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NCT Number: NCT06659640

A Study to Evaluate ALN-6400 in Healthy Volunteers and 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

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Hereditary Hemorrhagic Telangiectasia Cardiovascular Abnormalities Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Epistaxis Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhage Hemorrhagic Disorders Hemostatic Disorders Nose Diseases Otorhinolaryngologic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Signs and Symptoms Signs and Symptoms, Respiratory Telangiectasia, Hereditary Hemorrhagic Telangiectasis Vascular Diseases Vascular Malformations

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Clinical Trial Site, Camperdown, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

-

Part A:

  • Is a healthy adult volunteer

Part B:

  • Is an adult patient with a clinical diagnosis of HHT

Exclusion criteria

-

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
  • 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

Treatment and study plan

ALN-6400

Drug

ALN-6400 will be administered subcutaneously (SC)

Placebo

Drug

Placebo will be administered subcutaneously (SC)

Primary outcomes

  1. Part A: Frequency of Adverse Events

    Time frame: Up to Week 36

  2. Part B: Frequency of Adverse Events

    Time frame: Up to Week 96

Secondary outcomes

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

    Time frame: Predose and up to 2 days postdose

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

    Time frame: Predose and up to Week 36 postdose

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

    Time frame: Screening and up to Week 96 postdose

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

    Time frame: Predose and up to Week 36 postdose

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

    Time frame: Part B: Screening and up to Week 96 postdose

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

    Time frame: Baseline up to Week 96

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

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

    Time frame: Baseline up to Week 96

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

  8. Part B: Change from Baseline in Epistaxis Duration

    Time frame: Baseline up to Week 96

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

  9. Part B: Change from Baseline in Epistaxis Frequency

    Time frame: Baseline up to Week 96

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

  10. Part B: Change from Baseline in Epistaxis Intensity

    Time frame: Baseline up to Week 96

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

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

    Time frame: Baseline up to Week 96

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

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

    Time frame: Baseline up to Week 96

    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.

  13. Part B: Change from Baseline in Iron Infusions

    Time frame: Baseline up to Week 96

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

    Time frame: Baseline up to Week 96

  15. Part B: Change from Baseline in Hemoglobin

    Time frame: 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

    Time frame: Baseline up to Week 84

    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.

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

    Time frame: Baseline up to Week 84

    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.

Sponsors and collaborators

Lead sponsor

Alnylam Pharmaceuticals

Industry

Registry information

Official study 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)

Acronym: InsigHHT

Important dates

Study start
2024
Primary completion
2028
Study completion
2028
First posted
Oct 26, 2024
Registry last updated
Jul 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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