First, blood is collected from the patient and is filtered by a machine in a process called apheresis.
In this process, white blood cells (including T cells) are separated from blood.
The KYSA-1
clinical trial is enrolling!
Exploring new medicines to help
treat patients with Lupus Nephritis
What is the KYSA-1 clinical trial?
In the KYSA-1 clinical trial, researchers are looking at a type of treatment called CAR T-cell therapy in people with active lupus nephritis who do not get better with standard therapies.
Researchers want to find out how safe CAR T-cell therapy is in people living with lupus nephritis.
Kyverna, along with the NIH, have developed the CAR T-cell therapy, KYV-101, for lupus nephritis. This is the treatment that will be used in the KYSA-1 clinical trial.
In the KYSA-1 clinical trial, participants’ T cells (a type of white blood cell that helps to protect from diseases) will be collected, modified, and returned to the body so they can attack B cells (a type of immune cell that can increase inflammation and the symptoms of lupus nephritis).
What is a clinical trial?
Clinical trials are research studies that look to find better ways to prevent, diagnose, or treat disease.
In a Phase I clinical trial, researchers want to understand if a treatment is safe and well tolerated in humans.
Phase I trials are the first stage of human clinical trials and usually involve only a small number of people.
Phase I trials typically aim to find out:
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How much of a treatment is safe to give.
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Which side effects are likely.
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What happens to the treatment in the body.
What is systemic lupus erythematosus and lupus nephritis?
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Systemic lupus erythematosus (SLE), or lupus for short, causes inflammation in various body organs because the immune system is abnormally active. It commonly affects the skin, joints, and internal organs such as the kidneys and can lead to fatigue, skin rashes, aching joint and other symptoms.
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Lupus nephritis is a serious kidney manifestation of SLE which over time, if not well treated, can lead to kidney failure (where the kidneys cannot function on their own).
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Researchers categorize lupus nephritis into different classes based on how much of the kidney is involved (Class I to VI) which can guide treatments. Lupus nephritis is typically treated with various medications, such as corticosteroids and other immune suppressive therapies.
What is CAR T-cell therapy?
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CAR T-cell therapy is a type of treatment called immunotherapy. This means it works with your immune system to target the cells that harm your body. This type of therapy was discovered more than 20 years ago and is now used to treat people with certain types of cancer.
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Different CAR T-cell therapies treat different cancers, such as leukemia, multiple myeloma, and B-cell non-Hodgkin lymphoma.
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CAR T-cell therapies have advanced in recent years. Researchers are now exploring if new CAR T-cell therapies can treat autoimmune diseases.
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CAR T-cell therapy is not yet approved for people with lupus nephritis.
How it works
Step 1 ‘Apheresis’
Step 2 ‘Alter T cells’
Researchers alter the T cells in the laboratory so the cells can recognize, attack, and destroy the B cells.
Step 3 ‘Infusion’
Doctors then return the patient’s own altered T cells back to them through an infusion directly into their veins (intravenous (IV) infusion).
Step 4 ‘Attack B cells’
The CAR T cells attack B cells, including unhealthy B cells with the goal of helping to control, reduce, or reverse the disease.
Step 5 ‘Replenish B cells’
The aim is for the body to replenish with its own healthy B cells.
What will happen in the KYSA-1 clinical trial?
If you are selected to participate, one of the doctors running the trial (or someone on their behalf) will talk with you about what you can expect as a participant in the trial so that you understand and are comfortable with what it means to take part. This is called informed consent. If you are able to enroll in the trial, these are the key steps you will be involved in:
Serious and potentially life-threatening side effects can occur from CAR T-cell therapy including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) and typically resolve within the first month after treatment.
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CRS happens when your body responds too aggressively to an infusion of CAR T-cell therapy. Mild symptoms may include fever, nausea, feeling tired (fatigue), and body aches. Symptoms can progress in severity and may include high blood pressure and high fever, shock, and potentially organ failure.
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ICANS affects the nervous system and can cause symptoms such as fatigue, uncontrolled movements (tremors), impairment in thinking, loss of speech, muscle weakness, seizures, and swelling in the brain.
People receiving this treatment are always in the care of a doctor, who monitors them closely for these side effects and can treat their symptoms to help prevent their worsening.
- During the screening period, you will undergo various study eligibility assessments and be required to provide written informed consent if you choose to take part in the trial.
- During apheresis, white blood cells will be collected through an intravenous (IV) line, and T cells are removed.
- The other cells will be returned to the body.
- The process usually takes about 2-3 hours.
- After your blood collection for apheresis, you may return home.
- After apheresis and during the manufacturing process, the collected T cells will be altered by researchers and made into CAR T cells.
- About 1 week before administering KYV-101, you will receive pre-dosing lymphodepletion therapy. This therapy will help to prepare your body for the new CAR T cells.
- During the pre-dosing phase you will need to be in person at the trial site.
- The KYV-101 CAR T cells are returned to your body, delivered in a single infusion directly into your vein (intravenous (IV) infusion).
- Beginning with KYV-101 infusion, you will be required to stay in the hospital (inpatient) at the trial site for 10 days. This is so doctors can check how well you are responding to treatment and monitor any potential side effects that you may have like fever, fatigue, confusion, or tremors.
- After leaving the hospital, you will need to stay close to the trial site (within 1 hour) for 2 weeks. You will need to be accompanied by another adult who can help to support you following the treatment.
- You will need to return to the trial site periodically for follow-up visits to have your health monitored for up to 24 months after KYV-101 infusion.
- You will be asked to take part in a separate long-term follow-up study so that you can be monitored for side effects.
Pronunciations
Pronunciations
- Lupus nephritis (LOO-pus nuh-FRY-tuhs)
- Systemic lupus erythematosus (sis-TEH-mik LOO-pus AYR-ih-THEE-muh-TOH-sus)
- Immunotherapy (IH-myoo-noh-THAYR-uh-pee)
- Leukemia (loo-KEE-mee-uh)
- Multiple myeloma (MY-eh-LOH-muh)
- B-cell non-Hodgkin lymphoma (non-HOJ-kin lim-FOH-muh).
- Apheresis (a-feh-REE-sis)
- Intravenous infusion (IN-truh-VEE-nus in-FYOO-zhun)
- Cytokine release syndrome (SY-toh-kine reh-LEES SIN-drome)
- Neurotoxicity (NOOR-oh-tok-SIH-sih-tee)
- Lymphodepletion (LIMF-o-di-PLEE-shuhn)
