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Enrollment is complete in a Phase 2 trial testing <a href="https://inflectisbioscience.com/">InFlectis BioScience</a>’s oral candidate IFB-088 (icerguastat) in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), the company has announced.
The <a href="https://clinicaltrials.gov/study/NCT05508074">trial (NCT05508074)</a> enrolled a total of 50 adults with bulbar-onset ALS, a form of the disease that first affects the muscles in the head and neck, leading to swallowing, chewing, and speech difficulties.
Participants were randomly assigned to receive IFB-088 or a placebo, given as an add-on to <a href="https://alsnewstoday.com/rilutek-riluzole-for-als/">riluzole</a>, an approved ALS therapy sold as Rilutek, Tiglutik, or Exservan. Treatment will be given twice a daily for six months, and early results might be presented later this year.
“We dosed the first patient in December 2022 and randomized the last patient on January 30, 2024,” Anne Visbecq, MD, InFlectis’ chief medical officer, said in a <a href="https://inflectisbioscience.reportablenews.com/pr/inflectis-completes-enrollment-phase-2-trial-of-ifb-088-in-als">company press release</a>. “Following the six-month treatment period, we look forward to reporting our initial findings as early as the end of this year.”
[recommended-reading id=88241]
<h3>Phase 2 trial results will determine timing, scope of potential global study</h3>
“These results will determine the timing and scope of a potential global registration study in the overall ALS population,” Visbecq added.
ALS is characterized by the progressive dysfunction and death of motor neurons, the nerve cells that control voluntary movements. About one-third of patients have <a href="https://alsnewstoday.com/forms-of-als/">bulbar-onset ALS</a>, which is more aggressive and has a shorter life expectancy than limb-onset ALS, in which first symptoms are associated with weakness in the muscles of the arms and hands, or legs and feet.
IFB-088 is an orally available small molecule capable of crossing the blood-brain barrier, a cell layer that protects the brain from disease-causing agents and toxins that may be present in the blood.
The medication inhibits the PPP1R15A/PP1c protein complex to keep a natural cellular stress-response mechanism active. This is thought to give stressed cells additional time to correct their protein imbalances and eliminate protein clumps, a hallmark of ALS that contributes to neurodegeneration.
IFB-088 also serves as an inhibitor of certain glutamate receptors. These receptors are involved in a process called excitotoxicity, in which neurons are over-stimulated and fire much more than needed, leading to nerve damage.
An earlier <a href="https://clinicaltrials.gov/study/NCT03610334">Phase 1 trial (NCT03610334)</a> involving healthy volunteers showed the investigational therapy is generally safe and well tolerated. The therapy was given at doses ranging from 2.5 mg to 60 mg daily, and no reports of serious adverse events or dose-limiting toxicities were reported.
The ongoing Phase 2 trial enrolled 50 patients at sites in France and Italy who are receiving 50 mg daily of IFB-088 — given as two oral 25 mg capsules 12 hours apart and 30 minutes before a meal — or a placebo, for 26 weeks. All are also taking riluzole in the form of tablets (Rilutek and generics) or a suspension formulation (<a href="https://alsnewstoday.com/tiglutik-for-als/">Tiglutik</a>) at a daily dose of 100 mg, given as two 50 mg doses every 12 hours.
[recommended-reading id=89682]
<h3>Trial to examine IFB-088&#8217;s safety, ability to slow functional decline in patients</h3>
The trial’s main goal is to assess the treatment&#8217;s safety and tolerability, but researchers will also examine if the therapy can slow patients’ functional decline, reflected by changes in the ALS Functional Rating Scale-Revised.
Two <a href="https://alsnewstoday.com/stages-of-als/">staging systems</a> — the King’s College and the Milano-Torino systems — will also be used to assess changes in patients&#8217; clinical progression and treatment response. The therapy’s effect on the patient&#8217;s quality of life and disease-related blood biomarkers will also be assessed.
“This trial reflects our commitment to bring a novel molecule with a unique mode of action to ALS patients, starting with patients suffering from bulbar-onset ALS, the most aggressive form of the disease,” Visbecq said.
IFB-088&#8217;s development and the Phase 2 trial were financially supported by the <a href="https://www.als.org/">ALS Association</a>, AFM-Téléthon (a French patient organization fighting rare neuromuscular diseases), and Bpifrance (the French public bank of investment). The <a href="https://alsnewstoday.com/news/inflectis-okd-to-start-phase-2-trial-of-ifb-088-for-bulbar-onset-als/">trial was approved</a> in 2022 by the French health authority ANSM.
Also in 2022, IFB-088 was granted <a href="https://alsnewstoday.com/news/inflectis-ifb-088-orphan-drug-status-fda-als-treatment/">orphan drug designation</a> by the U.S. Food and Drug Administration. The designation is meant to accelerate IFB-088’s clinical development and review by providing regulatory support and financial benefits, and a seven-year marketing exclusivity if the therapy is ultimately approved.

