Stiff-Person SyndromePhase 2NCT06588491
KYSA-8: A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Treatment Refractory Stiff Person Syndrome
A Phase 2 study testing Standard lymphodepletion regimen in people with Stiff-Person Syndrome and SPS, run by Kyverna Therapeutics at 3 sites in United States.
Trial summary
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Subjects with Treatment Refractory Stiff Person Syndrome Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Stiff-Person Syndrome, SPS
- What is being tested?
- Standard lymphodepletion regimen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 3 sitesUnited States
- Study dates
- 25 Sep 2024to 25 Jun 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must have been diagnosed SPS per the following criteria:
- Rigidity of limb and axial (trunk) muscles prominent in the abdominal and thoracolumbar paraspinal areas and making bending difficult
- Clinical or electrophysiological evidence of continuous contraction of agonist and antagonist muscles
- Episodic spasms precipitated by unexpected noises, tactile stimuli, or emotional upset
- Absence of any other neurologic disease that could explain the stiffness and rigidity
- High titer serum anti-GAD65 antibodies shown at screening -OR- seropositive for anti-glycine antibodies. If anti-GAD65 antibodies are lower than the high titer threshold peripherally but positive in the cerebrospinal fluid (CSF), the subject can be included. A prior documented high titer anti-GAD65 antibody level may be acceptable subject to sponsor review.
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- Active symptoms with inadequate response to at least one immunomodulatory therapy.
- Stiffness index ≥2.
- At least 20 of the 25 enrolled subjects should be ambulatory.
Who cannot join
- Bedridden subjects for more than 3 months.
- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-SPS progressive neurologic condition or progressive multifocal leukoencephalopathy (PML).
- History of stroke, seizure, dementia, Parkinson's disease, cerebellar diseases, psychosis, aphasia, and any other neurologic disorder that is of a nature and severity that the investigator considers would increase the risk for the subject.
- Cardiac ejection fraction ≤ 40%.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: KYSA-8: A Phase 2 Open-Label, Single-Arm, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Treatment Refractory Stiff Person Syndrome
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Subjects with Treatment Refractory Stiff Person Syndrome
Read the detailed description
Stiff person syndrome (SPS) is a rare progressive immune-mediated disorder of the central nervous system (CNS) that is characterized by progressive rigidity and painful spasms of predominantly axial and proximal limb muscles. The condition gradually worsens over time and left untreated, it can lead to permanent disability and in some cases, mortality.
B cells contribute to systemic autoimmunity and development of disease in several ways, most notably via cytokine production, antigen presentation and complement activation (via autoantibody production). In SPS, B cell involvement is supported by the presence of antibodies against glutamic acid decarboxylase (GAD), which is widely expressed within the CNS, catalyzing the conversion of the excitatory neurotransmitter l-glutamate to the inhibitory GABA.
CAR-T therapy such as KYV-101 may be an effective treatment for SPS, by targeting these autoreactive B cells. Using chimeric antigen receptor (CAR) T-cell technology, engineered T cells with receptors are designed to recognize and eliminate B cells, including those that produce GAD autoantibodies. This approach aims to intervene at the root of the autoimmune response, offering a precise and potentially transformative treatment for SPS. CAR-T cell therapy holds promise as a targeted and effective intervention, addressing the autoimmune component directly and potentially halting disease progression.
- Conditions
- Stiff-Person Syndrome, SPS
- Being tested
- Standard lymphodepletion regimen
- Keywords
- SPS, Stiff-Person Syndrome
- Medical subject headings
- Stiff-Person Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard lymphodepletion regimenBiological
Also called Cyclophosphamide, Fludarabine
Standard lymphodepletion regimen
| Study group | Role | What they receive |
|---|---|---|
| KYV-101 CAR-T cells with lymphodepletion conditioning | Experimental | Dosing with KYV-101 CAR T cells Receives: Biological: Standard lymphodepletion regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate efficacy of KYV-101
Change in the Timed 25-Foot Walk (T25-FW) from baseline
Measured: Up to 12 months
To evaluate the safety of KYV-101
Incidence of adverse events and laboratory abnormalities
Measured: Up to 12 months
Secondary outcomes (4)
To evaluate efficacy of KYV-101
Change in Modified Rankin Scale from baseline Modified Rankin Scale: Scoring is from 0 (no symptoms) to 6 (death). A higher score indicates a worse outcome.
