A Study to Evaluate the Safety, Tolerability, and Efficacy of TML-6 in Participants With Early Alzheimer's Disease

NCT07612150 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: MLB_TML-6_AD_P2-012026-525539-18-00
• Study Type: interventional
• Target: 210
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary purpose of the study is to assess if treatment with TML-6 for 52 weeks will be effective in slowing, stopping, or improving cognitive and functional decline in participants with early Alzheimer's Disease (AD) as compared to participants receiving placebo.

Conditions

Alzheimer Disease

Keywords

Multicenter; Alzheimer's Disease Assessment Scale-Cognitive Subscale; Early Alzheimer's Disease; Mild Cognitive Impairment due to Alzheimer's Disease; Mild Alzheimer's Disease Dementia; Clinical Dementia Rating-Sum of Boxes; Integrated Alzheimer's Disease Rating Scale; Blood Biomarkers; p-Tau217; Autolysosomal Pathway; TML-6

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Clinical Dementia Rating -Sum of Boxes (CDR-SB) Score at Week 52

  The CDR-SB is a clinician-rated outcome derived from a semi-structured interview with the participant and study partner. It assesses cognitive and functional impairment across six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Domain severity scores are summed to generate the CDR-SB, with higher scores indicating greater disease severity.

  Baseline and at Week 52

Secondary Outcomes (9)

• Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score at Week 52

  Baseline and at Week 52

• Change From Baseline to Week 52 in Blood Biomarker- Blood p-Tau217

  Baseline and at Week 52

• Change From Baseline to Week 52 in Blood Biomarker- Amyloid β-Protein Aβ40 and Amyloid β-Protein Aβ42

  Baseline and at Week 52

• Number of Participants With Spontaneously Reported Adverse Events (AEs)

  From first dose of study drug up to end of follow up (up to Week 65)

• Number of Participants With Clinically Significant Changes in Laboratory Test Results

  From first dose of study drug up to end of follow up (up to Week 65)

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Participants will TML-6 matching placebo tablets, orally, once daily for up to Week 52.

Other: Placebo

TML-6 100 mg

EXPERIMENTAL

Participants will receive TML-6 100 milligram (mg), tablet, orally, once daily for up to Week 52.

Drug: TML-6

TML-6 200 mg

EXPERIMENTAL

Participants will receive TML-6 200 mg, tablet, orally, once daily for up to Week 52.

Drug: TML-6

Interventions

TML-6 DRUG

TML-6 tablets for oral administration.

TML-6 100 mg; TML-6 200 mg

Placebo OTHER

TML-6 matching placebo tablets for oral administration.

Placebo

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male participants or post-menopausal female participants (defined as women who have not had a menstrual period for at least 12 consecutive months, without the influence of medications known to cause amenorrhea) aged 60 to 85 years (inclusive) at the time of informed consent. If the male participant is sexually active with a female partner of childbearing potential, he must be willing and able to comply with the protocol-specified contraception and reproductive risk management requirements and agree to refrain from sperm donation, in accordance with the protocol.
• Screening of blood biomarkers: local p-Tau217 or p-Tau181 should meet the National Institute of Aging - Alzheimer's Association (NIA-AA) core clinical criteria, Revised Criteria for Diagnosis and Staging of Alzheimer's Disease, 2024 Updated.
• Have a clinical diagnosis of Mild Cognitive Impairment (MCI) due to AD - intermediate likelihood (Alzheimer's Association International Conference \[AAIC\] Stage 2 to 3):
• Meet the NIA-AA core clinical criteria for MCI due to AD.
• Blood biomarkers cut-off value (any one of the following):
• Simoa® ALZpath p-Tau217: high cut-off value greater than or equal (\>=) 0.551 picograms per milliliter (pg/mL)
• Fujirebio Lumipulse® p-Tau217: high cut-off value \>=0.34 pg/mL
• C2N Diagnostics PrecivityAD2™ blood test: percentage (%) p-Tau217 cut point \>=4.2%
• Roche Elecsys® p-Tau181: high cut-off value \>=0.934 pg/mL
• Mini-Mental State Examination (MMSE) score of 24 to 28 (inclusive) at screening.
• CDR-Global Score of 0.5 at screening. OR
• Have a clinical diagnosis of mild AD dementia (Alzheimer's Association International Conference Alzheimer's Disease \[AAIC AD\] staging 4):
• Meet the NIA-AA core clinical criteria for probable AD dementia.
• Blood biomarkers cut-off value (any one of the following):
• Simoa® ALZpath p-Tau217: high cut-off value \>=0.551 pg/mL

You may not qualify if:

• Female participants who are not yet menopausal or have not reached 1-year post-menopause are excluded.
• Any participant who has received anti-amyloid therapy.
• Any laboratory values with the following deviations at screening and admission. The laboratory test may be repeated once during the screening period.
• Alanine aminotransferase (ALT) greater than (\>) upper limit of normal (ULN)
• Aspartate aminotransferase (AST) \>ULN
• Total bilirubin (TBL) \>ULN of the reference range
• \* If predefined agreement is established in this protocol and, in the opinion of the investigator, the findings are clinically non-significant, exceptions may be made for
• Isolated ALT and/or AST elevation less than (\<) 1.5\*ULN.
• Bilirubin values that are above the ULN when the participant has an underlying diagnosis of Gilbert's syndrome.
• Such cases should be documented in the participant's source records and may be reviewed by the Sponsor during routine monitoring.
• Absolute neutrophil count \<1500 unless if it can be demonstrated that this is the participant's normal values.
• Hemoglobin \<12 grams per deciliter (g/dL)
• Estimated glomerular filtration rate of \<50 milliliters per minute per 1.73 square meters (mL/min/1.73m\^2) (calculated by either the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] or Modification of Diet in Renal Disease \[MDRD\] by the method used at an International Organization for Standardization or Taiwan Accreditation Foundation-accredited hospital is accepted).
• Total cholesterol \>=240 milligrams per deciliter (mg/dL)
• Participants who have been tested positive for the following tests:

Sponsors & Collaborators

• Merry Life Biomedical Co., Ltd.: lead

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Chia-Yu Hsu, PhD

CONTACT

+886-6-2531571; rd03@tmlbio.com

Chien-Hong Lin, PhD

CONTACT

+886-6-2531571; chien-hong.lin@tmlbio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2026
• First Posted: May 28, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share