Safety, Tolerability and Efficacy of NPI-001 in Patients With Hereditary Cystatin C Amyloid Angiopathy (HCCAA)

NCT07716865 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: AT-23-012023-503969-36-01
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to measure safety, tolerability and biomarker-based efficacy of NPI-001 (AT-001) in Subjects with Hereditary Cystatin C Amyloid Angiopathy (HCCAA). In the study participants receive increasing dose or active treatment (250 mg vs 500mg vs 750 mg) or matched placebo in the form of tablets BID.

Conditions

Hereditary Cystatin C Amyloid Angiopathy (HCCAA); Hemorrhage Brain; Hemorrhage Cerebral

Keywords

HCCAA; rare dementia; familial dementia; cystatin C amyloid angiopathy; CAA

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events

  Incidence of Treatment-Emergent Adverse Events in response to NPI-001 (AT-001) administered orally in subjects with HCCAA. 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, up to 24 months

• Frequency of cerebral bleeding events

  Assessment of frequency of clinical cerebral bleedings events, defined as any bleed that causes stroke, hemorrhagic or ischemic after 12 months of treatment (main study) and after 24 months of treatment (12 - months study extension phase)

  Through study completion, up to 24 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, up to 24 months

Secondary Outcomes (1)

• Biomarker - cystatin C aggregation in the skin

  Through study completion, up to 24 months

Study Arms (1)

Landspitali University Hospital

EXPERIMENTAL

All participants receive active treatment in the form of tablets administered twice per day.

Drug: NACA

Interventions

NACA DRUG

250 mg tablets BID, increasing dosage from 250 mg BID to 750 mg BID

Also known as: AT-001, NAC-amid

Landspitali University Hospital

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has been genotyped/sequenced and confirmed to carry the L68Q mutation in the cystatin C gene.
• Patients with previously established cystatin C/amyloid protein complexes in the skin
• Patients with mild cognitive impairment with cognitive function to follow the study protocol.
• Patient is willing to have a baseline and follow up skin biopsies according to the schedule of assessments, for up to 12 months, and up to 24 months if participating in the extension phase.\*
• Patient is willing to have a baseline and follow up blood tests according to the schedule of assessments, for up to 12 months, and up to 24 months if participating in the extension phase.\*
• Patient is willing to undergo MRI evaluations of the brain.\*
• Patient has provided informed consent for participation in trial.
• Patient is willing and able to use contraception consistent with local regulations regarding the methods for participants in the clinical trial.
• Both female participants of childbearing potential and male participants able to father children must have (or have a partner who has) had a bilateral oophorectomy, hysterectomy or bilateral salpingectomy; must abstain from intercourse; or must agree to practice 2 acceptable methods of contraception throughout the course of the study and 4 weeks after the last visit. Acceptable methods of contraception include hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom), tubal ligation, and vasectomy.

You may not qualify if:

• Patient does not have L68Q mutation.
• Patients with moderate to severe cognitive impairment.
• Patient 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.
• Patient has known sensitivity to NAC
• Coagulation/clotting parameters clinically significant outside the normal range (platelet counts, aPTT, PT)
• Subject is not willing to cease NAC supplementation at least 2 weeks prior to study participation.
• Patient is pregnant or breastfeeding.
• Known or suspected excessive alcohol or drug abuse.
• There is any concern by the investigator regarding the patient's safety, compliance, or suitability with respect to his/her participation in the study.
• Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 14 days, whichever is longer.
• Patient is taking medications known to affect or be affected by CYP enzymes or transporters will be excluded to avoid any inference.

Sponsors & Collaborators

• Arctic Therapeutics: lead

Study Sites (1)

Landspitali University Hospital

Reykjavik, 108, Iceland

Location

Related Publications (1)

• March ME, Gutierrez-Uzquiza A, Snorradottir AO, Matsuoka LS, Balvis NF, Gestsson T, Nguyen K, Sleiman PMA, Kao C, Isaksson HJ, Bragason BT, Olafsson E, Palsdottir A, Hakonarson H. NAC blocks Cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients. Nat Commun. 2021 Mar 23;12(1):1827. doi: 10.1038/s41467-021-22120-4.

  PMID: 33758187 BACKGROUND

Related Links

• Related Info

MeSH Terms

Conditions

Cerebral Amyloid Angiopathy, Familial; Intracranial Hemorrhages; Cerebral Hemorrhage; Dementia

Interventions

caficrestat

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Cerebral Amyloid Angiopathy; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Vascular Diseases; Cardiovascular Diseases; Amyloidosis, Familial; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2026
• First Posted: July 21, 2026
• Study Start: April 3, 2024
• Primary Completion (Estimated): December 29, 2026
• Study Completion (Estimated): January 31, 2027
• Last Updated: July 21, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IC (1)