Safety, Tolerability and Biomarker-based Efficacy of NPI-001 (AT-001) in Subjects With MCI or Alzheimer's Disease (AD)

NCT07741526 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: AT-24-032024-519497-39-00
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 4

Brief Summary

The study aims to measure safety, tolerability and biomarker-based efficacy of NPI-001 (AT-001) in Subjects with MCI or Alzheimer's Disease (AD). In the study participants receive increasing dose of active treatment (250mg vs 500mg vs 750mg) or matched placebo in the form of tablets BID.

Conditions

Alzheimer´s Disease

Keywords

Alzheimer´s disease; Mild Cognitive Impairment; Dementia

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment -Emergent Adverse Events

  Incidence of Treatment -Emergent Adverse Events in response to NPI (AT-001) administered orally in subjects with Alzheimer's disease (AD). Assessment of the number of participants with treatment-related adverse events. Assessment of the amount of mild and severe adverse events related to the treatment.

  Through study completion, approximately up to 14 months

• Safety labs results within normal range

  Safety labs result not being outside of normal ranges and/or not clinically significant as assessed by the PI.

  Through study completion, approximately up to 14 months

• Assessment of ARIA H and ARIA E in the brain with MRI imaging

  MRI imaging to assess ARIA H and ARIA E in the brain by ARIA MRI classification.

  Through study completion, approximately up to 14 months

Secondary Outcomes (4)

• Biomarker 1: Assessment of reduction in toxic amyloid oligomers in plasma samples

  Through study completion, until 12 months

• Biomarker 2: Assessment of the effects of NPI-001 on pTau217 levels in plasma

  Through study completion, until 12 months

• Biomarker 3: Assessment of the effects of NPI-001 on NFL in plasma

  Through study completion, until 12 months

• Biomarker 4: Assessment of reduction in amyloid accumulation in the brain following 12 months of therapy (PET)

  Through study completion, until 12 months

Study Arms (2)

Active treatment + SOC

EXPERIMENTAL

The group receives increasing dose of the active treatment and SOC

Drug: NPI-001

Placebo + SOC

PLACEBO COMPARATOR

The group receives dose of the placebo and SOC

Drug: Placebo

Interventions

NPI-001 DRUG

NPI-001 tablets administered orally BID at escalating doses of 250 mg, 500 mg, and 750 mg for period of 12 months

Active treatment + SOC

Placebo DRUG

Placebo tablets administered orally BID at escalating doses of 250 mg, 500 mg, and 750 mg for period of 12 months

Placebo + SOC

Eligibility Criteria

• Age: 50 Years - 84 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent for participation in trial.
• Subject is male or female, aged 50 or older but younger than 85.
• Female Subjects:
• Of child-bearing potential in the age range of 50-60 years who are still menstruating, are willing to perform a pregnancy test at screening visit, V1 (Baseline) and at each subsequent visit and adhere to contraception requirements.
• Of nonchildbearing Potential (WONCBP), women in the following categories are considered WONCBP: Premenopausal female permanently sterile due to one of the following (for the purpose of this study): Women who have documented hysterectomy, documented bilateral salpingectomy, documented bilateral oophorectomy
• Postmenopausal female is defined as no menses for 12 months. If confirmation is needed, a high follicle stimulating hormone (FSH) level in the postmenopausal range will be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). Females on HRT and whose menopausal status is in doubt must discontinue HRT to allow confirmation of postmenopausal status before study enrollment.
• Male subjects:
• Male subjects with female partners of child-bearing potential who are willing or able to adhere to contraception requirements, or male subjects with documented infertility.
• 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 (SOC) (65).
• Subject has an MMSE score of \>21 \< 28
• Subject is willing to have a baseline and follow up blood tests according to the schedule of assessments, for up to 12 months.
• Subject has a pTau 217 value of \> 0.35 pg/ml
• Subject is willing and able to undergo MRI, and amyloid PET scan evaluations of the brain, which fulfill the following requirements:
• PET amyloid brain load \>32 centiloids
• MRI \<8 micro bleeds

You may not qualify if:

• Subject has MRI evidence evaluated by central read of
• 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.
• 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.
• Subject has moderate or severe dementia, defined as CDR of ≥ 2.0
• 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 Subject by their participation, or prevent/impede the subject from completing the study.
• Subject has known sensitivity to NAC/NACA.
• Known or recently suspected (3 months) excessive alcohol or drug abuse.
• History of liver disease.
• There is any concern by the investigator regarding the subject's safety, compliance, or suitability with respect to his/her participation in the study.
• 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.
• Subjects who are or have been on AD immunotherapy.
• Any suicidal ideation or suicidal behavior in the C-SSRS (C-SSRS score \> 0)

Sponsors & Collaborators

• Arctic Therapeutics: lead
• Blueskin AS: collaborator

Study Sites (4)

Sanos Clinic Gandrup

Gandrup, Denmark

Location

Sanos Clinic Herlev

Herlev, Denmark

Location

Sanos Clinic Vejle

Vejle, Denmark

Location

Landspitali University Hospital

Reykjavik, 108, Iceland

Location

Related Links

• Related Info

MeSH Terms

Conditions

Cognitive Dysfunction; Dementia

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

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: March 18, 2026
• First Posted: August 3, 2026
• Study Start: October 14, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: August 3, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IC (1); DK (3)