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Interim results from an open-label, single-center, hybrid-virtual 12-month trial of a Lunasin regimen for patients with Amyotrophic Lateral Sclerosis (BW28)

RS Bedlack,1 Alicia Spector,2 Elizabeth Morgan,2 Paul Wicks,2Timothy Vaughan, 2 Amanda Dios3, Ghazaleh Sadri-Vakili,3

1. VA and Duke University Medical Centers - Durham NC, USA2. PatientsLikeMe-Cambridge MA, USA

3. MassGeneral Institute for Neurodegenerative Diseases-Charlestown MA, USA

Background

Enrollment & Retention

Lunasin, a soy peptide that may alter histone acetylation, has been associated with an ALS reversal. We recently finished enrollment in a patient-centric pilot trial of Lunasin. The hypotheses we are testing were described at last year’s meeting. Here we present our interim results as of 11/1/16.

Perceived Burdens and Efficacy

Acknowledgements

We enrolled 50 participants in 5.5 months for an enrollment rate of 9.1 participants per site per month. Participants are primarily white (94%) males (58%) and have a mean age of 60 and disease duration of 4 years. Eleven participants have dropped out of the study, 4 due to adverse events, 4 due to study burdens or perceived lack of efficacy, 3 due to deaths (assessed as unrelated to study).

Biomarkers

We thank the many ALS patients and families who contributed funds to support this study, especially the Larry Vance Hughes ALS Foundation. We thank Reliv for donating the Lunasin products.

Agreement between coordinator and participant-obtained ALSFRS-R scores at month 1. Another comparison of scores will be made at 12 months.

ALSFRS Agreement

MethodsLunasin treatment associated with altered histones in patient peripheral blood mononuclear cells. (A) Histone H3 levels were significantly decreased in peripheral blood mononuclear cells (PBMCs) following 1 month of Lunasin treatment (p=0.026, Wilcoxon matched-paired signed rank test). Cleaved 15 kd H3 fragment was higher in the treated group, but not at a statistically significant level (p=0.209) (B) There was no change in H3K9K14ac2 (AcH3) levels following Lunasin treatment and although not statistically significant, the levels of the cleaved 15 kd AcH3 fragment was higher (p=0.207) (C) While there was no change in H4K4K7K10K14ac4 (AcH4), there was a significant increase in the cleaved 15 kd AcH4 fragment (p=0.029, Wilcoxon matched-paired signed rank test). N = 42; * p<0.05. We are currently testing controls to better understand the meaning of these findings.

This a widely inclusive, largely virtual, open label trial of a supplement regimen we refer to as Lunasin. Participants make 3 visits to Duke (Screening/Baseline, Month 1 and Month 12). During these they are taught to measure ALSFRS-R and weight, to use the PatientsLikeMe website (PLM), and we draw blood to assess pharmcodynamic biomarkers. At months 2-11, participants make “virtual visits” measuring their own ALSFRS-R score and weight, and logging onto PLM to record it as well as perceived efficacy, compliance, adverse events and changes in concomitant medications. Participants are compared to matched historical controls from PLM, generated using pre-treatment ALSFRS-R progression rates, as previously described (Nature Biotech 2011;29:411).

Safety & TolerabilitySAE and AE thus far (all unexpected).

AdherenceParticipant ratings of treatment adherence. Coordinator-obtained measures of compliance will be reported in late 2017 after study completion.

Data DensityNumber of participants reaching various time points, and the percentage that are compliant with outcome measure entry.

Event Number Experiencing Type Related?Obstipation/Fecal Impaction 2 SAE Possibly

Death from Disease Progression 2 SAE Unrelated

Death from Cardiac Arrest 1 SAE Unrelated

Death from ICH 1 SAE UnrelatedPEG Infection 1 SAE UnlikelyC. diff. Infection 1 SAE UnlikelyConstipation 11 AE PossiblyFullness/Early Satiety 6 AE PossiblyIncreased Progression 2 AE UnlikelyItching 2 AE UnlikelyNausea 2 AE Possibly

Increased Appetite 1 AE UnlikelyDecreased Appetite 1 AE UnlikelyHyperglycemia 1 AE UnlikelyIrritated Hiatal Hernia 1 AE UnlikelyFall 1 AE UnlikelyConfusion 1 AE UnlikelyProstate Enlargement 1 AE UnlikelyRestless arm movements 1 AE Unlikely

Increased Fasciculations 1 AE Unlikely

UTI 1 AE UnlikelyIncreased Cramps 1 AE UnlikelyIncreased PBA 1 AE UnlikelyBreast Tenderness 1 AE UnlikelyDiarrhea 1 AE Possibly“Heaviness” 1 AE UnlikelyFlatulence 1 AE PossiblyMumps 1 AE UnrelatedEarache 1 AE UnlikelyWeight Gain 1 AE Unlikely

Participant ratings of side effect severity this far.

Participant ratings of burdens (left) and efficacy (right) this far. Additional measures will be obtained at the end of the trial in late 2017.