In the KYSA-6 clinical trial, doctors are looking at a type of treatment called Chimeric Antigen Receptor (CAR) T-cell therapy in people with generalized , who do not get better with standard therapies.
The goal of this trial is to find out how safe and effective CAR T-cell therapy is in people living with generalized myasthenia gravis. Kyverna has developed the investigational CAR T-cell therapy, KYV-101, for generalized myasthenia gravis. KYV-101 will be administered in the KYSA-6 clinical trial.
In the KYSA-6 clinical trial, participants’ T cells (a type of immune cell that helps to protect from diseases) will be collected, modified, and returned to the body so they can target and remove B cells (another type of immune cell) that, when unhealthy, can increase inflammation and may contribute to the symptoms of myasthenia gravis.
What is myasthenia gravis?
Definition: Myasthenia gravis is a neuromuscular autoimmune disease that can impact the function of muscles throughout the body. There are two clinically recognized forms of myasthenia gravis: ocular and generalized myasthenia gravis. In ocular myasthenia gravis, muscles that control the movement of the eyes and/or eyelids are impacted. In generalized myasthenia gravis, varying combinations of muscles of the eyes/eyelids, arms, legs, and respiratory system may be impacted.
Who it affects: Myasthenia gravis can affect anyone but is more common in women under the age of 40 and men over the age of 60. Individuals with myasthenia gravis generally experience muscle weakness and fatigue, with a range of symptoms including shortness of breath, difficulty swallowing, weakness of the eye muscles and limbs, impaired speech, and respiratory failure.
Traditional treatments: Myasthenia gravis can be treated with a variety of therapies including intravenous , plasma exchange, , as well as newer treatments targeting B cells, complement inhibition, and neonatal Fc receptor inhibition. Treatment goals are to prevent disability, increase survival, prevent treatment-related adverse events, and improve quality of life. Up to 15% of patients continue to have disability due to insufficient control of clinical symptoms and unresolved side effects.
What is CAR T-cell therapy?
CAR T-cell therapy is a type of treatment called . 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.
CAR T-cell therapies have advanced in recent years. Doctors are now exploring if new CAR T-cell therapies can treat autoimmune diseases.
CAR T-cell therapy is not yet approved for people with myasthenia gravis.
Step 1 ‘Apheresis’
First, blood is collected from the patient and is filtered by a machine in a process called . In this process, white blood cells (including T cells) are separated from blood.
Step 2 ‘Alter T cells’
T cells are altered in the laboratory so the cells can recognize and remove 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 ‘Target B cells’
The CAR T cells target and remove 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 healthy B cells.
Who can take part in the KYSA-6 clinical trial?
You may be able to participate in the KYSA-6 trial if:
You are between ages 18 and 75.
You have been diagnosed with class IIB–IV generalized myasthenia gravis.
Your disease is active as defined in the trial protocol and you have tried previous treatments but you did not get better.
If you are interested in taking part in the trial, your doctor can refer you to a trial site. The trial doctor will ask some questions to see if you can take part. This may include performing additional tests. The trial doctor will also explain the detailed criteria for participating. This trial has multiple sites in the United States. You may need to travel if you do not live near a trial site.
Participant Accommodations
We aim to make every participant’s KYSA-6 clinical trial experience as easy as possible. Accommodations for trial participation may be available and may include travel and caregiver support.
What will happen in the KYSA-6 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:
During the screening period, you will undergo various study eligibility assessments. If you choose to take part in the trial, you will be asked to provide written informed consent.
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 and made into CAR T cells.
About 1 week before administering KYV-101, you will receive pre-dosing 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 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.
CAR T-cell therapies are associated with and immune effector cell-associated , which may be potentially serious or life-threatening but generally resolve within the first month after treatment.
Symptoms of CRS include fever, nausea, feeling tired (fatigue), and body aches and can progress in severity and may include low blood pressure, high fever, shock, and potentially organ failure.
Symptoms of ICANS include fatigue, uncontrolled movements (tremors), impairment in thinking, loss of speech, muscle weakness, or more severe symptoms such as 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.
Resources
KYSA-6 Flyer
Information about the KYSA-6 clinical trial to discuss with your healthcare provider.
Patient advocacy groups can offer additional educational resources.
Check out these patient advocacy groups for more information. Note that these links are provided for informational purposes only and its content is not necessarily supported or endorsed by Kyverna Therapeutics.
Contact
For more information, please contact Kyverna by completing the form.
Frequently Asked Questions
The KYSA-6 clinical trial aims to learn more about KYV-101, a CAR T-cell therapy, as a potential treatment for people living with myasthenia gravis.
The KYSA-6 clinical trial is sponsored by Kyverna Therapeutics, a company dedicated to developing therapies to help reset the immune system and help eliminate the need for long-term or suboptimal therapies.
Clinical trials are research studies that look to find better ways to prevent, diagnose, or treat disease. In a Phase 1 clinical trial, doctors want to understand if a treatment is safe and well tolerated in humans. Phase 1 trials are the first stage of human clinical trials and usually involve only a small number of people. Phase 2 clinical trials expand the study to a larger group of individuals to assess the treatment’s effectiveness and further evaluate its safety.
To ensure that clinical trials are conducted safely, doctors take safety precautions which include:
Informed consent: Participation in the trials is voluntary. Participants in a clinical trial are to provide informed consent before they can participate in the study. This means that participants will be given information about the clinical trial, including the risks and benefits, before the participants indicate if they want to join the study.
Data safety monitoring: An independent data safety monitoring board (DSMB) is a group of independent experts who review the data collected in a clinical trial on a regular basis. The DSMB is responsible for ensuring that the clinical trial is being conducted safely and that the participants are not being put at risk.
Side effect reporting: All side effects that occur in a clinical trial must be reported to the clinical trial team. An adverse event is any unwanted or unexpected medical occurrence that happens to a participant during a clinical trial.
Withdrawal from the clinical trial: Participants in a clinical trial have the right to withdraw at any time.
No. All participants will receive KYV-101 and will be closely monitored by a team of healthcare professionals.
To protect your privacy, steps taken by the clinical trial team will include:
Use of codes or pseudonyms instead of your real name.
Secure storage of your data without access by unauthorized individuals.
Requiring clinical trial investigators to sign confidentiality agreements.
You will also have the right to withdraw from the study at any time. Data that was collected by your study doctor will still be able to be used by the sponsor.
Myasthenia gravis is a rare disease, it affects up to 200 individuals per every million worldwide.
Myasthenia gravis results from the production of antibodies directed against the connection between nerves and muscles. It is not known what causes this process to begin, but the body’s immune system appears to play a role.
This is the first study using KYV-101 in humans with myasthenia gravis, but KYV-101 has been used to treat individuals with myasthenia gravis under a form of compassionate-use treatment permitted in Germany. It is also being investigated in individuals with lupus nephritis, systemic sclerosis (scleroderma), multiple sclerosis, and stiff-person syndrome.
