What Is Ziltivekimab?
Ziltivekimab is an investigational drug that is not yet approved for market. It is a monoclonal antibody designed to target interleukin-6 (IL-6). IL-6 is a protein in the body that plays a key role in inflammation and is involved in various disease processes. By targeting IL-6, ziltivekimab aims to reduce inflammation and its associated effects.
This medication is currently being studied in clinical trials for its potential to treat several serious conditions. Researchers are investigating whether ziltivekimab can help reduce atherosclerotic plaque in the blood vessels of the heart, manage overall cardiovascular risk, and treat people who have been hospitalized due to a heart attack. It is also being explored as a treatment for participants living with heart failure and inflammation, and for those with chronic kidney disease. Ziltivekimab is typically administered as a subcutaneous injection, meaning it is given under the skin, usually once per month.
Uses and Conditions Under Study
Ziltivekimab has been studied in 11 clinical trials involving a total of 23,775 participants. The first trial began in 2019, with the latest expected to conclude in 2025.
Ziltivekimab is primarily being investigated for conditions related to inflammation and cardiovascular health. Inflammation is a key factor in many heart-related diseases. Studies are exploring its role in reducing atherosclerotic plaque, which is the buildup of fatty deposits in arteries, and in managing overall cardiovascular risk. It is also being studied for acute myocardial infarction (AMI), commonly known as a heart attack, with the goal of preventing future heart attacks or strokes. These areas are covered in multiple trials, including 4 trials for inflammation, 3 trials for cardiovascular risk, and 2 trials for AMI.
Another area of focus is heart failure, a condition where the heart cannot pump enough blood to meet the body's needs. Ziltivekimab is being studied in 2 trials to see if it can help treat participants living with heart failure, particularly when inflammation is also present.
Chronic kidney disease (CKD) is also being investigated. This condition involves a gradual loss of kidney function over time. Ziltivekimab is being studied in 2 trials for its potential benefits in this patient population.
One trial also included healthy participants to understand how the drug is absorbed, distributed, metabolized, and eliminated by the body. Clinical trials for ziltivekimab are primarily sponsored by Novo Nordisk A/S, which is involved in 9 trials. Other sponsors include Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) and ECRI bv.
Dosing
Ziltivekimab is administered as a subcutaneous injection, meaning it is given under the skin. This medication has been studied using different delivery methods, including both pre-filled syringes and pen-injectors, to assess ease of use and drug delivery.
The typical dosing schedule for ziltivekimab in clinical trials involves administration once per month. Some studies have explored an initial loading dose followed by a maintenance dose to achieve desired drug levels. Treatment duration can extend for up to 4 years in some ongoing trials.
Clinical trials have investigated several dose strengths to determine the most effective and safest amount. These include 7.5 mg, 15 mg, and 30 mg of ziltivekimab. Researchers are also examining how quickly and to what extent different compositions of ziltivekimab are absorbed, transported, and eliminated from the body to optimize future dosing recommendations.
Side Effects
In clinical trials, patients taking Ziltivekimab experienced certain side effects more often than those taking a placebo. In a smaller study group (n=23), 8.7% of patients on Ziltivekimab had increased blood bilirubin levels and 8.7% experienced eosinophilia (an increase in a type of white blood cell), compared to 0% for both on placebo.
From larger studies (n=196-219), the most common side effects that occurred more frequently with Ziltivekimab compared to placebo included:
- Hypertension (high blood pressure): 5.6% of patients taking Ziltivekimab experienced this, compared to 3.1% on placebo.
- Dizziness: 5.1% on Ziltivekimab, compared to 1.5% on placebo.
- Nasopharyngitis (common cold): 4.6% on Ziltivekimab, compared to 2.6% on placebo.
- Oedema peripheral (swelling in the limbs): 4.6% on Ziltivekimab, compared to 3.1% on placebo.
- Arthralgia (joint pain): 3.6% on Ziltivekimab, compared to 1.5% on placebo.
Other side effects, such as urinary tract infection (5.1% on Ziltivekimab vs 6.2% on placebo), diarrhea (3.2% on Ziltivekimab vs 7.8% on placebo), and cough (3.2% on Ziltivekimab vs 6.5% on placebo), were reported less frequently in patients taking Ziltivekimab compared to placebo.
Clinical Trial Results
Ziltivekimab has been studied in patients with advanced chronic renal disease to evaluate its effect on inflammation and other markers. Results from two completed trials are summarized below.
Study NCT03926117
This trial investigated the reduction of inflammation. Key findings included:
- Inflammation Markers: Patients treated with Ziltivekimab showed significant reductions in inflammation. High-sensitivity C-reactive protein (Hs-CRP) levels decreased by 88.12% with 15 mg of Ziltivekimab, by 91.64% with 30 mg, and by 76.57% with 7.5 mg, compared to a 4.49% decrease in the placebo group. Fibrinogen levels also decreased by 24.69% (15 mg), 37.17% (30 mg), and 25.20% (7.5 mg) with Ziltivekimab, versus a 1.62% decrease with placebo.
- Bilirubin Levels: Ziltivekimab was associated with an increase in bilirubin levels. For example, the 15 mg dose led to a mean increase of 9.2 milligrams per deciliter (mg/dL) and the 7.5 mg dose led to an 8.9 mg/dL increase, while the placebo group saw a mean decrease of 0.007 mg/dL.
- Blood Pressure: Diastolic blood pressure (DBP) increased by 3.1 mmHg in the 30 mg Ziltivekimab group and by 2.9 mmHg in the 7.5 mg group, compared to a 0.7 mmHg increase in the placebo group.
