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

Inclusion criteria

• Patient is male or female, aged 12 or older, and of Icelandic ancestry (see section 5.1 Selection of Trial Population). Subjects 12-17 years old will only qualify for inclusion if the DSMB approves lowering the minimum age following review of at least 3 months of safety in adults.
• 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.

Exclusion criteria

• 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.