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A Study of ALN-6400 Safety and Effectiveness in Adults with Hereditary Hemorrhagic Telangiectasia

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What is this trial about?

A plain-language summary of the goals, design and what participants do

This study involves healthy adult volunteers and patients with Hereditary Hemorrhagic Telangiectasia, a condition where blood vessels do not form properly, leading to frequent nosebleeds and other bleeding problems. The study will test a treatment called ALN-6400, which is given as an injection under the skin. Some participants will receive ALN-6400 while others will receive placebo or phosphate-buffered saline, which is a salt water solution. The main goal of the study is to evaluate the safety and how well the body tolerates multiple doses of ALN-6400 in adult patients with this bleeding disorder.

The study is divided into two parts. The first part will test a single dose in healthy volunteers to understand how the body processes the medication and to check for any side effects. The second part will give multiple doses to patients who have been diagnosed with Hereditary Hemorrhagic Telangiectasia and experience moderate to severe nosebleeds. Patients in this part must have a history of frequent nosebleeds and may also have low levels of iron in their blood, requiring iron treatments or blood transfusions. During the study, researchers will monitor safety through physical examinations, heart tracings, and blood tests.

Throughout the study, researchers will measure changes in nosebleed frequency, duration, and severity using patient diaries and scoring systems. They will also track changes in blood protein levels, iron levels, and the need for iron infusions or blood transfusions. Quality of life will be assessed using questionnaires to understand how the treatment affects daily activities and breathing through the nose. The study will last several years and includes follow-up periods to continue monitoring the effects of the treatment over time.

The research process

The trial runs in 6 steps – from screening to follow-up. Each step says what happens and what the team monitors.

  1. Step 1

    Screening and preparation

    Your medical history will be reviewed to confirm the diagnosis of Hereditary Hemorrhagic Telangiectasia, which is a condition that causes abnormal blood vessel formation leading to bleeding.

    The diagnosis will be confirmed either through Curaçao criteria, which include symptoms such as recurrent nosebleeds, visible small blood vessels on skin or inside the mouth and nose, blood vessel abnormalities in internal organs, and family history of the condition, or through genetic testing.

    Your epistaxis severity score will be measured. This score assesses how severe your nosebleeds have been over the past four weeks. A score of 4 or higher is required, indicating moderate or severe nosebleeds.

    Blood tests will be performed to check for iron deficiency anemia, which means your blood has lower than normal levels of hemoglobin. For women, hemoglobin must be below 12.0 grams per deciliter, and for men, below 13.0 grams per deciliter. Alternatively, if you have received at least 250 milligrams of intravenous iron or at least one red blood cell transfusion within 24 weeks before screening, you may qualify.

    You will be asked to complete a daily diary to track your nosebleeds for at least one week during this screening period.

    Vital signs will be measured, and electrocardiograms will be performed to record the electrical activity of your heart.

    Additional laboratory tests will be conducted to assess your overall health.

  2. Step 2

    Treatment assignment

    You will be randomly assigned to receive either ALN-6400 or a placebo. A placebo is an inactive substance that looks like the actual medication but contains no active treatment.

    This is a double-blind study, which means neither you nor the medical staff will know which treatment you are receiving during the main treatment period.

  3. Step 3

    Double-blind treatment period

    You will receive multiple doses of either ALN-6400 or placebo through subcutaneous injection. This means the medication will be injected under your skin.

    The specific dosage, frequency, and duration of administration will be determined by the study protocol.

    Throughout this period, you must continue to complete your daily diary to record information about your nosebleeds, including how often they occur, how long they last, and how severe they are.

    You are expected not to undergo any procedures or surgeries to manage nasal bleeding during this period, except in emergency situations where it is medically necessary. Starting new treatments for bleeding related to your condition is also not permitted during this time. Routine nasal packing is allowed.

    Regular monitoring visits will be scheduled to assess your safety and response to treatment.

  4. Step 4

    Safety and efficacy assessments during treatment

    Your safety will be monitored through regular checks of vital signs, electrocardiograms, and laboratory tests.

    Any adverse events, which are unwanted or harmful reactions that may occur during treatment, will be recorded and evaluated.

    Blood samples will be collected to measure levels of plasminogen in your plasma. Plasminogen is a protein involved in blood clotting, and both its activity levels and protein levels will be assessed.

    Changes in your nosebleeds will be evaluated, including how long they last, how often they occur, how severe they are, and how many days per month you experience no nosebleeds. The epistaxis severity score will be measured again.

    Blood tests will be performed to check changes in your hemoglobin levels and to monitor if you require iron infusions or red blood cell transfusions. A hematologic severity score will also be calculated to assess the overall impact of bleeding on your blood health.

    Your quality of life will be assessed using questionnaires such as the NOSE HHT, which evaluates how nosebleeds affect your daily life, and the modified Patient Global Impression of Severity, which asks you to rate how severe your condition feels.

  5. Step 5

    Open-label extension period

    After completing the double-blind treatment period, you may be offered the opportunity to continue in an open-label extension period. During this phase, both you and the medical staff will know that you are receiving ALN-6400.

    You will continue to receive multiple doses of ALN-6400 through subcutaneous injection.

    During this period, procedures or surgeries to manage nasal bleeding and new therapies for bleeding are discouraged but not strictly prohibited.

