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A phase II open label clinical study of the safety, tolerability and efficacy of ILB ® for Amyotrophic Lateral Sclerosis
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Logan, Ann, Nagy, Zsuzsanna, Barnes, Nicholas M., Belli, Antonio, Di Pietro, Valentina, Tavazzi, Barbara, Lazzarino, Giuseppe, Lazzarino, Giacomo, Bruce, Lars and Persson, Lennart I. (2022) A phase II open label clinical study of the safety, tolerability and efficacy of ILB ® for Amyotrophic Lateral Sclerosis. PLoS One, 17 (5). e0267183. doi:10.1371/journal.pone.0267183 ISSN 1932-6203.
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WRAP-phase-II-open-label-clinical-study-safety-tolerability-efficacy-ILB®-Amyotrophic-Lateral-Sclerosis-Logan-2022.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1121Kb) | Preview |
Official URL: https://doi.org/10.1371/journal.pone.0267183
Abstract
Introduction: Amyotrophic lateral sclerosis (ALS) is an invariably lethal progressive disease, causing degeneration of neurons and muscle. No current treatment halts or reverses disease advance. This single arm, open label, clinical trial in patients with ALS investigated the safety and tolerability of a novel modified low molecular weight dextran sulphate (LMW-DS, named ILB®) previously proven safe for use in healthy volunteers and shown to exert potent neurotrophic effects in pre-clinical studies. Secondary endpoints relate to efficacy and exploratory biomarkers. Methods: Thirteen patients with ALS were treated with 5 weekly subcutaneous injections of ILB®. Safety and efficacy outcome measures were recorded weekly during treatment and at regular intervals for a further 70 days. Functional and laboratory biomarkers were assessed before, during and after treatment. Results: No deaths, serious adverse events or participant withdrawals occurred during or after ILB® treatment and no significant drug-related changes in blood safety markers were evident, demonstrating safety and tolerability of the drug in this cohort of patients with ALS. The PK of ILB® in patients with ALS was similar to that seen in healthy controls. The ILB® injection elicited a transient elevation of plasma Hepatocyte Growth Factor, a neurotrophic and myogenic growth factor. Following the ILB® injections patients reported increased vitality, decreased spasticity and increased mobility. The ALSFRS-R rating improved from 36.31 ± 6.66 to 38.77 ± 6.44 and the Norris rating also improved from 70.61 ± 13.91 to 77.85 ± 14.24 by Day 36. The improvement of functions was associated with a decrease in muscle atrophy biomarkers. These therapeutic benefits decreased 3–4 weeks after the last dosage. Conclusions: This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug’s potential as the first disease modifying treatment for patients with ALS. Trial registration: EudraCT 2017-005065-47.
| Item Type: | Journal Article | ||||||
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| Subjects: | Q Science > QP Physiology R Medicine > R Medicine (General) R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||
| Library of Congress Subject Headings (LCSH): | Amyotrophic lateral sclerosis , Amyotrophic lateral sclerosis -- Patients, Dextran , Clinical trials | ||||||
| Journal or Publication Title: | PLoS One | ||||||
| Publisher: | Public Library of Science | ||||||
| ISSN: | 1932-6203 | ||||||
| Official Date: | 25 May 2022 | ||||||
| Dates: |
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| Volume: | 17 | ||||||
| Number: | 5 | ||||||
| Article Number: | e0267183 | ||||||
| DOI: | 10.1371/journal.pone.0267183 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||
| Date of first compliant deposit: | 2 December 2022 | ||||||
| Date of first compliant Open Access: | 5 December 2022 | ||||||
| RIOXX Funder/Project Grant: |
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