Phase 2 trial of oral IFB-088 for bulbar-onset ALS now fully enrolled

A Phase 2b trial of PrimeC for people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) has completed patient enrollment, according to <a href="https://www.neurosense-tx.com/">NeuroSense Therapeutics</a>, the therapy&#8217;s developer.
Called <a href="https://clinicaltrials.gov/ct2/show/NCT05357950">PARADIGM (NCT05357950)</a>, the study enrolled 69 adults <a href="https://alsnewstoday.com/als-diagnosis/">diagnosed with ALS</a>, ages 18-75, at sites in Israel, Italy, and Canada. The company anticipates top-line results late this year.
The trial is testing an extended-release formulation of PrimeC, designed to require less frequent dosing for patients.
“Based on the new formulation, we are aiming for efficacy and safety results that will meet and exceed the results achieved in the Phase 2a study,” Vivian Drory, MD, principal investigator of the PARADIGM trial at Tel Aviv Sourasky Medical Center, in Israel, said in a <a href="https://www.prnewswire.com/news-releases/neurosense-completes-enrollment-in-phase-2b-als-clinical-trial-301824559.html">company press release</a>.
Results from this study will inform the design of a future pivotal Phase 3 clinical trial of PrimeC, the company said.
[recommended-reading id=78033]
<h3>PARADIGM trial testing 17 outcome measures for Prime C</h3>
PrimeC is an oral, fixed-dose combination of two medications approved in the U.S. that both have well-established safety profiles. One, ciprofloxacin, is an antibiotic, while the other, celecoxib, is an anti-inflammatory agent.
The combination is thought to potentially inhibit disease progression by targeting key mechanisms in ALS motor degeneration. Specifically, the therapy aims to block inflammation, iron accumulation, and impaired RNA processing.
An initial formulation of PrimeC was found to be <a href="https://alsnewstoday.com/news/primec-safe-lowers-als-disease-biomarkers-phase-2-clinical-study/">safe and well tolerated</a>, and showed some promising trends toward less functional and respiratory decline, in a previous <a href="https://clinicaltrials.gov/ct2/show/NCT04165850">Phase 2a trial (NCT04165850)</a>. That trial involved 15 ALS patients.
The PARADIGM trial was designed to test a longer-acting formulation of PrimeC, which may be administered less frequently because it releases the two medications over an extended period of time.
The trial enrolled ALS patients whose symptoms of muscle weakness began less then 30 months (about 2.5 years) before screening. All participants were randomly assigned to receive Prime C, at a total daily dose of 1,496 mg — two tablets twice daily — or a placebo, for six months. All patients maintained their standard <a href="https://alsnewstoday.com/als-treatment/">ALS medication</a> regimen during the trial.
The study primarily aims to evaluate the treatment&#8217;s safety and tolerability, as well as changes in ALS biomarkers associated with PrimeC treatment. Secondary measures include changes in patients&#8217; functional disability, lung function, quality of life, and survival.
“PARADIGM is tracking 17 different outcome measures while the primary endpoint remains focused on biomarkers,“ said Ferenc Tracik, MD, chief medical officer at NeuroSense.
“This wealth of outcome data will not only be used to optimize the design of a future pivotal Phase 3 study for PrimeC, but we believe it will provide greater insight into the mechanisms of ALS for the scientific community as we advance toward a day when ALS will become a highly treatable disease,&#8221; Tracik said.
After completing the trial’s randomized phase, patients will have the option to enter an open-label extension phase, during which all participants will receive PrimeC for one year. To date, 26 participants completed the randomized phase, and 25 chose to continue into the extension part.
&#8220;It is highly encouraging that nearly all participants who completed the study have elected to continue in the [open label extension] phase with the treatment of PrimeC,&#8221; Drory said.
&#8220;We look forward to seeing the topline data from this study,&#8221; Drory added, noting the trial is testing the &#8220;optimized formulation of PrimeC.&#8221;
PrimeC has been granted orphan drug status in both the U.S. and the European Union. This designation is awarded to therapies that aim to treat rare diseases.
&#8220;We are pleased to share this milestone for the PARADIGM clinical trial,&#8221; said Alon Ben-Noon, CEO of NeuroSense, adding, &#8220;We are grateful to the participants living with ALS, their families, and the study investigators for their commitment to the PARADIGM trial and for taking part in our mission to develop an effective therapy for ALS.&#8221;