    You will continue to complete your daily diary and attend regular monitoring visits.

    The same safety and efficacy assessments will continue, including monitoring of adverse events, vital signs, laboratory tests, changes in nosebleeds, blood health parameters, and quality of life.

  6. Step 6

    End of study

    After completing all treatment periods, a final assessment will be conducted.

    This will include a comprehensive review of your safety, changes in nosebleeds, blood health, and quality of life throughout the study.

    Final laboratory tests, vital signs measurements, and electrocardiograms will be performed.

    Your participation in the study will conclude after this final visit.

Who can join the trial?

6 criteria

  • You must be 18 years of age or older at the time you agree to join the study.
  • You must have a clinical diagnosis of Hereditary Hemorrhagic Telangiectasia, which is a condition that affects blood vessels. This diagnosis can be confirmed in one of two ways: either by meeting at least 3 out of 4 specific medical features (such as repeated nosebleeds, visible small red spots on skin or inside the mouth, abnormal blood vessel connections in internal organs, or having a close family member with this condition), or by having a genetic test that confirms the condition along with repeated nosebleeds.
  • You must have an epistaxis severity score of 4 or higher. Epistaxis means nosebleeds, and this score measures how moderate or severe your nosebleeds have been over the past 4 weeks.
  • You must have iron deficiency anemia, which means your blood does not have enough iron and your hemoglobin (a protein in red blood cells that carries oxygen) level is below 12.0 grams per deciliter if you are a woman or below 13.0 grams per deciliter if you are a man. Alternatively, you must have received treatment with at least 250 milligrams of intravenous iron (iron given directly into a vein) or at least one red blood cell transfusion (receiving blood from a donor) within the past 24 weeks.
  • You must agree not to have procedures or surgeries to treat the small blood vessel spots in your nose or nosebleeds during the main part of the study, except in emergency situations. You must also agree not to start any new treatments for bleeding during this time. Simple nasal packing is allowed.
  • You must be able to understand the study requirements and be willing to follow them, including keeping a daily diary to record your nosebleeds for at least one week before the study begins. You must also be willing to sign a form showing you agree to participate.

Who cannot join the trial?

9 criteria

  • You cannot participate if you are pregnant or breastfeeding, which means nursing a baby with breast milk
  • You cannot participate if you have severe liver disease, meaning serious problems with how your liver works
  • You cannot participate if you have severe kidney disease, meaning serious problems with how your kidneys filter waste from your blood
  • You cannot participate if you have had a recent major surgery or bleeding event that required hospitalization within the past 3 months
  • You cannot participate if you are taking certain medications that affect blood clotting, such as anticoagulants, which are medicines that thin your blood to prevent clots
  • You cannot participate if you have an active infection that requires treatment with antibiotics or other medications
  • You cannot participate if you have a history of severe allergic reactions, meaning very serious reactions where your body responds badly to certain substances
  • You cannot participate if you have received another investigational drug, which means an experimental medicine being tested in research, within the past 30 days
  • You cannot participate if you have any condition that, in the doctor's opinion, would make it unsafe for you to join the study
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Investigated drugs

  • ALN-6400

    is an investigational medication being studied for the treatment of Hereditary Hemorrhagic Telangiectasia (HHT), a genetic disorder that affects blood vessels. This medication is given as an injection and is designed to help manage the symptoms and complications associated with HHT. In this study, researchers are testing different doses of ALN-6400 to see how safe it is, how well patients tolerate it, and whether it can effectively treat the condition.

  • Placebo

    is an inactive substance that looks like the real medication but contains no active treatment. It is used in this study to compare against ALN-6400 to help determine if the actual medication is working better than no treatment at all.

What is already known about the treatment

ALN-6400 – ALN-6400 is an investigational medication currently being studied in clinical trials for the treatment of Hereditary Hemorrhagic Telangiectasia (HHT), a genetic disorder that causes abnormal blood vessel formation leading to frequent nosebleeds and other bleeding problems. The drug is administered as an injection and is being tested in both single doses in healthy volunteers and multiple doses in patients with HHT to evaluate its safety, tolerability, and effectiveness. While the specific mechanism of action has not been fully disclosed in available trial information, ALN-6400 appears to be designed to target the underlying molecular processes that cause abnormal blood vessel development in HHT patients. This medication is still in early-phase clinical testing (Phase 1/2) and has not yet been approved for general medical use.

Investigated diseases

Hereditary Hemorrhagic Telangiectasia – Hereditary Hemorrhagic Telangiectasia is a genetic disorder that affects blood vessels throughout the body. The condition causes abnormal connections between arteries and veins, which can occur in various organs including the nose, lungs, liver, and brain. People with this disease develop small abnormal blood vessels called telangiectasias on the skin and mucous membranes, which are fragile and prone to bleeding. One of the most common symptoms is frequent nosebleeds that can range from mild to severe. The disease is inherited in families and symptoms typically worsen with age. The abnormal blood vessels can also form larger connections called arteriovenous malformations in internal organs, leading to various complications depending on their location.
Trial detailsLast updated 7 Oct 2026
Age18+ yearsPhasePhase ITrial ID2025-522510-23-00Protocol codeALN-6400-001Estimated enrolment48 patientsSponsorAlnylam Pharmaceuticals Inc.

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