Trial Outcomes & Findings for Early Parkinson's Disease Monotherapy With CVN424 (NCT NCT06006247)

This is a randomized, parallel-group, double-blind, placebo-controlled clinical trial of CVN424 in early, untreated Parkinson's Disease (PD). This study evaluated the potential of CVN424 to improve motor and non-motor functions in individuals with early PD not taking dopaminergic or anti-PD therapies.

A total of 64 participants were enrolled in the study.

Early Parkinson's Disease Monotherapy With CVN424

MDS-UPDRS was a comprehensive 50-question assessment designed to evaluate both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals with PD and their caregivers, as well as sections that were consistently completed by the same approved rater throughout the study. Parts II and III were used in this study. Part II (13 items; range 0-52) assesses motor experiences of daily living and is completed by participants. Part III (33 scores from 18 items; range 0-132) assesses motor signs and is rated by the same qualified rater. Each item is scored 0-4 (0 = Normal, 4 = Severe). The combined possible score for Parts II and III is 184. The total score was calculated as (Sum of available item scores/Number of items with non-missing scores) × 13 for Part II and × 33 for Part III. Higher score indicates more severe symptoms of PD. Baseline was the value on Day 1. Change from Baseline (CFB) = Observed value - Baseline Value.

MDS-UPDRS was a comprehensive 50-question assessment that evaluated both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals and their caregivers, as well as sections that were consistently completed by the same clinician throughout the study. Part III assesses the motor signs of PD and is administered by the rater. It contains 33 scores based on 18 items. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. Maximum score for Part III was 132. Total score represented sum of the numerical response values for all items. The MDS-UPDRS Part III sum score was calculated as: (Sum of available item scores) / (Number of items with non-missing scores) × 33. Higher score indicates more severe symptoms of PD. Baseline was the value on Day 1. CFB = Observed value - Baseline Value.

The CGI-S was a 7-point scale used to assess the severity of illness, with response options ranging from 0 (not assessed), 1 (normal, not at all ill), 2 (borderline mentally ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), 7 (among the most extremely ill subjects). The CGI-S score represents the numerical rating assigned by the clinician, reflecting the participant's illness severity at the time of assessment, based on the clinician's prior experience with individuals with the same diagnosis. Higher scores reflected greater severity of illness. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

The PGI-S was a participant-completed assessment that rated PD severity on a scale of 1 to 5; 1 being none and 5 being very severe. The scores ranging from 1 (none), 2 (mild), 3 (moderate), 4 (severe) and 5 (very severe). Higher scores reflected greater illness severity. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

MDS-UPDRS was a comprehensive 50-question assessment that evaluated both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals and their caregivers, as well as sections that were consistently completed by the same clinician throughout the study. Part II assesses motor experiences of daily living (range 0-52). It contains 13 questions which are to be completed by the participant. It was a self-administered questionnaire completed by the participant, which was reviewed by the Investigator to ensure that all responses were properly completed. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The total score ranged from 0 to 52 and was calculated as (Sum of available item scores/Number of items with non-missing scores) × 13. A higher score indicates more severe symptoms of PD. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

The MDS-UPDRS was a comprehensive 50-question assessment that evaluated both motor and non-motor symptoms associated with PD. It included sections that were independently completed by individuals with PD and their caregivers, and by the same clinician throughout the study. Part I assessed non-motor aspects of experiences of daily living and consisted of 13 items, divided into two subparts. Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS UPDRS Part I sum score ranges from 0 to 52 and was calculated as (Sum of available item scores/Number of items with non-missing scores) × 13. A higher score indicated more severe symptoms of PD. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

The ESS is a participant self-administered questionnaire consisting of 8 questions. Respondents were asked to rate, on a 4-point scale (0 to 3: would never doze, slight chance of dozing, moderate chance of dozing, and high chance of dozing), their usual chances of dozing off or falling asleep while engaged in eight different activities, such as sitting and reading, watching television, or sitting in a public place. Most individuals engaged in these activities at least occasionally, though not necessarily on a daily basis. The ESS score was calculated as the sum of the 8 item scores, ranged from 0 to 24. Higher scores indicated a greater average sleep propensity in daily life or increased daytime sleepiness. The questionnaire typically takes not more than 2 to 3 minutes to complete. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

The NMSS is a 30-item rater-based instrument used to assess the frequency and severity of non-motor symptoms in participants across all stages of PD. The scale evaluates symptom burden across nine domains: cardiovascular (including falls), sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, urinary, sexual function, and miscellaneous. Responses were used to quantify symptoms based on two scales, severity (ranging from 0-3) and frequency (ranging from 0-4). The item score is calculated by multiplying frequency by severity. The total NMSS score is the sum of all 30 item scores (ranging from 0 to 360), with lower scores indicating fewer non-motor symptoms. The assessment is administered by a trained rater. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

