¶ MLC 901 (NeuroAid II) — ATHENE II (NCT07191028)
¶ Overview
MLC 901 (NeuroAid™ II) is a neuroprotective and neurotrophic compound in Phase 3 clinical development for the treatment of Alzheimer's disease (AD). The ATHENE II trial (NCT07191028) is a multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MLC901 in patients with mild to moderate Alzheimer's disease[@clinical_trial].
MLC901 (NeuroAid II) is a fixed-dose combination of nine standardized herbal extracts derived from traditional Chinese medicine, designed to promote neuroprotection, support neuronal survival, and enhance synaptic function. The compound has been previously studied in stroke recovery and cognitive disorders, with prior clinical evidence suggesting benefits for memory and cognitive function in AD patients[@neuroaid_mechanism][@neuroaid_ad_prior].
Trial Identifier: NCT07191028
Trial Name: ATHENE II
Status: Not Yet Recruiting (as of March 2026)
Phase: Phase 3
Enrollment: 350 participants
Sponsor: Moleac Pte Ltd[@moleac_sponsor]
Collaborator: National University Hospital, Singapore
Principal Investigator: Christopher Li Hsian Chen
Start Date (Estimated): December 2025
Completion Date (Estimated): June 2028
¶ Mechanism of Action
MLC901 (NeuroAid II) is a multi-component neuroprotective agent derived from traditional Chinese medicine formulations. The exact mechanism involves multiple pathways:
¶ Neuroprotective Effects
- Anti-excitotoxic activity: Modulates glutamate toxicity and reduces excitotoxic neuronal damage
- Antioxidant properties: Reduces oxidative stress in neuronal tissues
- Anti-inflammatory effects: Inhibits neuroinflammatory pathways implicated in AD progression
- Mitochondrial protection: Supports mitochondrial function and cellular energy metabolism
- Synaptic plasticity enhancement: Promotes synaptic remodeling and neuronal connectivity
¶ Cognitive Enhancement Mechanisms
The compound is designed to[@cognition_composite]:
- Enhance cholinergic neurotransmission
- Support neurotrophic factor signaling (e.g., BDNF)
- Protect against amyloid-beta induced neurotoxicity
- Reduce tau phosphorylation abnormalities
- Modulate neuroinflammation
¶ Distinguishing Features
- Multi-target approach: unlike single-target AD therapies, MLC901 acts through multiple pathways
- Oral administration: convenient dosing regimen (2 capsules, 3 times daily)
- Good tolerability: historical safety profile from prior studies in stroke and AD
- Adjunctive potential: may be combined with standard AD therapies (AChEIs, memantine)
¶ Trial Design
¶ Study Structure
| Parameter | Value |
|---|---|
| Design | Multicenter, randomized, double-blind, placebo-controlled |
| Phase | Phase 3 |
| Allocation | Randomized (1:1) |
| Masking | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Duration | 12 months treatment |
| Follow-up | Up to 52 weeks |
¶ Treatment Arms
| Arm | Intervention | Dosage | Duration |
|---|---|---|---|
| Treatment | MLC 901 (NeuroAid II) | Oral capsule, 2 capsules 3 times daily | 12 months |
| Placebo | Placebo | Oral capsule, 2 capsules 3 times daily | 12 months |
¶ Study Population
| Parameter | Criteria |
|---|---|
| Diagnosis | Alzheimer's disease (NIA-AA criteria) with elevated plasma p-tau217 |
| Age | ≥50 years |
| MMSE | 10-26 (mild to moderate AD) |
| Disease severity | Mild to moderate AD |
| Prior therapy | Stable AChEIs and/or memantine for ≥2 months (if applicable) |
| Caregiver | Designated study partner with ≥8 hours/week contact |
¶ Primary Endpoints
¶ Cognitive Function (ADAS-Cog14)
The primary endpoint is the change from baseline in ADAS-Cog14 (Alzheimer's Disease Assessment Scale-Cognitive Subscale-14) scores at 12 months[@cognition_composite].
