K0706 for Patients Diagnosed With Dementia With Lewy Bodies

NCT03996460 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00000266
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and tolerability of treatment with K0706 in Dementia with Lewy Bodies (DLB). The hypothesis is that K0706 will be safe and tolerable and that this drug will alter CSF and plasma biomarkers in DLB. Clinical assessments of cognitive, behavioral and motor functioning will also be evaluated. A total of 45 participants will be randomized 1:1:1 into 3 groups (n=15/per group) to be treated with sachet of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) or sachet of 384 mg powder of K0706 (equivalent to 192 capsule of K0706) or sachet of matching placebo ( equivalent to a capsule of placebo) for 12 weeks, followed by 4-week wash-out period.

Conditions

Dementia With Lewy Bodies

Outcome Measures

Primary Outcomes (1)

• Evidence of treatment-emergent adverse effects (safety and tolerability)

  The investigators will determine safety and tolerability by using the occurrence of adverse events (AEs) of interest, including myelosuppression, urinary, pancreatic and hepatic disorders, gastrointestinal (GI), kidney disorders, Corrected QT-interval (QTc)prolongation as per SPARC Ltd Investigator Brochure (IB).

  12 weeks

Secondary Outcomes (4)

• Measurement of K0706 concentration in plasma

  12 weeks

• Measurement of K0706 concentration in CSF

  12 weeks

• Measurement of Biomarker concentration in plasma

  12 weeks

• Measurement of Biomarker concentration in CSF

  12 weeks

Other Outcomes (10)

• Measurement of the effects of K0706 on Cognition using the Montreal Cognitive Assessment (MoCA)

  12 weeks

• Measurement of the effects of K0706 on Cognition using the Trail Making Test (TMT)

  12 weeks

• Measuring the effects of K0706 on Cognition using the Alzheimer's Disease Assessment Scale - cognitive (ADAS-cog).

  12 weeks

Study Arms (3)

Placebo powder

PLACEBO COMPARATOR

Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1). Fifteen (15) patients in arm 1 (group 1) will receive the matching placebo powder orally once daily for 12 weeks (90 days).

Drug: Placebo

192 mg powder of K0706

ACTIVE COMPARATOR

Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1) .Fifteen (15) patients in arm 2 (group 2) will receive the 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) orally once daily for 12 weeks (90 days).

Drug: 192 mg powder of K0706

384 mg powder of K0706

ACTIVE COMPARATOR

Forty five (45) participants will be recruited and randomized into 3 arms (1:1:1) .Fifteen (15) patients in arm 3 (group 3) will receive the 384 mg powder of K0706 (equivalent to 192 mg capsule of K0706) orally once daily for 12 weeks(90 days).

Drug: 384 mg powder of K0706

Interventions

Placebo DRUG

Fifteen (15) patients in group 1 will receive the sachet of matching placebo ( equivalent to a capsule of placebo"sugar pill") orally daily for 12 weeks (90 days) without food.

Placebo powder

192 mg powder of K0706 DRUG

Fifteen (15) patients in group 2 will receive the sachet of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) orally for 12 weeks (90 days) without food.

192 mg powder of K0706

384 mg powder of K0706 DRUG

Fifteen (15) patients in group 3 will receive the 384 mg powder of K0706 (equivalent to 192 capsule of K0706) orally daily for 12 weeks (90 days) without food.

384 mg powder of K0706

Eligibility Criteria

• Age: 25 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Capable of providing informed consent and complying with study procedures. Subjects who are unable to provide consent may use a Legally Authorized Representative (LAR)
• Age of 25-90 years, medically stable
• 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.
• Dementia and Parkinsonism must be present with at least one other symptom such as fluctuation, visual hallucinations or REM sleep behavioral disorder (RBD)
• Stable on Levodopa no more than 800mg daily, acetylcholinesterase inhibitors, dopamine agonists for at least 6 weeks
• Stable on monoamine oxidase inhibitors (MOA-B) for at least 4 weeks before enrollment and during the trial
• Stable concomitant medical and/or psychiatric illnesses in the judgement of the PI
• Corrected QT interval (QTc) 350-470 ms, inclusive
• Participants must be willing to undergo Lumbar puncture (LP) at baseline and 3 months after treatment.

You may not qualify if:

• Medical history of liver or pancreatic disease, GI ulcers and Chron's disease, kidney, GI, or blood problems
• Abnormal liver function defined as Aspartate aminotransferase ( AST) and/or Alanine aminotransferase (ALT) \> 100% the upper limit of the normal
• Renal insufficiency as defined by a serum creatinine \> 1.5 times the upper limit of normal or proteinuria
• History of Human immunodeficiency virus (HIV), clinically significant chronic hepatitis, or other active infection
• 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
• 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.
• 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.
• Females must not be lactating, pregnant or with possible pregnancy
• 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
• 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
• 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.
• 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.
• Must not be on any immunosuppressant medications
• Must not be enrolled as an active participant in another clinical study.

Sponsors & Collaborators

• Georgetown University: lead
• Sun Pharma Advanced Research Company Limited: collaborator

Study Sites (1)

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Related Links

• https://sites.google.com/a/georgetown.edu/moussa-lab/home3

MeSH Terms

Conditions

Lewy Body Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Fernando L Pagan, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Myrna Joy J Arellano, RN

CONTACT

(202)-444-7273; mja6@gunet.georgetown.edu

Sara Matar, BS

CONTACT

202-687-7581; sm3469@georgetown.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomized by a Biostatistician by an internet based randomization module into three groups. The researchers include : Primary investigator , Sub-Investigators ,Clinical Coordinators, Nurse Practitioners, and Clinical Research unit (CRU) staff. The investigators will be blinded to the dosage. Medications for any patient will be labeled by the CRU with a package medical identification number (Med. Id). A patient specific patient identification number (Pat. Id.) will be assigned to each patient. The investigator will have to note the Pat.Id on the designated medication package number after randomization.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Of Neurology , Director of Movement Disorder Program, Medical Director of NPF COE at GUH , Fellowship Director

Model Details: The effects of 192 mg powder of K0706 ( equivalent to 96 mg capsule of K0706) versus 384 mg powder of K0706 (equivalent to 192 mg capsule of K0706) versus matching placebo powder taken daily by mouth for 12 weeks, followed by a 4 week wash-out period in individuals diagnosed with DLB will be evaluated.

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 24, 2019
• Study Start: September 5, 2019
• Primary Completion: June 1, 2023
• Study Completion: October 1, 2023
• Last Updated: October 19, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)