Alzheimer´s Disease
Conditions
Keywords
Alzheimer´s disease, Mild Cognitive Impairment, Dementia
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.
Interventions
DRUGNPI-001
NPI-001 tablets administered orally BID at escalating doses of 250 mg, 500 mg, and 750 mg for period of 12 months
DRUGPlacebo
Placebo tablets administered orally BID at escalating doses of 250 mg, 500 mg, and 750 mg for period of 12 months
Sponsors
Arctic Therapeutics
Blueskin AS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has provided informed consent for participation in trial. 2. Subject is male or female, aged 50 or older but younger than 85. 1. 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. 2. 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. 3. 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). 4. Subject has an MMSE score of \>21 \< 28 5. Subject is willing to have a baseline and follow up blood tests according to the schedule of assessments, for up to 12 months. 6. Subject has a pTau 217 value of \> 0.35 pg/ml 7. Subject is willing and able to undergo MRI, and amyloid PET scan evaluations of the brain, which fulfill the following requirements: 1. PET amyloid brain load \>32 centiloids 2. MRI \<8 micro bleeds 8. Subject has a spouse/close relative/caregiver as study partner who lives with him/her or supervises subject care. The caregiver must be willing to accompany the subject to all study visits and able to give informed consent for their own participation and be able to read and write. 9. 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. 10. Subject is able to read, write, speak clearly for the cognitive tests, with eyesight and hearing sufficient to enable completion of the cognitive tests.
Exclusion criteria
1. Subject has MRI evidence evaluated by central read of 1. 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. 2. 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. Subject has moderate or severe dementia, defined as CDR of ≥ 2.0 3. 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. 4. Subject has known sensitivity to NAC/NACA. 5. Known or recently suspected (3 months) excessive alcohol or drug abuse. 6. History of liver disease. 7. There is any concern by the investigator regarding the subject's safety, compliance, or suitability with respect to his/her participation in the study. 8. 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. 9. Subjects who are or have been on AD immunotherapy. 10. Any suicidal ideation or suicidal behavior in the C-SSRS (C-SSRS score \> 0)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment -Emergent Adverse Events | Through study completion, approximately up to 14 months | 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. |
| Safety labs results within normal range | Through study completion, approximately up to 14 months | Safety labs result not being outside of normal ranges and/or not clinically significant as assessed by the PI. |
| Assessment of ARIA H and ARIA E in the brain with MRI imaging | Through study completion, approximately up to 14 months | MRI imaging to assess ARIA H and ARIA E in the brain by ARIA MRI classification. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biomarker 1: Assessment of reduction in toxic amyloid oligomers in plasma samples | Through study completion, until 12 months | Reduction in toxic amyloid oligomers in plasma samples at 3, 6, 9 and 12 months of therapy measured by SOBA method. |
| Biomarker 2: Assessment of the effects of NPI-001 on pTau217 levels in plasma | Through study completion, until 12 months | Reduction in pTau217 in plasma samples at 3, 6, 9 and 12 months of therapy measured by Simoa technology. |
| Biomarker 3: Assessment of the effects of NPI-001 on NFL in plasma | Through study completion, until 12 months | Reduction in NFL in plasma samples at 3, 6, 9 and 12 months of therapy assessed by ELISA. |
| Biomarker 4: Assessment of reduction in amyloid accumulation in the brain following 12 months of therapy (PET) | Through study completion, until 12 months | To determine if any reduction/reversal of amyloid accumulation in the brain of subjects with AD in response to NPI-001, administered orally. |
Countries
Denmark, Iceland
Outcome results
None listed