- Anti-drug Antibodies (ADAs): Anti-drug antibodies were detected in 7.6% of patients on 15 mg Ziltivekimab, 10.8% on 30 mg, and 6.2% on 7.5 mg, compared to 0% in the placebo group.
Study NCT04626505 (Japan)
This trial, conducted in Japan, also focused on inflammation reduction in patients with advanced chronic renal disease:
- Inflammation Markers: Similar to the other study, Ziltivekimab led to substantial reductions in Hs-CRP levels. The 15 mg dose resulted in a 96.23% decrease and the 30 mg dose a 93.41% decrease, compared to a 27.01% decrease in the placebo group.
- Kidney Function Marker: Patients receiving 30 mg of Ziltivekimab experienced a mean reduction of 382.3 grams per kilogram (g/kg) in protein creatinine ratio, and those on 15 mg saw a reduction of 148.9 g/kg. In contrast, the placebo group had a mean increase of 412.3 g/kg. A reduction in protein creatinine ratio can indicate improved kidney function.
- Anti-drug Antibodies (ADAs): No participants in either the 15 mg or 30 mg Ziltivekimab groups developed anti-drug antibodies in this study.
- Adverse Events: There were 25 treatment-emergent adverse events (TEAEs) in the placebo group, 41 in the 15 mg Ziltivekimab group, and 16 in the 30 mg Ziltivekimab group. Serious adverse events (SAEs) occurred in 2 instances in the placebo group and 5 instances in the 15 mg Ziltivekimab group, with 0 in the 30 mg Ziltivekimab group. No participants discontinued the study drug due to adverse events in any group.
Currently Recruiting Trials
Ziltivekimab is currently being investigated in several clinical trials for its potential to treat various heart-related conditions. These studies aim to understand how this investigational medicine might help patients who have experienced a heart attack or are living with heart failure and inflammation.
- A Phase 3 study, NCT07276282, sponsored by ECRI bv, is examining the effects of Ziltivekimab on coronary atherosclerotic burden in patients who have had an acute myocardial infarction. This study is recruiting approximately 332 participants to explore how Ziltivekimab might impact coronary artery disease and atherosclerosis.
- Another Phase 3 study, NCT07301034, sponsored by Novo Nordisk A/S, is looking at the effect of Ziltivekimab on plaque in the heart's blood vessels in people who have experienced a heart attack. This research aims to determine if Ziltivekimab can effectively reduce atherosclerotic plaque, with a target enrollment of 332 participants.
- The ARTEMIS study, NCT06118281, is a large Phase 3 research study sponsored by Novo Nordisk A/S. It is designed to evaluate how Ziltivekimab works compared to a placebo in people admitted to the hospital due to a heart attack. This study seeks to enroll 10,000 participants to see if Ziltivekimab can reduce the development of heart disease and prevent future heart attacks or strokes.
- A smaller Phase 3 trial, NCT06263244, sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), is focused on specifying the anti-inflammatory effects of Ziltivekimab. This study is recruiting 40 participants with atherosclerosis and inflammation to assess whether Ziltivekimab therapy reduces arterial wall inflammation and systemic inflammatory tone.
- For patients with heart failure and inflammation, Novo Nordisk A/S is sponsoring two Phase 3 studies. The first, NCT06200207, is investigating how Ziltivekimab works compared to a placebo in 680 participants.
- The second, NCT05636176, is a larger study for people living with heart failure and inflammation, aiming to enroll 5,600 participants. Both studies will compare Ziltivekimab to a placebo to see if it can be an effective treatment.
Where to Participate
Ziltivekimab clinical trials are widely accessible, with recruiting sites across the United States. There are currently 336 sites in 239 cities across 47 states where you might be able to participate. Some of the cities with the most active recruiting sites include:
- Houston, Texas (12 sites)
- New York, New York (7 sites)
- San Antonio, Texas (6 sites)
- Jacksonville, Florida (6 sites)
- Richmond, Virginia (6 sites)
- Seattle, Washington (5 sites)
- Dallas, Texas (5 sites)
- Louisville, Kentucky (5 sites)
- Los Angeles, California (5 sites)
- Overland Park, Kansas (4 sites)
To be eligible for these studies, participants must generally be between 18 and 85 years of age. All genders are welcome, but healthy volunteers and children are not being recruited for these specific Ziltivekimab trials.
Development Timeline
The development journey for Ziltivekimab began on April 24, 2019, with its first clinical trial. Since then, a total of 11 trials have been initiated, involving 23,775 participants. The majority of these studies, seven, are currently in Phase 3, the final stage before potential regulatory approval. Earlier phases included two Phase 1 and two Phase 2 trials.
Novo Nordisk A/S has been the primary driver of Ziltivekimab's development, sponsoring nine of the trials. Other organizations, ECRI bv and Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), have also contributed to the research efforts.
The scope of Ziltivekimab's investigation has evolved significantly over time. Initial studies explored conditions like IBS-C and hyperphosphatemia. However, the focus has expanded to primarily address cardiovascular and inflammatory conditions. The pipeline now includes studies for Heart Failure, Chronic Kidney Disease, Acute Myocardial Infarction (AMI), Coronary Atherosclerosis of Native Coronary Artery, Myocardial Infarction, Systemic Inflammation, Atherosclerosis, and Coronary Artery Disease. The latest trial is projected to conclude on December 24, 2025, marking a significant milestone in its development.