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Hereditary Hemorrhagic TelangiectasiaPhase 1/2InsigHHTNCT06659640

A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

A Phase 1/2 study testing ALN-6400 in people with Hereditary Hemorrhagic Telangiectasia, run by Alnylam Pharmaceuticals at 16 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

The purpose of this study is to: evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-6400 in healthy volunteers evaluate the efficacy, safety, tolerability and PD of multiple doses of ALN-6400 in adult patients with HHT Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Hereditary Hemorrhagic Telangiectasia
What is being tested?
ALN-6400
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
89 participants
Where
16 sitesin 6 countries
Study dates
7 Nov 2024to 22 Jun 2028
Phase
Phase 1/2
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 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Part A:
  • Is a healthy adult volunteer
  • Part B:
  • Is an adult patient with a clinical diagnosis of HHT

Who cannot join

  • Part A:
  • Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > upper limit of normal (ULN)
  • Has known human immunodeficiency virus (HIV) infection; or known current or chronic hepatitis C virus or hepatitis B virus infection
  • Has an estimated glomerular filtration (eGFR) of <90 mL/min/1.73m^2 at screening
  • Part B:
  • Has ALT or AST >2×ULN
Show all 11Show fewer
  • Has total bilirubin >1.5×ULN
  • Has eGFR of <30 mL/min/1.73m^2 at screening
  • Parts A and B:
  • Is not willing to comply with the contraceptive requirements during the study period
  • Note: other protocol defined inclusion / exclusion criteria apply

Trial locations and contacts

16 sites in 6 countries.

16 sites in 6 countries

United States8 sites

  • Clinical Trial Site

    Birmingham, Alabama, 35249

  • Clinical Trial Site

    Boston, Massachusetts, 02114

  • Clinical Trial Site

    Chapel Hill, North Carolina, 27514

  • Clinical Trial Site

    Cypress, California, 90630

  • Clinical Trial Site

    Gainesville, Florida, 32608

  • Clinical Trial Site

    Indianapolis, Indiana, 46260

  • Clinical Trial Site

    Rochester, Minnesota, 55905

  • Clinical Trial Site

    St Louis, Missouri, 63110

Other trials in United States

Australia2 sites

  • Clinical Trial Site

    Camperdown, 2050

  • Clinical Trial Site

    Parkville, 3050

Other trials in Australia

Canada2 sites

  • Clinical Trial Site

    Mount Royal, H3P 3P1

  • Clinical Trial Site

    Toronto, M5B 1W8

Other trials in Canada

France2 sites

  • Clinical Trial Site

    Bordeaux, 33000

  • Clinical Trial Site

    Bron, 69500

Other trials in France

Germany1 site

  • Clinical Trial Site

    Homburg, 66421

Other trials in Germany

Spain1 site

  • Clinical Trial Site

    L'Hospitalet de Llobregat, 8907

Other trials in Spain

About this study

Official title: InsigHHT: A Phase 1/2, Randomized, Double-blind, Placebo-controlled, 2-part Study of the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Single Dose ALN-6400 in Adult Healthy Volunteers and Multiple Dose ALN-6400 in Adult Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

The purpose of this study is to:

  • evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of ALN-6400 in healthy volunteers
  • evaluate the efficacy, safety, tolerability and PD of multiple doses of ALN-6400 in adult patients with HHT
Being tested
ALN-6400, Placebo
Keywords
siRNA, RNAi therapeutic, Plasminogen, PLG, HHT, Osler-Weber-Rendu, epistaxis
Medical subject headings
Telangiectasia, Hereditary Hemorrhagic, Epistaxis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ALN-6400Drug

    ALN-6400 will be administered subcutaneously (SC)

  • PlaceboDrug

    Placebo will be administered subcutaneously (SC)

Study groups in NCT06659640
Study groupRoleWhat they receive
Part A: ALN-6400ExperimentalParticipants will be administered a single dose of ALN-6400.
Receives: Drug: ALN-6400
Part A: PlaceboPlacebo comparatorParticipants will be administered a single dose of placebo.
Receives: Drug: Placebo
Part B: ALN-6400ExperimentalParticipants will be administered multiple doses of ALN-6400.
Receives: Drug: ALN-6400
Part B: PlaceboPlacebo comparatorParticipants will be administered multiple doses of placebo.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Frequency of Adverse Events

    Measured: Up to Week 36

  2. Part B: Frequency of Adverse Events

    Measured: Up to Week 96

Secondary outcomes (17)

