K0706 in people with dementia with Lewy bodies

A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of K0706 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics and Clinical Outcomes in Dementia With Lewy Bodies (DLB)

This trial will see if K0706 is safe, tolerable, and changes cerebrospinal fluid and blood biomarkers in people with dementia with Lewy bodies.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 25 Years to 90 Years
• Sex: All
• Sponsor: Georgetown University (Academic / other)
• Locations: 1 site (Washington D.C., District of Columbia)
• Trial ID: NCT03996460 on ClinicalTrials.gov

What this trial studies

This Phase 2, randomized, placebo-controlled trial will enroll 45 participants with clinically diagnosed dementia with Lewy bodies and randomize them 1:1:1 to low-dose K0706 (192 mg sachet), high-dose K0706 (384 mg sachet), or matching placebo for 12 weeks followed by a 4-week washout. The primary focus is safety and tolerability, with serial CSF and plasma biomarker measurements (including alpha-synuclein, tau, and amyloid species) to look for drug-related changes. Clinical measures of cognition, behavior, and motor function will be collected to explore symptomatic effects. The trial is conducted at MedStar Georgetown University Hospital under a sponsor collaboration with Sun Pharma Advanced Research Company.

Who should consider this trial

Good fit: Ideal candidates are medically stable adults aged 25–90 with a clinical diagnosis of dementia with Lewy bodies (per McKeith criteria), MoCA ≥14, defined parkinsonism (UPDRS criteria), and stable dopaminergic and cholinergic medications for the required lead-in periods.

Not a fit: People with advanced or unstable medical/psychiatric conditions, MoCA below enrollment cutoff, lack of parkinsonism, or those unable to travel to the study site are unlikely to qualify or benefit from this trial.

Why it matters

Potential benefit: If successful, K0706 could provide a well-tolerated treatment that alters disease-related biomarkers and might lead to symptomatic or disease-modifying benefits for people with DLB.

How similar studies have performed: Approaches targeting alpha-synuclein and related biomarkers are an active but early area of research with mixed results, and this specific oral K0706 intervention is novel and not yet proven in DLB.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent
2. Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR)
3. Age of 25-90 years, medically stable
4. Clinical diagnosis of DLB according to McKeith et al (https://www.ncbi.nlm.nih.gov/pubmed/28592453) with both dementia MoCA≥14 and Parkinsonian defined as bradykinesia in combination with rest tremor, rigidity or both UPDRS I-III ≤ 50 and UPDRS-III between 20-40.
5. Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
6. Stable on Levodopa no more than 800mg daily, acetylcholinesterase inhibitors, dopamine agonists for at least 6 weeks
7. Stable on monoamine oxidase inhibitors (MOA-B) for at least 4 weeks before enrollment and during the trial
8. Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
9. Corrected QT interval (QTc) 350-470 ms, inclusive
10. Participants must be willing to undergo Lumbar puncture (LP) at baseline and 3 months after treatment.

Exclusion Criteria:

1. Medical history of liver or pancreatic disease, GI ulcers and Chron's disease, kidney, GI, or blood problems
2. Abnormal liver function defined as Aspartate aminotransferase ( AST) and/or Alanine aminotransferase (ALT) \> 100% the upper limit of the normal
3. Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal or proteinuria
4. History of Human immunodeficiency virus (HIV), clinically significant chronic hepatitis, or other active infection
5. Hypokalemia, hypomagnesaemia, or long QT syndrome- QTc≥471 ms or concomitant drugs known to prolong the QTc interval and history of any cardiovascular disease, including myocardial infarction or cardiac failure, angina, arrhythmia
6. History or presence of significant cardiac conditions including: cardiovascular or cerebrovascular event (e.g. myocardial infarction, unstable angina, or stroke), congestive heart failure, first, second- or third-degree atrioventricular block, sick sinus syndrome, or other serious cardiac rhythm disturbances, any history of Torsade de Pointes.
7. Treatment with any of the following drugs at the time of screening or the preceding 30 days, and/or planned use over the course of the trial: Treatment with Class IA or III antiarrhythmic drugs (e.g. quinidine), treatment with QT prolonging drugs (www.crediblemeds.org)- excluding SSRIs (e.g. Citalopram, Escitalopram, Paroxetine, Sertraline, Duloxetine, Trazodone, etc.). Should treatment with any of these agents be required, therapy with K0706 should be interrupted.
8. Females must not be lactating, pregnant or with possible pregnancy
9. Clinical signs indicating syndromes other than DLB including, AD idiopathic PD, corticobasal degeneration, supranuclear gaze palsy, multiple system atrophy, chronic traumatic encephalopathy, signs of frontal dementia, history of stroke, head injury or encephalitis, cerebellar signs, early severe autonomic involvement, Babinski sign
10. Current evidence or history in past two years of epilepsy, focal brain lesion, head injury with loss of consciousness or Diagnostic and Statistical Manual of Mental Disorders 4th Edition ( DSM-IV) criteria for any active major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
11. Evidence of any significant clinical disorder or laboratory finding that renders the participant unsuitable for receiving an investigational drug including clinically significant or unstable hematologic, hepatic, cardiovascular, pulmonary, gastrointestinal, endocrine, metabolic, renal or other systemic disease or laboratory abnormality.
12. Active neoplastic disease, history of cancer five years prior to screening, including breast cancer (history of skin melanoma or stable prostate cancer are not exclusionary)
13. Contraindications to LP: prior lumbosacral spine surgery, severe degenerative joint disease or deformity of the spine, platelets \< 100,000, use of Coumadin/warfarin, or history of a bleeding disorder.
14. Must not be on any immunosuppressant medications
15. Must not be enrolled as an active participant in another clinical study.

Where this trial is running

Washington D.C., District of Columbia

• MedStar Georgetown University Hospital — Washington D.C., District of Columbia, United States (Recruiting)

Study contacts

• Principal investigator: Fernando L Pagan, MD — Georgetown University
• Study coordinator: Myrna Joy J Arellano, RN

Conditions Dementia With Lewy Bodies