Hereditary Cystatin C Amyloid Angiopathy (HCCAA)Phase 2HCCAANCT07716865
Safety, Tolerability and Efficacy of NPI-001 in Patients With Hereditary Cystatin C Amyloid Angiopathy (HCCAA)
A Phase 2 study testing NACA in people with Hereditary Cystatin C Amyloid Angiopathy (HCCAA) and Hemorrhage Brain, run by Arctic Therapeutics at 1 site in Iceland.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Hereditary Cystatin C Amyloid Angiopathy (HCCAA), Hemorrhage Brain, Hemorrhage Cerebral
- What is being tested?
- NACA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteIceland
- Study dates
- 3 Apr 2024to 31 Jan 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.*
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Being tested
- NACA
- Keywords
- HCCAA, rare dementia, familial dementia, cystatin C amyloid angiopathy, CAA
- Medical subject headings
- Cerebral Amyloid Angiopathy, Familial, Intracranial Hemorrhages, Cerebral Hemorrhage, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NACADrug
Also called AT-001, NAC-amid
250 mg tablets BID, increasing dosage from 250 mg BID to 750 mg BID
| Study group | Role | What they receive |
|---|---|---|
| Landspitali University Hospital | Experimental | All participants receive active treatment in the form of tablets administered twice per day. Receives: Drug: NACA |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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.
Measured: Through study completion, up to 24 months
Secondary outcomes (1)
Biomarker - cystatin C aggregation in the skin
Reduction in amyloid-cystatin C complexes in skin biopsies compared with baseline levels based on % of area stained using Immunohistochemistry
Measured: Through study completion, up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2026
- Study start3 Apr 2024
- Primary completion29 Dec 2026 (estimated)
- Study completion31 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary Cystatin C Amyloid Angiopathy (HCCAA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arctic Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07716865
- Sponsor's protocol ID
- AT-23-01
- Other IDs
- 2023-503969-36-01, 2023
- Acronym
- HCCAA
- Status last verified
- Jul 2026
- First submitted
- 18 Mar 2026
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33758187
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability and Efficacy of NPI-001 in Patients With Hereditary Cystatin C Amyloid Angiopathy (HCCAA)
- ClinicalTrials.gov ID
- NCT07716865
- Acronym / sponsor ID
- HCCAA / AT-23-01
- Keywords
- HCCAA, rare dementia, familial dementia, cystatin C amyloid angiopathy, CAA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Arctic TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 3 Apr 2024 (actual)
- Primary completion
- 29 Dec 2026 (estimated)
- Study completion
- 31 Jan 2027 (estimated)
- First posted
- 21 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Landspitali University Hospital | Experimental | Drug: NACAAll participants receive active treatment in the form of tablets administered twice per day. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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.*
Key exclusion criteria (11 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NACAAlso: AT-001, NAC-amid250 mg tablets BID, increasing dosage from 250 mg BID to 750 mg BID | Drug | Landspitali University Hospital |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: Through study completion, up to 24 months
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.
Frequency of cerebral bleeding events
Time frame: Through study completion, up to 24 months
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)
Safety labs results within normal range
Time frame: Through study completion, up to 24 months
Safety labs result not being outside of normal ranges and/or not clinically significant as assessed by the PI.
1 secondary outcome
Biomarker - cystatin C aggregation in the skin
Time frame: Through study completion, up to 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Background: PubMed 33758187March 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NACA in people with Hereditary Cystatin C Amyloid Angiopathy (HCCAA) and Hemorrhage Brain, run by Arctic Therapeutics at 1 site in Iceland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iceland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: Through study completion, up to 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07716865, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.