PARADIGM trial of PrimeC for ALS now fully enrolled with 69 adults

<a href="https://seelostherapeutics.com/">Seelos Therapeutics</a> has finished enrolling patients in its Phase 2/3 clinical trial of <a href="https://seelostherapeutics.com/sls-005-trehalose/">SLS-005</a> to treat <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS), the company announced.
The <a href="https://clinicaltrials.gov/ct2/show/NCT05136885">ongoing trial (NCT05136885)</a> recruited 160 patients with <a href="https://alsnewstoday.com/forms-of-als/familial-als/">familial</a> and <a href="https://alsnewstoday.com/forms-of-als/sporadic-als/">sporadic ALS</a>, and top-line results are expected by the second half of 2023.
This is the fifth arm of the <a href="https://clinicaltrials.gov/ct2/show/NCT04297683?term=HEALEY+ALS&amp;draw=2&amp;rank=1">HEALEY platform trial (NCT04297683)</a>, which is being led by researchers at the Sean M. Healey &amp; AMG Center for ALS at Massachusetts General Hospital (MGH), Boston to investigate several ALS therapies simultaneously against a shared placebo group.
The company also expects to launch an <a href="https://alsnewstoday.com/news/funding-expands-access-seelos-investigational-als-therapy-sls-005/">expanded access program</a> (EAP) in the coming months to give people with ALS who aren&#8217;t eligible for clinical trials the opportunity to access SLS-005. The EAP will include 70 participants who&#8217;ll receive the experimental therapy for 24 weeks. <a href="https://seelostherapeutics.com/patients-and-caregivers/">More information</a> is available at Seelos&#8217; website.
&#8220;The full enrollment of this study is a significant milestone for Seelos. We look forward to releasing the top-line data later this year and initiating the Expanded Access Program later this quarter,&#8221; said Raj Mehra, PhD, Seelos’ chairman and CEO, in a <a href="https://www.prnewswire.com/news-releases/seelos-therapeutics-announces-completion-of-enrollment-of-its-phase-iiiii-trial-of-sls-005-in-amyotrophic-lateral-sclerosis-on-the-healey-als-platform-301744494.html">company press release</a>.
EAP will be funded by a grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the <a href="https://alsnewstoday.com/news/landmark-act-for-als-act-president-biden/">Accelerating Access to Critical Therapies for ALS Act</a> (ACT for ALS).
&#8220;We would like to offer our gratitude to the ALS community for its support and to the team at Healey &amp; AMG Center for ALS at Mass General and the clinical trial sites in the Northeast ALS Consortium for their hard work and commitment in running this innovative platform trial. We also thank the NINDS for the financial support of the Expanded Access Program grant under the ACT for ALS,&#8221; Mehra said.
