Safety and Efficacy of AR1005 in Patients with Lewy Body Disease (AR1005)

A Randomized, Double-blind, Phase IIa Clinical Trial to Study the Safety and Efficacy of AR1005 in Patients with Lewy Body Disease

This study is a phase 2a, single-center, double-blind and randomized clinical trial that evaluates the safety and efficacy of AR1005 administration in 60 patients with cognitive impairment due to Lewy body disease. The study evaluates whether the administration of AR1005 in patients with cognitive impairment due to Lewy body disease has the effect of improving cognitive function, behavioral psychological symptoms, cognitive fluctuations, movement, brain waves and brain activity.

Study Overview

• Status: Recruiting
• Conditions: Lewy Body Dementia
• Intervention / Treatment: Drug: AR1005; Drug: Rivastigmine 3 mg; Drug: Placebo

Detailed Description

60 patients will be randomized into either active or placebo groups (1:1). Both groups will concurrently receive standard treatment with rivastigmine for 20 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jung Lim Lee; Phone Number: +82-2-2227-7716; Email: jll2024@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Jung Lim Lee

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• men and women over the age of 60

  • Communication in Korean is possible and the purpose and process of the study are fully understood and agreed

    • Total score of 26 points or less in the simplified mental health assessment (K-MMSE)

      • Dementia Clinical Evaluation Scale (CDR) Total score of 0.5 or higher

        • Medical history, neurological examination, hematologic examination, Seoul neuropsychological examination 2nd edition, brain magnetic resonance imaging suspected of cognitive impairment due to dementia with Lewy bodies as the cause of cognitive decline

          i. Lewy body dementia

          1. In accordance with the guidelines for the 4th report of the Dementia with Lewy Bodies Consortium (DLBC) published in 2017, if it falls under Probable Dementia with Lewy Bodies

          2. Required Requirements

             1. Dementia, defined as cognitive decline that progresses sufficiently to impair normal social and professional functions or daily life
             2. Defects in attention, enforcement, and space-time capabilities are noticeable in the inspection

          3. Core clinical features

             1. variation in cognitive function
             2. vision
             3. Parkinson's syndrome: One or more manifestations of sinusitis, stable progress, or stiffness
             4. REM sleep behavior disorder

          4. Indicative biomarker

             1. Decreased intake of dopamine carrier PET-phase nuclear
             2. [I-123]-MIBG myocardial scintigraphy intake decreased
             3. REM sleep behavior disorder according to polymorphic test

          5. In the case of two or more key aspects, or one or more key clinical features and one or more indicative biomarkers are satisfied

             ii. Bulb Lewy body dementia (Prodromal DLB)

          1. If it falls under the Probable MCI-LB with a mild cognitive impairment according to the criteria for diagnosing precursor Lewy body dementia announced in 2020

          2. Required Requirements

             a. cognitive decline observed when judged by the patient, guardian, or clinician b. Objective cognitive decline (although it is not related to any cognitive domain, it should be mainly related to the deterioration of execution function and space-time ability)

          3. Core clinical features

             1. variation in cognitive function
             2. vision (nap, dazed, same document, angry)
             3. Parkinson's syndrome: One or more manifestations of sinusitis, stable progress, or stiffness
             4. REM sleep behavior disorder

          4. Indicative biomarker

             a. Decreased intake of dopamine carrier PET-phase nuclear b. [I-123]-MIBG myocardial scintigraphy intake decreased c. REM sleep behavior disorder according to polymorphic test

          5. The leading mild cognitive impairment due to dementia with Lewy bodies has two or more key features or satisfies one or more key clinical features and one or more indicative biomarkers

             ⑥ Patients with caregivers who are in regular contact with the subject (Note: caregivers may support the subject during the clinical trial [compliance supervision and reporting of the subject's status], defined as those who spend at least 8 hours per week with the subject)

             ⑦ Patients who can walk or move with walking aids (i.e., walkers, canes, or wheelchairs)

             ⑧ Patients with sufficient vision, hearing, language skills, motor skills, and comprehension to follow the examination procedure as judged by the tester (Aids such as glasses and hearing aids are allowed)

             ⑨ an examination Patients who have voluntarily decided to participate in this clinical trial and obtained the consent of the subject in writing from both the subject and the subject's legal representative (where written consent is not available, the tester shall keep a record of the matters that the subject has verbally agreed to participate in the trial)

             Exclusion Criteria:

• In hematologic and brain magnetic resonance imaging tests conducted within 6 months, other causes of cognitive decline such as neurosyphilis, hypo/hyper-throidism, metabolic encephalopathy, brain tumor, acute cerebral hemorrhage, acute cerebral infraction, and Wernicke's encephalopathy are suspected

  • Subjects who are or are suspected of having an irritable allergy to AR1005-KRP2-01

    • If you are already on antistatic medication

      • A person who cannot perform a brain magnetic resonance image (but if there is a brain magnetic resonance image taken within one year, the brain magnetic resonance image can be omitted)

        • voluntary Employees directly involved in this clinical study or their immediate family members who find it difficult to participate

          • If there is a history of psychiatric disorders: major effective disorder, schizophrenia, schizo-effective disorder

            ⑦ If an electroencephalogram cannot be performed

            ⑧ Patients who are already taking acetylcholinesterase inhibitor (donepezil and rivastigmine) or taking it in patch form (but can change to rivastigmine PO to participate in the study)

            ⑨ Patients with moderate to severe liver disorder (Child-Pugh grade B) and dialysis due to decreased renal functiona patient with end-stage renal impairment receiving

            ⑩ Patients discontinued administration due to aseptic meningitis associated with AR1005-KRP2-01

            ⑪ Patients with genetic problems such as galactose intolerance, lactose-degrading enzyme deficiency, or glucose-galactose absorption disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; AR1005 50 mg BID will be administered with rivastigmine 3 mg BID for 20 weeks.	Drug: AR1005; AR1005 inhibits sodium currents by selective binding to the inactive sodium channel, suppressing the release of the excitatory amino acid, glutamate.; Other Names: Scheduled for future release; Drug: Rivastigmine 3 mg; 3mg Rivastigmine will be administered BID for both active and placebo groups
Placebo Comparator: Placebo; Placebo BID will be administered with rivastigmine 3 mg BID for 20 weeks.	Drug: Rivastigmine 3 mg; 3mg Rivastigmine will be administered BID for both active and placebo groups; Drug: Placebo; Matching placebo for AR1005 to be administered BID for 20 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Dementia Rating-Sum Of Boxes (CDR-SOB) at Week 20	The CDR-SOB score ranges from 0 to 18, with 0 indicating no dementia symptoms and 18 indicating severe dementia. Higher scores on the CDR-SOB reflect a worse outcome, as they indicate more severe dementia symptoms.	20 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in K-MMSE over 20 weeks	Change in Korean-Mini Mental State Examination (K-MMSE) over 20 weeks	20 Weeks

Collaborators and Investigators

• Sponsor: Yonsei University
• Collaborators: AriBio Co., Ltd.; Samjin Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Byoung Seok Ye, MD, PhD, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 31, 2024
• First Submitted That Met QC Criteria: July 31, 2024
• First Posted (Actual): August 5, 2024

Study Record Updates

• Last Update Posted (Actual): October 2, 2024
• Last Update Submitted That Met QC Criteria: September 30, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Lewy body dementia; DLB
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Lewy Body Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Rivastigmine
• Other Study ID Numbers: AR1005-KRP2-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Will be made available after the study is completed.
• IPD Sharing Access Criteria: Access will be provided to qualified researchers affiliated with recognized institutions, who have a valid research plan and appropriate ethical approvals.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No