Alzheimer's Disease THErapy With NEuroaid II

NCT07191028 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: EFSA2025_01
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

Brief Summary

ATHENE II is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial designed to evaluate the efficacy and safety of MLC901 in subjects with mild to moderate Alzheimer's disease, as well as its effects on plasma biomarkers compared to placebo.

Conditions

Alzheimer's Disease Dementia

Keywords

MLC901; NeuroAiD™II; Alzheimer's disease; multicenter; randomised; double blind; placebo controlled

Outcome Measures

Primary Outcomes (1)

• Alzheimer's Disease Assessment Scale-Cognitive Subscale14 (ADAS-Cog14)

  The ADAS-Cog is a rater-administered instrument designed to assess the severity of cognitive impairment and associated non-cognitive behaviors characteristic of individuals with AD. It is the most widely used cognitive scale in clinical trials evaluating treatments for mild to moderate AD. For this study, the version of ADAS-Cog14 will be used as the primary efficacy assessment. The ADAS-Cog14 consists of 14 items assessing key areas of cognitive function that are commonly impaired in AD, including: orientation, word recall, word recognition, remembering word recognition test instructions, commands, comprehension of spoken language, naming, word-finding difficulty, spoken language ability, construction praxis, ideational praxis, delayed word recall, number cancellation and maze completion measures. The ADAS-Cog14 total score ranges from 0 to 90, with higher scores indicating greater cognitive impairment.

  Baseline, Month 3, Month 6, Month 9 and Month 12

Secondary Outcomes (6)

• Clinical Dementia Rating (CDR): Global Score and Sum of Boxes (CDR-SB)

  Baseline, Month 6 and Month 12

• Mini-Mental State Examination (MMSE)

  Baseline, Month 3, Month 6, Month 9 and Month 12

• Montreal Cognitive Assessment (MoCA)

  Baseline, Month 3, Month 6, Month 9 and Month 12

• Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL)

  Baseline, Month 6 and Month 12

• Neuropsychiatric Inventory (NPI)

  Baseline, Month 6 and Month 12

Other Outcomes (3)

• Plasma biomarkers - phosphorylated tau (p-tau217)

  Baseline, Month 6 and Month 12

• Plasma biomarkers - neurofilament light chain (NfL)

  Baseline, Month 6 and Month 12

• Plasma biomarkers - glial fibrillary acidic protein (GFAP)

  Baseline, Month 6 and Month 12

Study Arms (2)

MLC901

EXPERIMENTAL

Active arm

Drug: MLC 901

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

MLC 901 DRUG

Oral capsule, 2 capsules 3 times a day for 12 months

MLC901

Placebo DRUG

Oral capsule, 2 capsules 3 times a day for 12 months

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged ≥ 50 years at the time of providing informed consent.
• Diagnosis of AD based on the National Institute on Ageing and the Alzheimer's Association criteria, supported by the presence of a Core 1 AD biomarker, specifically elevated plasma ptau217.
• MMSE score between 10 and 26, inclusive, at baseline, corresponding to mild to moderate AD.
• Subjects may be either treatment-naïve or currently receiving stable symptomatic treatment for AD for at least the 2 months prior to screening, including AChEIs, memantine, or a combination of both.
• Subjects must have a designated study partner who provides ongoing support during the study and interacts with the subject for a minimum of 8 hours per week, and will accompany the subject to study visits or be available by telephone at designated times. A second study partner may serve as backup. If the original study partner withdraws from participation, a replacement study partner may be permitted at the investigator's discretion. The replacement study partner must provide informed consent prior to their first study visit with the subject.
• Both the subject (or their legally authorized representative) and the study partner(s) must be capable of providing informed consent.
• Subjects must have adequate literacy, vision, and hearing, in the opinion of the investigator at the time of screening, to allow for valid administration of the clinical outcome assessments.

