Acetylcysteine amide (N-acetylcysteine amide; NACA) for Hereditary Cystatin C Amyloid Angiopathy (HCCAA)|Cerebral amyloid angiopathy

Inclusion criteria

• {"criterion_text":"- 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."}
• {"criterion_text":"- Patient has been genotyped/sequenced and confirmed to carry the L68Q mutation in the cystatin C gene."}
• {"criterion_text":"- Patients with previously established cystatin C/amyloid protein complexes in the skin"}
• {"criterion_text":"- Patients with mild cognitive impairment with cognitive function to follow the study protocol."}
• {"criterion_text":"- 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. *(N/A for patients participating in the additional PK cohort only)"}
• {"criterion_text":"- 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. *(N/A for patients participating in the additional PK cohort only)"}
• {"criterion_text":"- Patient is willing to undergo MRI evaluations of the brain. *(N/A for patients participating in the additional PK cohort only)"}
• {"criterion_text":"- Patient has provided informed consent for participation in trial."}
• {"criterion_text":"- 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

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

Primary endpoints

• {"endpoint_text":"- Safety •\tTreatment-Emergent Adverse Events and Serious Adverse Events, vital signs, ECG, physical and neurological examination, safety laboratory blood and urinalysis after a single dose of 250 mg and 750 mg of NACA (PK cohort), 12 months of treatment (main study) and after 24 months of treatment (OLE phase)","definition_or_measurement_approach":"Assessment of TEAEs and SAEs, vital signs, ECG, physical and neurological examinations, safety laboratory blood and urinalysis measured after single PK doses (250 mg and 750 mg) for PK cohort, after 12 months of treatment in main study and after 24 months in OLE phase."}
• {"endpoint_text":"- Efficacy •\tFrequency 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 (OLE phase)","definition_or_measurement_approach":"Counting frequency of clinical cerebral bleeding events; defined as any bleed that causes stroke (hemorrhagic or ischemic), assessed after 12 months (main study) and after 24 months (OLE)."}

Secondary endpoints

• {"endpoint_text":"- •\tClinical Dementia Rating (DSR-2) Scale","definition_or_measurement_approach":"Clinical Dementia Rating (DSR-2) Scale assessments to measure cognitive status."}
• {"endpoint_text":"- •\tDeaths","definition_or_measurement_approach":"All-cause deaths recorded during study period."}
• {"endpoint_text":"- •\tLevels of cystatin C/amyloid dimers/oligomiers/polymers vs monomers of same","definition_or_measurement_approach":"Measurement of cystatin C/amyloid oligomeric and monomeric species levels (biomarker assays) comparing baseline and on-treatment samples."}
• {"endpoint_text":"- •\tLevels of glutathione and GSSG/GSH ratios in plasma","definition_or_measurement_approach":"Plasma glutathione quantification and calculation of GSSG/GSH ratios."}
• {"endpoint_text":"- •\thCC levels in urine","definition_or_measurement_approach":"Measurement of hCC levels in urine samples."}
• {"endpoint_text":"- •\tPlasma concentrations of NPI-001 PK parameters: Cmax, Tmax and AUC0-24h and T1/2 for single dose of 250mg or 750mg (and steady state for subjects participating in the main study)","definition_or_measurement_approach":"Pharmacokinetic sampling to determine Cmax, Tmax, AUC0-24h and T1/2 after single doses (250 mg or 750 mg) and at steady state for main study participants."}
• {"endpoint_text":"- •\tSkin deposition of cystatin C/amyloid protein complex, including monomer vs dimer (and other high-molecular versions of same) ratios, together with skin collagen deposition and cell surface marker activation (vimentin, SMAD/WNT-1) which are correlated","definition_or_measurement_approach":"Skin biopsy biomarker analyses including quantification of cystatin C/amyloid complexes, monomer:dimer ratios, collagen deposition and cell-surface marker activation assessed by cryoEM/Western blot and related assays."}
• {"endpoint_text":"- •\t(1) Clinical impact in terms on speech, paralysis and how quickly symptoms reverse (2) CT scan to assess size, distribution and resolution of hemorrhage in the brain","definition_or_measurement_approach":"Clinical neurological assessments (speech, paralysis, symptom recovery) and CT imaging to assess hemorrhage size, distribution and resolution."}

Iceland

Earliest CTIS Part Ii Submission Date

14-02-2024

Latest Decision Or Authorization Date

15-09-2025

Processing Time Days

579

Number Of Sites

1

Number Of Participants

25

Primary sponsor

Full Name

Arctic Therapeutics ehf.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Iceland

Contract research organisations

Name

Regenold GmbH

Responsibilities

XEVPMD management, CTIS management & CT application submission

Third parties

• {"country":"Germany","full_name":"Regenold GmbH","duties_or_roles":"sponsorDuties codes: 12; 15: XEVPMD management, CTIS management & CT application submission; 5; 8","organisation_type":"Pharmaceutical company"}