NCT05686044

A Dose-ranging Study to Investigate Efficacy of Buntanetap in Mild to Moderate AD

Completed Phase 2, PHASE3 Results posted Last updated 29 April 2025

What this trial tests

Phase 2, PHASE3 trial testing Buntanetap/Posiphen in Alzheimer Disease in 351 participants. Completed in 13 February 2024.

Timeline

1 April 2023

Primary endpoint
13 February 2024

13 February 2024

Quick facts

Lead sponsor	Annovis Bio Inc.
Phase	Phase 2, PHASE3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	351
Start date	1 April 2023
Primary completion	13 February 2024
Estimated completion	13 February 2024
Sites	54 locations across United States

Drugs / interventions tested

• Buntanetap/Posiphen — full drug profile →
• Placebo

Conditions studied

• Alzheimer Disease — all drugs for Alzheimer Disease →

Sponsor

Annovis Bio Inc. — full company profile →

Who can join

Adults 55 to 85, any sex, with Alzheimer Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline to Week 12 in ADAS-Cog11 Primary · Baseline to the end of treatment period (12 weeks)

Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog11) measures cognitive functions and non-cognitive functions such as mood and behavior. It was designed to measure the cognitive and behavioral domains known to be affected in Alzheimer disease, including memory, language, orientation, construction, and planning of simple designs, and completed simple goal-oriented behaviors. Specifically, the ADAS-Cog comprises ratings from 11 components: word recall, word recognition, constructional praxis, orientation, naming objects and fingers, commands, ideational praxis, remembering te

Group	Value	95% CI
Placebo	-2.32	± 0.533
7.5mg Buntanetap/Posiphen	-1.34	± 0.526
15mg Buntanetap/Posiphen	-3.01	± 0.534
30mg Buntanetap/Posiphen	-2.24	± 0.531

ADCS-CGIC at Week 12 Primary · Baseline to the end of treatment period (12 weeks)

Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of a trial. It relies on both direct examination of the patient and interview of informants. The ADCS-CGIC measures whether the effects of active treatment are substantial enough to be detected by a skilled and experienced clinician on the basis of a clinical interview and examination. It relies on both direct examination of the patient and an interview of the study partner.

Group	Value	95% CI
Placebo	3.58	± 0.129
7.5mg Buntanetap/Posiphen	3.96	± 0.128
15mg Buntanetap/Posiphen	3.61	± 0.131
30mg Buntanetap/Posiphen	3.83	± 0.132

Change From Baseline to Week 12 in ADCS-ADL Secondary · Baseline to end of treatment period (12 weeks)

Alzheimer's Disease Cooperative Study-Instrumental Activities of Daily Living Scale (ADCS-ADL) is a 23-item inventory scale developed as a rater-administered questionnaire answered by the participant's study partner. The ADCS-ADL measures 6 basic activities of daily living (BADL) items and 17 instrumental activities of daily living (IADL) items that provide a total score from 0-78, with a lower score indicating greater severity. Basic activities include basic self-care tasks such as feeding, mobility, toileting, bathing, grooming and dressing. Instrumental activities are more complex and vary

Group	Value	95% CI
Placebo	2.03	± 0.811
7.5mg Buntanetap/Posiphen	-0.14	± 0.806
15mg Buntanetap/Posiphen	1.71	± 0.831
30mg Buntanetap/Posiphen	0.15	± 0.822

Change From Baseline to Week 12 in Plasma Biomarkers Secondary · Baseline to the end of treatment period (12 weeks)

Plasma biomarkers measured: Glial fibrillary acidic protein (GFAP), Neurofilament light (NFL), TAR DNA-binding protein 43 (TDP43)

GFAP

Group	Value	95% CI
Placebo	5.5	± 74.32
30mg Buntanetap/Posiphen	2.1	± 69.44

NFL

Group	Value	95% CI
Placebo	0.4	± 6.88
30mg Buntanetap/Posiphen	-2.5	± 14.05

TDP43

Group	Value	95% CI
Placebo	-467.5	± 1474
30mg Buntanetap/Posiphen	-985.1	± 4950

Change From Baseline to Week 12 in ADAS-Cog11 for Biomarker Positive Participants With Baseline MMSE Scores 21-24 Secondary · Baseline to the end of treatment period (12 weeks)

Change in the ADAS-Cog11 score from Baseline to the End of Trial. Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) measures cognitive functions and non-cognitive functions such as mood and behavior. It was designed to measure the cognitive and behavioral domains known to be affected in Alzheimer disease, including memory, language, orientation, construction, and planning of simple designs, and completed simple goal-oriented behaviors. Specifically, the ADAS-Cog comprises ratings from 11 components: word recall, word recognition, constructional praxis, orientation, nami

Group	Value	95% CI
Placebo	-0.26	± 0.911
7.5mg Buntanetap/Posiphen	-2.19	± 0.865
15mg Buntanetap/Posiphen	-2.79	± 0.815
30mg Buntanetap/Posiphen	-3.32	± 0.820

Adverse events — posted to ClinicalTrials.gov

Time frame: From consent to end of trial (up to 5 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 3/88 (3%)

Deaths: 0/88

7.5mg Buntanetap/Posiphen

Serious: 0/86 (0%)

Deaths: 0/86

15mg Buntanetap/Posiphen

Serious: 0/85 (0%)

Deaths: 0/85

30mg Buntanetap/Posiphen

Serious: 3/87 (3%)

Deaths: 0/87

Serious adverse events (9 terms)

Reaction	System	Placebo	7.5mg Buntanetap/Posiphen	15mg Buntanetap/Posiphen	30mg Buntanetap/Posiphen
Pneumonia	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—
Soft tissue mass	Musculoskeletal and connective tissue disorders	—	—	—	—
Cardiac failure congestive	Cardiac disorders	—	—	—	—
Oesophagitis	Gastrointestinal disorders	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Placebo	7.5mg Buntanetap/Posiphen	15mg Buntanetap/Posiphen	30mg Buntanetap/Posiphen
Dizziness	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Pneumonia, Urinary tract infection, Osteoarthritis, Soft tissue mass, Cardiac failure congestive, Oesophagitis, Dehydration, Acute respiratory failure.

Data from ClinicalTrials.gov NCT05686044 adverse events section.

Sponsor's own description

The purpose of this study is to measure efficacy and safety of three different doses of buntanetap/Posiphen compared with placebo in participants with mild to moderate Alzheimer's disease.

Study details include:

The double-blind treatment duration will include a screening period of up to 42 days followed by 12 weeks of treatment at home.

The study duration will be 4-5 months. There will be 4 in-clinic visits and 1 phone call.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.