A Study of NE3107 in Early Parkinson's

A unitless inflammatory biomarker calculated by dividing the absolute peripheral blood monocyte count by the absolute peripheral blood lymphocyte count, using values derived from clinical hematology (complete blood count with differential)

A unitless measure of systemic inflammation calculated as the product of the absolute blood neutrophil count and absolute blood monocyte count divided by the absolute blood lymphocyte count in samples obtained for clinical hematology testing.

A unitless measure of systemic inflammation calculated as the ratio of the absolute peripheral blood neutrophil count to the absolute peripheral blood lymphocyte count obtained from routine clinical hematology assessments.

A unitless composite measure of systemic inflammation and immune status calculated as the product of the absolute peripheral blood platelet count and neutrophil count divided by the absolute peripheral blood lymphocyte count obtained from routine clinical hematology assessments.

A unitless measure of systemic inflammation calculated as the ratio of the absolute peripheral blood platelet count to the absolute peripheral blood lymphocyte count obtained from routine clinical hematology assessments.

A unitless composite measure of systemic inflammation calculated as the product of the absolute peripheral blood neutrophil count, monocyte count, and platelet count divided by the absolute peripheral blood lymphocyte count obtained from routine clinical hematology assessments.

Early Parkinson's Neuro-Inflammatory Composite-15 (EPNIC-15), a composite endpoint consisting of 15 clinically relevant motor and non-motor measures derived from MDS-UPDRS Parts I, II, and III and PDSS-2 assessments. Lower scores indicate improvement in Parkinson's disease symptoms.

Change from baseline in MDS-UPDRS Modified Part III score, a clinician-rated measure of Parkinson's disease motor signs assessed using a modified Part III examination. The scale evaluates motor manifestations including speech, tremor, rigidity, bradykinesia, gait, posture, and postural stability. Higher scores indicate worse motor impairment.

Change from baseline in MDS-UPDRS Part II score. MDS-UPDRS Part II assesses the impact of Parkinson's disease motor symptoms on activities of daily living, with higher scores indicating greater impairment and negative changes indicating improvement.

Change from baseline in MDS-UPDRS Part I score. MDS-UPDRS Part I assesses non-motor experiences of daily living in Parkinson's disease, with higher scores indicating greater symptom burden and negative changes indicating improvement.

Change from baseline in the combined MDS-UPDRS score (Parts I + II + III). The combined score assesses overall Parkinson's disease burden across non-motor symptoms, activities of daily living, and motor signs, with higher scores indicating greater impairment and negative changes indicating improvement.

Change from baseline in PDQ-39 total score. The Parkinson's Disease Questionnaire-39 (PDQ-39) assesses health-related quality of life across eight domains affected by Parkinson's disease. Higher scores indicate worse quality of life and negative changes indicate improvement.

Clinician's Global Impression of Improvement (CGI-I) score. The CGI-I is a clinician-rated measure of overall change in a participant's condition compared with baseline, scored on a 7-point scale from 1 (very much improved) to 7 (very much worse). Lower scores indicate greater improvement.

Change from baseline in Clinician's Global Impression of Severity (CGI-S) score. The CGI-S is a clinician-rated measure of overall illness severity scored on a 7-point scale from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Higher scores indicate greater severity and negative changes indicate improvement.

Change from baseline in modified PARCOMS-Motor score. PARCOMS-Motor is a composite measure of Parkinson's disease motor symptoms derived from MDS-UPDRS motor assessments. The score was modified to adjust for missing MDS-UPDRS Part III data. Higher scores indicate greater motor impairment and negative changes indicate improvement

Change from baseline in PDSS-2 total score. The Parkinson's Disease Sleep Scale-2 (PDSS-2) assesses sleep disturbances and nocturnal symptoms associated with Parkinson's disease. Higher scores indicate worse sleep impairment and negative changes indicate improvement.

Change from baseline in DNA methylation levels measured in peripheral blood samples. DNA methylation is an epigenetic biomarker associated with regulation of gene expression and cellular function.

Percent change from baseline in hematologic inflammatory biomarker indices (MLR, NLR, PLR, SIRI, SII, and AISI) derived from routine hematology testing. These indices are calculated from peripheral blood cell counts and are used as measures of systemic inflammation.

Change from baseline in plasma biomarkers of inflammation measured in peripheral blood samples. Plasma inflammatory biomarkers are indicators of immune and inflammatory activity that may reflect biological responses to treatment.

Interaction between baseline inflammation level and treatment effect on changes in circulating inflammatory indices. Analysis of whether treatment effects on MLR, NLR, PLR, SIRI, SII, and AISI vary according to baseline systemic inflammation status.

Interaction between baseline inflammation level and treatment effect on changes in clinical endpoints. Analysis of whether treatment effects on clinical measures vary according to baseline systemic inflammation status.

Relationship between change in inflammation level and change from baseline in circulating inflammatory indices (MLR, NLR, PLR, SIRI, SII, and AISI). Analysis of whether treatment-related changes in systemic inflammation are associated with changes in circulating inflammatory biomarkers.

Relationship between change in inflammation level and change from baseline in clinical endpoints. Analysis of whether treatment-related changes in systemic inflammation are associated with changes in clinical measures of Parkinson's disease.

Percent of participants with improvement on CGI-I. Improvement is defined as a CGI-I score of 1 (very much improved), 2 (much improved), or 3 (minimally improved). The CGI-I is a clinician-rated measure of overall change from baseline

Percent of participants with improvement in CGI-S score from baseline. Improvement is defined as any decrease from baseline in the Clinician's Global Impression of Severity (CGI-S) score. The CGI-S is a clinician-rated measure of overall illness severity scored from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Lower scores indicate less severe illness.

Biological and disease phenotype subgroup analyses of changes in circulating inflammatory biomarker indices (MLR, NLR, PLR, SIRI, SII, and AISI). Analyses will evaluate whether treatment-related changes in inflammatory biomarkers differ across predefined biological and disease phenotype subgroups.

Biological and disease phenotype subgroup analyses of changes in clinical endpoints. Analyses will evaluate whether treatment-related changes in clinical outcome measures differ across predefined biological and disease phenotype subgroups.