- Scale: 0-90 (higher scores indicate greater impairment)
- Timepoints: Baseline, Month 3, Month 6, Month 9, Month 12
- Expected outcome: Statistical improvement in MLC901 arm vs. placebo
¶ Secondary Endpoints
¶ Clinical Outcomes
| Endpoint | Measure | Timepoints |
|---|---|---|
| CDR | Global Score and Sum of Boxes | Baseline, Month 6, Month 12 |
| MMSE | Global cognitive function (0-30) | Baseline, Month 3, Month 6, Month 9, Month 12 |
| MoCA | Cognitive function (0-30) | Baseline, Month 6, Month 12 |
| ADCS-ADL | Activities of Daily Living (0-78) | Baseline, Month 6, Month 12 |
| NPI | Neuropsychiatric Inventory | Baseline, Month 12 |
¶ Biomarker Outcomes
| Biomarker | Description |
|---|---|
| Plasma p-tau217 | Phosphorylated tau at threonine 217 |
| Plasma NfL | Neurofilament Light Chain |
| Plasma GFAP | Glial Fibrillary Acidic Protein |
¶ Safety Endpoints
- Adverse events monitoring throughout 52-week treatment period
- Vital signs, laboratory parameters, and ECG monitoring
¶ Eligibility Criteria
¶ Inclusion Criteria
- Age ≥50 years
- Diagnosis of Alzheimer's disease based on NIA-AA criteria
- Confirmed elevated plasma p-tau217 (biomarker evidence)
- MMSE score between 10 and 26 (mild to moderate AD)
- Stable AD treatment (AChEIs, memantine) for ≥2 months prior to screening (if applicable)
- Designated study partner with ≥8 hours/week contact
- Adequate literacy, vision, and hearing for cognitive assessments
¶ Exclusion Criteria
- Neurological disorders other than AD (e.g., Parkinson's disease, Dementia with Lewy bodies)
- Clinically significant cerebrovascular disease
- Serious or unstable medical illnesses
- CDR Global Score of 0 (no impairment), 0.5 (questionable), or 3 (severe dementia)
- Severe visual or hearing impairment
- Serum creatinine >130 µmol/L
- Pregnancy or breastfeeding
- Participation in other clinical trials within 60 days
- Current use of disease-modifying AD therapies or neuroprotective agents (e.g., Ginkgo biloba, Neurotain)
- Known hypersensitivity to MLC901 components
¶ Rationale
¶ Unmet Need in AD Treatment
Current FDA-approved AD therapies provide only symptomatic benefits and do not address the underlying neuropathology. MLC901 represents a neuroprotective approach that[@neuroaid_mechanism][@neuroaid_ad_prior]:
- Targets multiple pathogenic pathways — addressing excitotoxicity, oxidative stress, and neuroinflammation
- Promotes neuronal survival — enhances neurotrophic support and synaptic plasticity
- Potential disease modification — may slow disease progression beyond symptomatic effects
- Complementary to existing therapies — may be combined with AChEIs and memantine
¶ Prior Clinical Evidence
Previous studies with NeuroAid (MLC901) have demonstrated:
- Improved neurological recovery in stroke patients (neurorestorative effects)
- Cognitive benefits in observational AD studies
- Good safety and tolerability profile
- No significant drug-drug interactions with standard AD medications
¶ Biomarker-Driven Enrollment
The ATHENE II trial uses plasma p-tau217 for patient selection, ensuring enrollment of patients with AD-specific pathology and potentially improving trial sensitivity to detect treatment effects[@cognition_composite].
¶ Current Status
This trial is not yet recruiting as of March 2026. Recruitment is expected to begin in December 2025 at National University Hospital, Singapore.
For updated information, refer to ClinicalTrials.gov.
¶ Related Pages
- MLC 901 (NeuroAid) — Stroke Recovery
- Alzheimer's Disease Clinical Trials Overview
- Neuroprotective Therapies in Development
- Alzheimer's Disease
- Promising Clinical Trials in Neurodegeneration
- ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living)
- ADAS-Cog (Alzheimer's Disease Assessment Scale)
¶ Gallery
¶ References
- MLC 901 (NeuroAid II) - ATHENE II - NCT07191028 (2026)
- Moleac Pte Ltd - NeuroAid (2025)
- Clinch et al., NeuroAiD (MLC901) enhances neurological recovery after stroke (2022)
- Pons et al., NeuroAiD (MLC901) in Alzheimer's disease: a prospective observational study (2023)
- Kavirajan et al., Cognitive composite endpoints in Alzheimer's disease clinical trials (2024)