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.
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
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
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- 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
Australia2 sites
Clinical Trial Site
Camperdown, 2050
Clinical Trial Site
Parkville, 3050
Canada2 sites
Clinical Trial Site
Mount Royal, H3P 3P1
Clinical Trial Site
Toronto, M5B 1W8
France2 sites
Clinical Trial Site
Bordeaux, 33000
Clinical Trial Site
Bron, 69500
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
- Conditions
- Hereditary Hemorrhagic Telangiectasia
- 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 group | Role | What they receive |
|---|---|---|
| Part A: ALN-6400 | Experimental | Participants will be administered a single dose of ALN-6400. Receives: Drug: ALN-6400 |
| Part A: Placebo | Placebo comparator | Participants will be administered a single dose of placebo. Receives: Drug: Placebo |
| Part B: ALN-6400 | Experimental | Participants will be administered multiple doses of ALN-6400. Receives: Drug: ALN-6400 |
| Part B: Placebo | Placebo comparator | Participants 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.
Part A: Frequency of Adverse Events
Measured: Up to Week 36
Part B: Frequency of Adverse Events
Measured: Up to Week 96
Secondary outcomes (17)
Part A: Concentrations of ALN-6400 in Plasma
Measured: Predose and up to 2 days postdose
Part A: Change from Baseline in Plasminogen (PLG) in Plasma Protein Levels
Measured: Predose and up to Week 36 postdose
Part B: Change from Baseline in Plasminogen (PLG) in Plasma Protein Levels
Measured: Screening and up to Week 96 postdose
Part A: Change from Baseline in Plasminogen (PLG) in Plasma Activity Levels
Measured: Predose and up to Week 36 postdose
Part B: Change from Baseline in Plasminogen (PLG) in Plasma Activity Levels
Measured: Part B: Screening and up to Week 96 postdose
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
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
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
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
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
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
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
Part B: Change from Baseline in Iron Infusions
Measured: Baseline up to Week 96
Part B: Change from Baseline in Red Blood Cell (RBC) Infusions
Measured: Baseline up to Week 96
Part B: Change from Baseline in Hemoglobin
Measured: Baseline up to Week 96
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
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.
- First posted26 Oct 2024
- Study start7 Nov 2024
- Primary completion5 Jan 2028 (estimated)
- Study completion22 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Hemorrhagic TelangiectasiaStudies of the same condition, open and under way.
- More trials run by Alnylam PharmaceuticalsThe sponsor's other registered studies.
- 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 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)
Sponsor and investigators
- Lead sponsor
- Alnylam Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Alnylam Pharmaceuticals
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.