Parts I, II, and III of the International Parkinson and MDS-UPDRS evaluates motor (Parts I and III) and non-motor (Part II) experiences and complications of PD by which it characterizes the extent and burden of disease. Questions/evaluations are divided across Part I (13 questions, 52 possible points), Part II (13 questions, 52 possible points), Part III (33 questions based on 18 items, several with right, left or other body distribution scores, 132 possible points) and summed. For each question, a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe for a total possible score of 236. A positive change in scores between Baseline to Week 12 indicates symptom/disease worsening. A negative change in score between Baseline to Week 12 indicates symptom/disease improvement. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

The PDSS-2 is a 15-item participant-reported outcome measure used to assess nocturnal disturbances in PD. It employed a 5-point frequency scale ranging from "very often" (0) to "never" (4). The total score ranged from 0 to 60, with higher scores indicating greater impairment. Baseline was the value on Day 1. CFB = Observed value - Baseline Value

An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical trial subject who had been administered a medicinal product, and which did not necessarily have to bear a causal relationship with the treatment. A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose. A serious adverse event (SAE) was any untoward medical occurrence during a clinical trial that resulted in significant harm or risk to a participant.

A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose. The severity of TEAEs is reported as indicated on the electronic case report form (eCRF) by the Investigator where mild indicates asymptomatic or mild symptoms; no intervention indicated; moderate: Minimal, local, or non-invasive intervention indicated; Severe: Medically significant but not immediately life-threatening.

A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose.

A comprehensive physical examination will be conducted by a qualified physician, encompassing measurements of body weight and height, assessment of general appearance, and evaluation of the head, ears, eyes, nose, throat, mouth, neck, heart, lungs, abdomen, musculoskeletal and neurological systems, extremities, and skin.

Vital signs included temperature, respiration rate, heart rate, and blood pressure, and were collected at the specified timepoints. Blood pressure was measured after participants had remained in a supine position for at least 5 minutes, and again within 1 to 3 minutes of standing.

Participants had chose to withdraw from (i.e., discontinue his or her participation in) an ongoing research study, or when an investigator terminated a participant's participation.

Twelve-lead ECGs were recorded using an ECG machine that automatically calculated the heart rate and measured the PR interval, RR interval, QRS interval, QT interval, and QTcF (QT Interval Corrected Using Fridericia's Formula) and QTcB intervals (QT interval corrected by Bazett's formula). ECG recordings were obtained with participants in a supine position following an approximately 10-minute period of rest.

Blood samples were collected for the assessment of alanine aminotransferase, albumin, alkaline phosphatase, aspartate aminotransferase, bilirubin, calcium, carbon dioxide, chloride, choriogonadotropin beta, creatine kinase, creatinine, direct bilirubin, gamma glutamyl transferase, glomerular filtration rate, glucose, lactate dehydrogenase, potassium, protein, sodium, urea nitrogen.

Blood samples were collected for the assessment of complete blood count (CBC) including hemoglobin, platelet count, and white blood cell counts, and differential to include the absolute counts for neutrophils, lymphocytes, eosinophils, and monocytes.

If a participant had used controlled prescription drugs and over-the-counter medications for purposes not prescribed or intended such as to get high, feel stimulated or sedated; taken more of the substance than prescribed or recommended; or taken the substance too often or for a longer period of time than was prescribed or recommended.

Included all participants who had completed the study treatment for 12 weeks and had the corresponding Week 12 efficacy assessment.

Suicidal ideation and behavior were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS), a validated tool for evaluating the presence and severity of suicide risk. The C-SSRS rates suicidal ideation on a 5-point scale, where 1 indicates a wish to be dead (passive ideation) and 5 represents active suicidal ideation with specific plan and intent (the highest severity). Higher scores reflect greater suicidal risk. In addition to ideation, the C-SSRS captures the presence or absence of suicidal behaviors, including actual attempts, interrupted or aborted attempts, and preparatory acts or behaviors. Suicidal behaviors are summarized categorically (Yes/No) and reported as the number and percentage of participants exhibiting each type.

An AE was defined as any untoward medical occurrence in a participant or clinical trial subject who had been administered a medicinal product, and which did not necessarily have to bear a causal relationship with the treatment. An AE could therefore have been any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease that was temporally associated with the use of a medicinal product, regardless of whether it was considered related to the product. A TEAE was an AE that began on or after administration of the first dose of the study drug or represented an increase in severity or frequency occurring on or after the first dose.