You may not qualify if:

• Presence of any neurological disorder contributing to cognitive impairment other than AD, including but not limited to: Parkinson's disease, Dementia with Lewy bodies, and epilepsy or recurrent seizures.
• Evidence of other clinically significant cerebrovascular disease or intracranial abnormalities based on the latest brain CT or MRI, including but not limited to: multiple lacunar infarcts, large territorial infarcts, severe small vessel or white matter disease, normal pressure hydrocephalus, space occupying lesions.
• The most recent available scan (obtained at diagnosis or subsequently) is usually sufficient for screening eligibility to exclude these other conditions. Repeat imaging may need in some cases to be considered if there is clinically significant deterioration or new neurological signs suggestive of a cerebrovascular event.
• Presence of any serious or unstable medical illnesses, including but not limited to: cardiovascular, respiratory, gastroenterological, endocrinologic, immunologic, hematologic, hepatic, or renal and other conditions, that, in the investigator's judgment, may interfere with study participation or compromise subject safety.
• Patients with a CDR Global Score of 0, 0.5 or 3 at the Screening Phase, corresponding to no, very mild or severe dementia, respectively, will be excluded from the study.
• Severe visual or hearing impairment that would prevent the subject from accurately completing clinical outcome assessments.
• Serum creatinine \> 130 µmol/L at baseline, which may affect plasma biomarker analysis.
• Female subjects who are pregnant at screening.
• Participation in another clinical trial or receipt of any investigational product within 60 days or 5 half-lives (whichever is longer) prior to screening.
• Current use at baseline of any AD disease-modifying therapies or neuroprotective/nootropic agents, including Ginkgo biloba, Neurotain, Citicoline, Cerebrolysin, or Piracetam.
• Known hypersensitivity or allergic reaction to MLC901 or any of its components. Any known food allergy or hypersensitivity to Astragalus membranaceus, Ligusticum chuanxiong, Polygala tenuifolia, Angelica sinensis or members of the Fabaceae/Leguminosae family (e.g., legume, pea, bean), Polygalaceae family (e.g., milkwort, snakeroot), Apiaceae/Umbelliferae family (e.g., anise, caraway, carrot, celery, dill, parsley, parsnip) or Quillaja bark (soapbark).

Sponsors & Collaborators

• Moleac Pte Ltd.: lead
• National University Hospital, Singapore: collaborator

Study Sites (1)

National University Hospital Singapore

Singapore, Singapore

Location

Related Publications (5)

• Dib M, Ampil E, Kee HF, et al. A review of NeuroAiD™ II (MLC901) development in Alzheimer's disease treatment: promises of a multimodal pathway. J Neurol Res Rev Rep. 2022 Jun 30;1-13.

  BACKGROUND

• Lee WT, Hsian CCL, Lim YA. The effects of MLC901 on tau phosphorylation. Neuroreport. 2017 Nov 8;28(16):1043-1048. doi: 10.1097/WNR.0000000000000884.

  PMID: 28902708 BACKGROUND

• Lim YA, Murray LA, Lai MK, Chen C. NeuroAiD(R) (MLC601) and amyloid precursor protein processing. Cerebrovasc Dis. 2013;35 Suppl 1:30-7. doi: 10.1159/000346236. Epub 2013 Mar 14.

  PMID: 23548917 BACKGROUND

• Heurteaux C, Widmann C, Moha ou Maati H, Quintard H, Gandin C, Borsotto M, Veyssiere J, Onteniente B, Lazdunski M. NeuroAiD: properties for neuroprotection and neurorepair. Cerebrovasc Dis. 2013;35 Suppl 1:1-7. doi: 10.1159/000346228. Epub 2013 Mar 14.

  PMID: 23548913 BACKGROUND

• Heurteaux C, Gandin C, Borsotto M, Widmann C, Brau F, Lhuillier M, Onteniente B, Lazdunski M. Neuroprotective and neuroproliferative activities of NeuroAid (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology. 2010 Jun;58(7):987-1001. doi: 10.1016/j.neuropharm.2010.01.001. Epub 2010 Jan 11.

  PMID: 20064536 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Neuroaid

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Christopher Li Hsian Chen

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mei Fen Sung

CONTACT

+65 62113710; mea.sung@moleac.com

Peak Yuen Lee

CONTACT

+65 62113710; peakyuen.lee@moleac.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study partner and sponsor
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled, parellel-group study

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 24, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)