Safety, Tolerability and Biomarker-based Efficacy of NPI-001 (AT-001) in Subjects with Alzheimer’s Disease (AD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arctic Therapeutics ehf.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

3 Oct 2025 → ongoing

Decision date (initial)

2025-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519497-39-00

WHO UTN

U1111-1316-3118

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess safety and tolerability in response to NPI-001 (AT-001) administered orally in patients with Alzheimer’s disease (AD).• MRI imaging to assess ARIA H and ARIA E in the brain

Secondary objectives 6

1. • To assess biomarker-based efficacy in response to NPI-001 administered orally in patients with Alzheimer’s disease (AD).
2. • To determine if any reduction/reversal of amyloid accumulation in the brain of patients with AD in response to NPI-001, administered orally.
3. • To assess the effects of NPI-001 on phospho Tau217 (pTau217) and total Tau (tTau) protein levels in plasma and on pTau/tTau ratio
4. • To assess the effects of NPI-001 on NFL in plasma
5. • To assess the effect of NPI-001 on cognitive status of patients with AD.
6. • To characterize pharmacokinetic parameters of NPI-001 in a subset of 5 participants with AD.

Conditions and MedDRA coding

Alzheimer's Disease

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

IPD plan description

There are no plans to share individual participant data

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subject is male or female, aged 50 or older but younger than 85.
2. Subject has MCI or mild dementia due to Alzheimer´s disease according to Jack 2024 with a CDR of 0.5 or 1.0 receiving standard AD care
3. Subject is willing to have a baseline and follow up blood tests according to the schedule of assessments, for up to 12 months.
4. Subject is willing and able to undergo MRI, and amyloid PET scan evaluations of the brain which fulfil the following requirements:a.PET amyloid brain load >32 centiloids b. MRI <8 micro bleeds.
5. Subject has provided informed consent for participation in trial.
6. Subject has a spouse/close relative/caregiver as study partner who lives with or supervises subject care.
7. Subject has an MMSE score of >21 < 28
8. If taking concomitant medications, treated with stable doses of drugs essentially required for chronic medical conditions which do not lead to exclusion, during a period of at least 3 months prior to screening, and dose regimen is expected to remain stable during the conduct of the study.
9. Subject is able to read, write, speak clearly for the cognitive tests, with eyesight and hearing sufficient to enable completion of the cognitive tests.
10. Subject has a pTau 217 value of > 0.35 pg/ml

Exclusion criteria 11

1. Subject has MRI evidence evaluated by central read of a. Brain abnormality caused by other neurological disease than AD including but not limited to vascular disease (vascular dementia), acute or subacute cerebral hemorrhage, large-vessel stroke, brain tumors, inflammatory immunological or metabolic disorders. b. more than 7 microbleeds, multiple lacunes or any lacune in strategically important location, Grade 2 and 3 white matter lesions, any focal area of superficial siderosis or medical implants or foreign bodies unsuitable for MRI.
2. Use of NAC or other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 14 days, whichever is longer.
3. Subject has moderate or severe dementia, defined as CDR of ≥ 2.0
4. History of liver disease
5. Any suicidal ideation or suicidal behavior in the C-SSRS (C-SSRS score > 0)
6. Subjects who are or have been on AD immunotherapy.
7. Subject has MRI evidence of vascular disease (vascular dementia).
8. Subject has clinically significant illness, mental or physical, that, in the opinion of the investigator, might confound the results of the study, pose additional risk to the patient by their participation, or prevent/impede the patient from completing the study.
9. Subject has known sensitivity to NAC/NACA.
10. Known or recently suspected (3 months) excessive alcohol or drug abuse.
11. There is any concern by the investigator regarding the patient’s safety, compliance, or suitability with respect to his/her participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • Treatment-Emergent Adverse Events and Serious Adverse Events., clinical lab values, electrocardiogram, physical examination, vital signs. ARIA MRI classification

Secondary endpoints 8

1. • Reduction in toxic amyloid oligomers in plasma samples at 3, 6, 9 and 12 months of therapy.
2. • Reduction in amyloid accumulation in the brain following 12 months of therapy.
3. • Reduction in pTau217 and pTau217/tTau ratio in plasma samples at 3, 6, 9 and 12 months of therapy.
4. • Reduction in NFL in plasma samples at 3, 6, 9 and 12 months of therapy.
5. • Neuropsychological Test Battery (NTB), Change in Clinical Dementia Rating (CDR) Scale, ADAScog and ADL (ADCS-ADL-MCI) following 12 months of therapy.
6. • Plasma concentrations of NPI-001 will be measured after the first intake of NPI-001 and after 12 months of intake on eight occasions up to 24hr.
7. • The following PK parameters will be determined: Cmax, Tmax and AUC0-24h.apparent T1/2
8. • Change from baseline in Clinical Dementia Rating (CDR) Scale, ADAS-Cog, Columbia Suicide Severity Rating Scale (C-SSRS) following 12 months of therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arctic Therapeutics ehf.

Sponsor organisation

Arctic Therapeutics ehf.

Address

Bjargargata 1

City

Reykjavik

Postcode

102

Country

Iceland

Scientific contact point

Organisation

Arctic Therapeutics ehf.

Contact name

Ivar Hakonarson

Public contact point

Organisation

Arctic Therapeutics ehf.

Contact name

Ivar Hakonarson

Third parties 2

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications