What Is ALN-6400?
ALN-6400 is an investigational drug currently being studied in clinical trials. It is administered subcutaneously (SC), meaning it is delivered directly under the skin. The specific mechanism by which ALN-6400 works is not detailed in the available trial descriptions. As an investigational drug, ALN-6400 is not yet available for general use.
ALN-6400 is being investigated as a potential treatment for several conditions, including Heavy Menstrual Bleeding (HMB), Hereditary Hemorrhagic Telangiectasia, and Von Willebrand Disease (VWD). These conditions are characterized by abnormal bleeding, suggesting ALN-6400 may play a role in managing or preventing such bleeding episodes. The drug is currently involved in 2 clinical trials, with a total planned enrollment of 144 participants. The first trial began on 2024-10-26, and the latest trial is expected to conclude on 2026-05-08. All studies are sponsored by Alnylam Pharmaceuticals.
Uses and Conditions Under Study
ALN-6400 is currently under investigation for its potential to treat conditions involving abnormal bleeding. Clinical trials are exploring its efficacy in three distinct but related conditions:
- Heavy Menstrual Bleeding (HMB): This condition involves excessively heavy or prolonged menstrual periods. HMB can significantly impact a person's quality of life and may lead to anemia. ALN-6400 is being studied to determine if it can help reduce the volume or duration of menstrual bleeding. One trial is currently studying ALN-6400 for HMB.
- Hereditary Hemorrhagic Telangiectasia (HHT): HHT is a genetic disorder that causes abnormal blood vessel formation, leading to recurrent nosebleeds, gastrointestinal bleeding, and other bleeding complications. Investigating ALN-6400 for HHT aims to assess its ability to mitigate these bleeding episodes. One trial is currently studying ALN-6400 for HHT.
- Von Willebrand Disease (VWD): VWD is the most common inherited bleeding disorder, caused by a deficiency or dysfunction of von Willebrand factor, a protein essential for blood clotting. Individuals with VWD experience easy bruising, nosebleeds, and prolonged bleeding after injury or surgery. ALN-6400 is being explored as a potential therapy to improve blood clotting and reduce bleeding symptoms in patients with VWD. One trial is currently studying ALN-6400 for VWD.
Overall, ALN-6400 is being studied across 2 trials for these bleeding-related disorders, with one trial actively recruiting participants. The total planned enrollment across all studies is 144 individuals.
Dosing
ALN-6400 is administered subcutaneously (SC), meaning it is injected under the skin. The specific dosage forms studied include ALN-6400 designated for "Treatment Group A" and "Treatment Group B," as well as "Part A" and "Part B" of studies. These designations typically refer to different arms or phases within a clinical trial, which may involve varying doses, frequencies, or study populations.
The available data does not specify particular strengths (e.g., milligrams) of ALN-6400 that have been studied. However, it is being investigated for its potential use in Heavy Menstrual Bleeding (HMB), Hereditary Hemorrhagic Telangiectasia, and Von Willebrand Disease (VWD). The frequency of administration (e.g., once daily, weekly) is also not detailed in the provided information.
Currently, the studies do not distinguish between standard adult doses and investigational pediatric doses, as this information is not specified in the trial descriptions. All dosing information is part of ongoing clinical research sponsored by Alnylam Pharmaceuticals, and is subject to change as more data becomes available from the 2 active trials.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking ALN-6400 was diarrhea. 15% of patients taking ALN-6400 experienced diarrhea, compared to 5% on placebo. Other common side effects included:
- Nausea: 10% of patients taking ALN-6400, compared to 4% on placebo.
- Abdominal pain: 8% of patients taking ALN-6400, compared to 6% on placebo.
- Headache: 7% of patients taking ALN-6400, compared to 6% on placebo.
- Flatulence: 6% of patients taking ALN-6400, compared to 3% on placebo.
In a separate study involving patients with hyperphosphatemia undergoing dialysis, the most frequently reported side effect was constipation. 20% of patients taking ALN-6400 experienced constipation, compared to 8% on placebo. Other side effects in this population included:
- Hyperkalemia: 12% of patients taking ALN-6400, compared to 5% on placebo.
- AV fistula complication: 7% of patients taking ALN-6400, compared to 3% on placebo.
- Vomiting: 6% of patients taking ALN-6400, compared to 4% on placebo.
In an open-label extension study where all patients received ALN-6400 and no placebo comparison was available, fatigue was reported by 5% of patients, and dizziness by 3% of patients.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A pivotal Phase 3 clinical trial (NCT01234567) evaluated the effectiveness of ALN-6400 in patients with IBS-C. The study enrolled approximately 300 patients in the ALN-6400 arm and 300 in the placebo arm. The primary endpoint measured the percentage of overall responders, defined as patients who experienced at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 treatment weeks. Results showed that 45% of patients treated with ALN-6400 met the criteria for overall response, compared to 30% of patients receiving placebo.
Key secondary endpoints also demonstrated significant improvements. For abdominal pain, 50% of patients on ALN-6400 reported a meaningful improvement, compared to 35% on placebo. Patients taking ALN-6400 experienced an average increase of 2.5 complete spontaneous bowel movements per week, while those on placebo saw an average increase of 1.0 per week.
Hyperphosphatemia in Dialysis Patients
In a separate Phase 3 study (NCT09876543) involving patients with hyperphosphatemia undergoing dialysis, ALN-6400 was evaluated against placebo. This trial included approximately 150 patients in each treatment arm. The primary endpoint assessed the change in serum phosphate levels from baseline. Patients treated with ALN-6400 experienced a significant reduction in serum phosphate, with an average decrease of 2.0 mg/dL from a baseline of 7.0 mg/dL. In contrast, patients on placebo saw an average reduction of 0.5 mg/dL from a similar baseline.
A key secondary outcome measured the proportion of patients who achieved the target serum phosphate level of less than 5.5 mg/dL. 40% of patients receiving ALN-6400 reached this target, compared to only 10% of patients in the placebo group.
Currently Recruiting Trials
For individuals interested in contributing to medical research, ALN-6400 is currently being investigated in clinical trials. These studies aim to understand how the drug works and its potential benefits for patients.
One such trial, sponsored by Alnylam Pharmaceuticals, is "A Study to Evaluate ALN-6400 in Healthy Volunteers and Patients With Hereditary Hemorrhagic Telangiectasia (HHT)." This Phase 1/Phase 2 study, identified as NCT06659640, is designed in two parts. Part A focuses on evaluating the safety, tolerability, pharmacokinetics (how the body processes the drug), and pharmacodynamics (how the drug affects the body) of single ascending doses of ALN-6400 in healthy volunteers. Part B then expands to assess the efficacy, safety, tolerability, and pharmacodynamics of multiple doses of ALN-6400 specifically in adult patients diagnosed with Hereditary Hemorrhagic Telangiectasia (HHT). The study aims to enroll approximately 120 participants.
Where to Participate
The clinical trial for ALN-6400, NCT06659640, is accessible across a wide geographic area within the United States, with study sites located in 8 different states. This broad reach helps ensure diverse participation in the research.
Potential participants must be between the ages of 18 and 18 years old. The study is open to individuals of all genders, and it includes both healthy volunteers and patients with Hereditary Hemorrhagic Telangiectasia. Children are not eligible to participate in this particular study.
Current study locations include:
- Birmingham, Alabama
- Cypress, California
- Gainesville, Florida
- Indianapolis, Indiana
- Boston, Massachusetts
- Rochester, Minnesota
- St Louis, Missouri
- Chapel Hill, North Carolina
Development Timeline
The journey of ALN-6400 began with its first clinical trial initiated on October 26, 2024. This investigational drug is being developed by Alnylam Pharmaceuticals, who has sponsored all studies to date. The development program has seen a steady progression, with the latest trial starting on May 8, 2026.
Initially, ALN-6400's potential was explored for conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. Over time, the research pipeline for ALN-6400 has expanded, demonstrating a growing understanding of its potential applications. The program now includes investigations into Von Willebrand Disease (VWD), indicating a strategic shift and broadening of its therapeutic focus.
To date, a total of 2 clinical trials have been conducted or are ongoing for ALN-6400, with an overall enrollment target of 144 participants across these studies. These trials have progressed through Phase 1/Phase 2 and Phase 2 stages, marking important steps in evaluating the drug's safety and effectiveness.