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<h3>SLS-005 promotes protein clearance</h3>
SLS-005 is made of a natural sugar molecule called trehalose that can enter the brain and promote autophagy, the process by which cells break down and recycle old or faulty proteins they no longer need, preventing their toxic buildup.
Administered directly into the bloodstream, SLS-005 has been shown to lower faulty proteins&#8217; aggregation and reduce the accumulation of toxic clumps in animal models of neurodegenerative conditions.
In ALS models, it promoted the clearance of TDP-43 and SOD1 proteins, which are known to accumulate to toxic levels and contribute to nerve cell death. By doing so, the treatment was able to prevent nerve cell loss and delay disease progression in these models.
SLS-005 received orphan drug status — a designation that&#8217;s intended to speed the development and review of therapies for life-threatening rare diseases — in both <a href="https://alsnewstoday.com/news-posts/2020/11/20/fda-grants-orphan-drug-designation-to-seelos-sls-005-for-treating-als/">the U.S.</a> and the <a href="https://alsnewstoday.com/news-posts/2021/06/04/ema-orphan-drug-designation-sls-005-als/">European Union</a>.
In the SLS-005 arm of the HEALEY ALS platform trial, participants were randomly assigned to weekly intravenous (into-the-vein) injections of SLS-005 or a placebo for 24 weeks (about six months). The patients were randomized in a 3:1 ratio, meaning for each patient assigned a placebo, three were given SLS-005.
The trial’s main goal is to evaluate whether SLS-005 slows disease progression, as measured with the ALS Functional Rating Scale Revised (ALSFRS-R). Secondary goals include changes in lung function, muscle strength, and quality of life, as well as symptoms of disease progression.
Other treatments being investigated in the HEALEY trial include Prilenia Therapeutic’s pridopidine <a href="https://clinicaltrials.gov/ct2/show/NCT04615923">(NCT04615923)</a> and Clene Nanomedicine‘s CNM-Au8 <a href="https://clinicaltrials.gov/ct2/show/NCT04414345">(NCT04414345)</a>.
Another regimen, UCB’s zilucoplan <a href="https://clinicaltrials.gov/ct2/show/NCT04436497">(NCT04436497)</a>, was <a href="https://alsnewstoday.com/news/ucb-stops-zilucoplan-arm-early-healey-trial-als-lack-of-efficacy/">discontinued in March 2022</a> due to a lack of effectiveness in an interim analysis. Biohaven Pharmaceuticals’ verdiperstat <a href="https://clinicaltrials.gov/ct2/show/NCT04436510">(NCT04436510)</a> also <a href="https://alsnewstoday.com/news/als-therapy-verdiperstat-fails-healey-trial-efficacy-goals/">failed to meet</a> its primary and secondary goals.

