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. 2019 Mar;59(3):303-308.
doi: 10.1002/mus.26385. Epub 2018 Dec 26.

A pilot trial of RNS60 in amyotrophic lateral sclerosis

Sabrina Paganoni  1   2 , Mohamad J Alshikho  1   3 , Sarah Luppino  1 , James Chan  4 , Lindsay Pothier  1 , David Schoenfeld  4 , Patricia L Andres  1 , Suma Babu  1 , Nicole R Zürcher  3 , Marco L Loggia  3 , Robert L Barry  3 , Silvia Luotti  5 , Giovanni Nardo  5 , Maria Chiara Trolese  5 , Serena Pantalone  5 , Caterina Bendotti  5 , Valentina Bonetto  5 , Fabiola De Marchi  1 , Bruce Rosen  3 , Jacob Hooker  3 , Merit Cudkowicz  1 , Nazem Atassi  1
Affiliations

A pilot trial of RNS60 in amyotrophic lateral sclerosis

Sabrina Paganoni et al. Muscle Nerve. 2019 Mar.

Abstract

Introduction: RNS60 is a novel immune-modulatory agent that has shown neuroprotective effects in amytrophic lateral sclerosis (ALS) preclinical models. RNS60 is administered by weekly intravenous infusion and daily nebulization. The objective of this pilot open-label trial was to test the feasibility, safety, and tolerability of long-term RNS60 administration in ALS patients.

Methods: The planned treatment duration was 23 weeks and the primary outcomes were safety and tolerability. Secondary outcomes included PBR28 positron emission tomography (PET) imaging and plasma biomarkers of inflammation.

Results: Sixteen participants with ALS received RNS60 and 13 (81%) completed 23 weeks of RNS60 treatment. There were no serious adverse events and no participants withdrew from the trial due to drug-related adverse events. There were no significant changes in the biomarkers.

Discussion: Long-term RNS60 administration was safe and well-tolerated. A large, multicenter, phase II trial of RNS60 is currently enrolling participants to test the effects of RNS60 on ALS biomarkers and disease progression. Muscle Nerve 59:303-308, 2019.

Keywords: ALS; PBR28; clinical trial; motor neuron disease (MND); neuroinflammation.

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Figures

Figure 1.
Figure 1.. CONSORT diagram: participant enrollment and follow-up for the trial.
Twenty-four volunteers with ALS were assessed for eligibility. Eighteen enrolled in the trial but two were never dosed as they withdrew consent between Screening and Baseline due to unrelated medical problems. The remaining 16 participants received RNS60 and contributed data.
Figure 2.
Figure 2.. [11C]-PBR28 uptake within the Region of Interest (ROI).
Panel A: [11C]-PBR28 uptake (expressed as SUVR60–90min) for each individual participant. Panel B: individual changes in [11C]-PBR28 uptake (expressed as SUVR60–90min) from pre-treatment to post-treatment scans. There were no statistically significant changes in [11C]-PBR28 uptake over the course of the Core Study in the 9 participants who had both pre-treatment and post-treatment scans with boxplot showing median and interquartile range (Wilcoxon signed-rank test; mean change in SUVR60–90min was 0.02 [p= 0.10]).
Figure 3.
Figure 3.. Exploratory inflammatory biomarkers.
Panel A: Individual levels of IL-17 in plasma (N=10). Panel B: individual changes in IL-17 from pre-treatment to post-treatment. There were no statistically significant changes over the course of the study with boxplot showing median and interquartile range (Wilcoxon signed-rank test). Panel C: Individual levels of FOXP3 mRNA expression (a marker of Tregs) in whole blood (N=8). Panel D: individual changes in FOXP3 mRNA expression from pre-treatment to post-treatment. There were no statistically significant changes over the course of the study with boxplot showing median and interquartile range (Wilcoxon signed-rank test).
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