-fully-enrolled/">enrolled 384 ALS patients</a>, ages 18-75, whose symptoms had started less than two years prior. The trial’s main goal was to evaluate changes in disease progression, as assessed by the ALS Functional Rating Scale-Revised (ALSFRS-R), over 48 weeks, or about one year.
The trial&#8217;s IDMC conducted its pre-planned interim analysis after 190 patients — half of the planned study population — reached the 48-week assessment.
Based on the interim data from the primary endpoint, the IDMC concluded that there is a low statistical probability for the once-daily dosing regimen to be more effective than the current on/off regimen. As a result, study discontinuation was recommended.
[quote=&#8221;center&#8221;]Our learnings from this study will support further research, including real-world evidence and biomarker data generation.[/quote]
Nonetheless, the preliminary data did show that the efficacy of the on/off dosing regimen of Radicava ORS was consistent with data from the clinical trials that supported FDA approval of both Radicava formulations. Also, no new safety concerns were reported.
“Our learnings from this study will support further research, including real-world evidence and biomarker data generation,” Suarez Zambrano said.
Supported by the findings, MTPA was released from its post-marketing commitment to the FDA. The company is now notifying trial investigators at study sites of these findings.
MT-1186-A02’s extension study, the <a href="https://classic.clinicaltrials.gov/ct2/show/NCT05151471">Phase 3b MT-1186-A04 trial (NCT05151471)</a>, also will be canceled. Complete trial data will be communicated at a future date, the company noted in its release.

MTPA to stop Phase 3 trial of approved Radicava ORS for ALS

Note: This story was updated March 10, 2023, to correct a secondary headline to note the therapy was tracked for less than a year. The story also clarifies the timing of results from a Phase 3 clinical trial and that edaravone is believed to reduce oxidative stress.
Radicava ORS, an oral formulation of <a href="https://alsnewstoday.com/radicava-edaravone-for-als/">Radicava</a> (edaravone), was well tolerated among people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) over nearly a year of treatment in a clinical trial.
Findings from the trial had <a href="https://alsnewstoday.com/news/edaravone-oral-form-shows-good-tolerability-over-one-year-use/">been announced </a><a href="https://alsnewstoday.com/news/edaravone-oral-form-shows-good-tolerability-over-one-year-use/">previously</a> by the therapy&#8217;s developer <a href="https://www.mt-pharma-america.com/">Mitsubishi Tanabe Pharma America</a> (MTPA), and 24-week data from the trial helped form the basis of the U.S. Food and Drug Administration (FDA)&#8217;s <a href="https://alsnewstoday.com/news/fda-approves-radicava-ors-oral-suspension-edaravone-als/">approval of Radicava ORS last year</a>.
The results have now undergone peer review and were detailed in the study, &#8220;<a href="https://onlinelibrary.wiley.com/doi/full/10.1002/mus.27768">Oral edaravone demonstrated a favorable safety profile in patients with amyotrophic lateral sclerosis after 48 weeks of treatment</a>,&#8221; published in <a href="https://onlinelibrary.wiley.com/journal/10974598">Muscle &amp; Nerve</a>. The work was funded by MTPA.
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&#8220;We&#8217;re encouraged by the data that we continue to collect from the global Phase 3 trial of Radicava ORS, demonstrating a favorable safety profile after 48 weeks of treatment,&#8221; Gustavo Suarez Zambrano, MD, vice resident of medical affairs at MTPA, said in a <a href="https://www.prnewswire.com/news-releases/mitsubishi-tanabe-pharma-america-announces-48-week-results-from-global-open-label-phase-3-trial-of-radicava-ors-edaravone-in-als-301756250.html">press release</a>. &#8220;These data build upon the study&#8217;s 24-week findings that supported the FDA approval of Radicava ORS.&#8221;
While the mechanism of action of edaravone, the active agent in Radicava and Radicava ORS, is unknown, it is believed to reduce oxidative stress — a type of cell damage that’s thought to play a critical role in driving <a href="https://alsnewstoday.com/causes-of-als/">nerve cell death in ALS</a>. The original therapy was designed to be delivered intravenously (via infusion into the bloodstream), and results from clinical trials showed that it <a href="https://alsnewstoday.com/news-posts/2020/03/30/radicava-effective-slowing-als-progression-across-1-year-use-patients-trial-data/">slowed functional decline</a> in people with early ALS.
Radicava ORS was designed to deliver the same active ingredient, but in an oral form that would be more convenient for patients. Pharmacological studies have demonstrated that a 105 mg dose of oral Radicava ORS delivers the same amount of edaravone as the approved 60 mg dose of intravenous Radicava. MTPA conducted a <a href="https://clinicaltrials.gov/ct2/show/NCT04165824">Phase 3 clinical trial (NCT04165824)</a> aiming to assess the safety of the oral formulation.
The study enrolled 185 adults <a href="https://alsnewstoday.com/als-diagnosis/">diagnosed with ALS</a> at sites in the U.S., Canada, Japan, Germany, France, and Italy. The average participant age was around 60 years, and the average disease duration was about 1.5 years. About 80% of patients had <a href="https://alsnewstoday.com/forms-of-als/">limb-onset disease</a>, while the rest had bulbar-onset.
<h3>Four-week cycles</h3>
All of the patients were treated with Radicava ORS, administered in four-week treatment cycles similar to how the intravenous formulation is given: two weeks of taking the therapy, and then two weeks off in the first cycle, and then 10 days of treatment in the first two weeks, followed by two weeks off in subsequent cycles.
Most of the patients (87%) also were being treated with riluzole (sold as <a href="https://alsnewstoday.com/als-treatment/rilutek-riluzole/">Rilutek</a> and other formulations), and nearly one in five (18.4%) had been on intravenous Radicava previously.
The study lasted 48 weeks (almost a year). About 25% of the participants did not complete the full 48 weeks of treatment, mainly due to experiencing safety issues, death due to ALS, or due to the patient&#8217;s choice. The researchers said this rate is &#8220;comparable with or slightly lower than other recent clinical trials in ALS.&#8221;
Safety-related events were reported in nearly every participant over the course of the study, though many of these events were judged to be a result of ALS disease progression and not considered related to treatment with Radicava ORS.
By 48 weeks, about one quarter (24.9%) of the participants had experienced safety-related events that were judged by study investigators to be likely side effects of the oral therapy. The most common side effects were fatigue, dizziness, headache, and constipation. No treatment-related side effects were judged to be serious.
<h3>Findings consistent with IV Radicava</h3>
These findings were generally consistent with the known safety profile of intravenous Radicava, the researchers said.
&#8220;The 48-week results from this trial suggest that RADICAVA ORS was well tolerated, and support its long-term use as a treatment for ALS. Our hope is for these data to provide additional information to physicians who are considering this oral treatment option for their patients,&#8221; said Gary Pattee, MD, a neurologist and ALS specialist who works in Nebraska.
Over the course of the study, the average forced vital capacity (FVC) — a standardized measure of lung function based on how much someone can forcibly exhale — decreased by an average of 25.1%. Again, the researchers said this is consistent with prior trial results for intravenous Radicava, where the average decline in FVC was 15.6% for those on therapy, compared to 20.4% for patients given a placebo.
&#8220;This trial provides safety data to support the use of oral [Radicava ORS], which expands on existing evidence supporting the use of FDA-approved [intravenous Radicava] and the recently approved oral suspension formulation,&#8221; the scientists concluded.

Tag: MTPA

New study testing feasibility of remote data collection for ALS trials

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