  1. Part A: Concentrations of ALN-6400 in Plasma

    Measured: Predose and up to 2 days postdose

  2. Part A: Change from Baseline in Plasminogen (PLG) in Plasma Protein Levels

    Measured: Predose and up to Week 36 postdose

  3. Part B: Change from Baseline in Plasminogen (PLG) in Plasma Protein Levels

    Measured: Screening and up to Week 96 postdose

  4. Part A: Change from Baseline in Plasminogen (PLG) in Plasma Activity Levels

    Measured: Predose and up to Week 36 postdose

  5. Part B: Change from Baseline in Plasminogen (PLG) in Plasma Activity Levels

    Measured: Part B: Screening and up to Week 96 postdose

  6. Part B: Change from Baseline in Intensity-adjusted Epistaxis Duration

    Intensity-adjusted epistaxis duration will be assessed using a daily patient epistaxis diary.

    Measured: Baseline up to Week 96

  7. Part B: Change from Baseline in Epistaxis Severity Score (ESS) Scale

    Validated bleeding scale in HHT scored between 0-10, higher scores indicate worse bleeding.

    Measured: Baseline up to Week 96

  8. Part B: Change from Baseline in Epistaxis Duration

    Epistaxis duration will be assessed using a daily patient epistaxis diary.

    Measured: Baseline up to Week 96

  9. Part B: Change from Baseline in Epistaxis Frequency

    Epistaxis frequency will be assessed using a daily patient epistaxis diary.

    Measured: Baseline up to Week 96

  10. Part B: Change from Baseline in Epistaxis Intensity

    Epistaxis intensity will be assessed using a daily patient epistaxis diary.

    Measured: Baseline up to Week 96

  11. Part B: Change from Baseline in Epistaxis-free Days per Month

    Epistaxis-free days per month will be assessed using a daily patient epistaxis diary.

    Measured: Baseline up to Week 96

  12. Part B: Change from Baseline in Hematologic Support Score (HSS)

    The HSS is a quantitative tool designed to longitudinally assess the red blood cells (RBC) and iron supplementation needs of patients with HHT and other chronic bleeding disorders.

    Measured: Baseline up to Week 96

  13. Part B: Change from Baseline in Iron Infusions

    Measured: Baseline up to Week 96

  14. Part B: Change from Baseline in Red Blood Cell (RBC) Infusions

    Measured: Baseline up to Week 96

  15. Part B: Change from Baseline in Hemoglobin

    Measured: Baseline up to Week 96

  16. Part B: Change from Baseline in Quality of Life Patient-reported Outcomes (QoL/PRO) assessed by Nasal Outcome Score for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NOSE HHT) Score

    HHT-specific QoL/PRO will be assessed using the NOSE HHT score. The NOSE HHT is a 29-item patient-reported, clinically validated outcome measure, with total scores ranging continuously from 0 to 4 with higher scores indicating worse scores.

    Measured: Baseline up to Week 84

  17. Part B: Change from Baseline in QoL/PRO assessed by Modified Patient Global Impression of Severity (mPGI-S) Score

    HHT-specific QoL/PRO will be assessed using the mPGI-S. The patient will respond to a single question, providing their global impression of change in their overall status and epistaxis experience.

    Measured: Baseline up to Week 84

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2024
  2. Study start7 Nov 2024
  3. Primary completion5 Jan 2028 (estimated)
  4. Study completion22 Jun 2028 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06659640
Sponsor's protocol ID
ALN-6400-001
Other IDs
2025-522510-23-00, 2025
Acronym
InsigHHT
Status last verified
Oct 2026
First submitted
24 Oct 2024
Last updated
15 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Phase 2-4: Access to Anonymized individual participant data that support these results is made available 12 months after study completion and not less than 12 months after the product and indication have been approved in the United States (US) and/or the European Union (EU). Data will be provided contingent upon the approval of a research proposal and the execution of a data sharing agreement. Requests for access to data can be submitted via the website www.vivli.org.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ALN-6400 in people with Hereditary Hemorrhagic Telangiectasia, run by Alnylam Pharmaceuticals at 16 sites in 6 countries.

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 4 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 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States, Australia, Canada, France, Germany and 1 more country. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Part A: Frequency of Adverse Events (time frame: Up to Week 36). The study lists 2 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 NCT06659640.

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 15 Oct 2026.

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