Enrollment complete in HEALEY Phase 2/3 trial arm of SLS-005

A large Phase 3 trial designed to confirm the safety and efficacy of the approved therapy <a href="https://alsnewstoday.com/amx0035/">Relyvrio</a> (sodium phenylbutyrate and taurursodiol) for <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) is now fully enrolled.
<a href="https://www.amylyx.com/">Amylyx Pharmaceuticals</a> announced the completion of patient recruiting for the trial, called <a href="https://clinicaltrials.gov/ct2/show/NCT05021536">PHOENIX (NCT05021536)</a>, which will test the oral therapy in a total of 664 people at dozens of sites across the U.S. and Europe. Top-line data is expected in 2024.
“We are grateful for the people living with ALS and their families who are participating in PHOENIX and the dedication of the study investigators,” Joshua Cohen and Justin Klee, co-CEOs of Amylyx, said in a <a href="https://www.businesswire.com/news/home/20230202005258/en/Amylyx-Pharmaceuticals-Announces-Completion-of-Enrollment-in-Global-Phase-3-PHOENIX-Trial-of-AMX0035-in-ALS">company press release</a>.
“We remain committed to continuing research and exploring the full potential of [Relyvrio] as part of our mission to one day end the suffering caused by ALS and other neurodegenerative diseases,” they added.
Relyvrio, formerly called AMX0035, is a fixed-dose combination of two compounds — tauroursodeoxycholic acid and sodium phenylbutyrate — that block stress signals involved in nerve cell damage and ALS progression.
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<h3>Confirming the effectiveness of Relyvrio post-approval</h3>
The treatment&#8217;s effectiveness and safety was originally investigated in a Phase 2 clinical trial called <a href="https://clinicaltrials.gov/ct2/show/NCT03127514">CENTAUR (NCT03127514)</a>. That trial, completed in 2019, involved 137 adults with recently diagnosed and rapidly progressing ALS.
The results showed that Relyvrio significantly <a href="https://alsnewstoday.com/news-posts/2020/09/03/amx0035-safe-effective-in-slowing-als-functional-decline-trial-data-shows/">slowed functional decline</a> and <a href="https://alsnewstoday.com/news-posts/2020/10/19/amylyxs-amx0035-significantly-extends-als-patients-lives-long-term-trial-data-show-also-slows-functional-decline/">extended survival</a>, compared with a placebo.
Amylyx used that data to support its application for Relyvrio&#8217;s <a href="https://alsnewstoday.com/news/relyvrio-amx0035-approved-us-als-treatment/">approval in the U.S.</a> and its <a href="https://alsnewstoday.com/news/amx0035-oral-als-therapy-called-albrioza-approved-canada/">conditional approval in Canada</a> — where the therapy is marketed under the brand name Albrioza. In Canada, more data is needed to support full regulatory approval of Relyvrio.
The PHOENIX trial was designed to confirm results from CENTAUR in a larger group of ALS patients. Participants are randomly assigned to receive Relyvrio or a placebo for 48 weeks (about one year), followed by open-label treatment for up to two years. In the open-label part, both patients and researchers know exactly what therapy participants are receiving/
The trial’s main goals are to assess the therapy&#8217;s safety and changes in the rate of functional decline, as measured with the ALS Functional Rating Scale-Revised (ALSFRS-R). Other goals include changes in lung function, quality of life, and survival.
[quote align=&#8221;center&#8221;]We anticipate that PHOENIX will help us generate further data about the safety and efficacy of [Relyvrio].[/quote]
The study is being conducted at 69 sites in the U.S. and Europe as part of collaborations with the Northeast ALS Consortium (NEALS) and the Treatment Research Initiative to Cure ALS (TRICALS), respectively.
“The Phase 3 PHOENIX trial [is] an excellent collaboration between European and United States Centers for excellence in ALS research and care,” said Leonard H. van den Berg, MD, PhD, professor of neurology at the University Medical Center Utrecht and chair of the TRICALS.
&#8220;We anticipate that PHOENIX will help us generate further data about the safety and efficacy of AMX0035,&#8221; van den Berg added.
The trial is expected to conclude in 2024 and its results could further support Amylyx’s regulatory applications — including in Europe, where the medication is <a href="https://alsnewstoday.com/news/amylyxs-amx0035-now-under-review-approval-europe/">under regulatory review</a>. Amylyx expects a decision from the European Medicines Agency in the first half of 2023.
The company said the results of the ongoing trial also would likely be needed for full approval of the therapy in the European Union if conditional marketing authorization is granted.
“We are pleased to share this milestone from the PHOENIX trial, a collaborative effort to advance our scientific understanding of ALS and build upon the positive data from our Phase 2 CENTAUR trial,” said Sabrina Paganoni, MD, PhD, principal investigator of CENTAUR and a member of the NEAL&#8217;s executive committee.
Relyvrio also is being tested as a potential treatment of other neurodegenerative conditions, such as <a href="https://alzheimersnewstoday.com/what-is-alzheimers-disease/">Alzheimer’s disease</a> and Wolfram syndrome.

Tag: patient enrollment

Phase 2 trial of oral IFB-088 for bulbar-onset ALS now fully enrolled

PARADIGM trial of PrimeC for ALS now fully enrolled with 69 adults

Enrollment complete in HEALEY Phase 2/3 trial arm of SLS-005

Enrollment complete in new trial of approved ALS therapy Relyvrio