Measured: Up to 12 months
To evaluate efficacy of KYV-101
Change in the scores of the distribution-of-stiffness index from baseline. Distribution of Stiffness Index: Scoring is from 0 to 6. A higher score indicates a worse outcome.
Measured: Up to 12 months
To evaluate efficacy of KYV-101
Change in Hauser Ambulation Index. Hauser Ambulation Index: Scoring is from 0 to 9. A higher score indicates a worse outcome.
Measured: Up to 12 months
To evaluate efficacy of KYV-101
Change in Heightened sensitivity scale. Heightened Sensitivity Scale: Scoring is from 0 to 7. A higher score indicates a worse outcome.
Measured: Up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2024
- Study start25 Sep 2024
- Primary completion25 Jun 2026
- Study completion25 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Stiff-Person SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyverna Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Kyverna Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06588491
- Sponsor's protocol ID
- KYSA-8
- Other IDs
- KYV101-008
- Status last verified
- Jul 2026
- First submitted
- 6 Sep 2024
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Piquet AL, et al. Miv-cel CD19 CAR T-cell therapy shows efficacy and safety in stiff person syndrome in a pivotal, multicenter, phase 2 study (KYSA-8). Presented at: American Academy of Neurology (AAN) Annual Meeting; April 18-21, 2026; Chicago, IL. Late Breaking Science Abstract 008.
Dalakas MC. Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2023 Apr 14;10(3):e200109. doi: 10.1212/NXI.0000000000200109. Print 2023 May.
PubMed 37059468Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-165. doi: 10.1159/000212375. Epub 2009 Apr 6.
PubMed 19349711
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KYSA-8: A Phase 2 Open-Label, Single-Arm, Multicenter Study of KYV-101, an Autologous Fully Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy, in Subjects With Treatment Refractory Stiff Person Syndrome
- ClinicalTrials.gov ID
- NCT06588491
- Acronym / sponsor ID
- KYSA-8
- Conditions
- Stiff-Person Syndrome, SPS
- Keywords
- SPS, Stiff-Person Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Kyverna TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2024 (actual)
- Primary completion
- 25 Jun 2026 (actual)
- Study completion
- 25 Jun 2026 (actual)
- First posted
- 19 Sep 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy for Subjects with Treatment Refractory Stiff Person Syndrome
Detailed description
Stiff person syndrome (SPS) is a rare progressive immune-mediated disorder of the central nervous system (CNS) that is characterized by progressive rigidity and painful spasms of predominantly axial and proximal limb muscles. The condition gradually worsens over time and left untreated, it can lead to permanent disability and in some cases, mortality.
B cells contribute to systemic autoimmunity and development of disease in several ways, most notably via cytokine production, antigen presentation and complement activation (via autoantibody production). In SPS, B cell involvement is supported by the presence of antibodies against glutamic acid decarboxylase (GAD), which is widely expressed within the CNS, catalyzing the conversion of the excitatory neurotransmitter l-glutamate to the inhibitory GABA.
CAR-T therapy such as KYV-101 may be an effective treatment for SPS, by targeting these autoreactive B cells. Using chimeric antigen receptor (CAR) T-cell technology, engineered T cells with receptors are designed to recognize and eliminate B cells, including those that produce GAD autoantibodies. This approach aims to intervene at the root of the autoimmune response, offering a precise and potentially transformative treatment for SPS. CAR-T cell therapy holds promise as a targeted and effective intervention, addressing the autoimmune component directly and potentially halting disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KYV-101 CAR-T cells with lymphodepletion conditioning | Experimental | Biological: Standard lymphodepletion regimenDosing with KYV-101 CAR T cells |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Subject must have been diagnosed SPS per the following criteria:
- Active symptoms with inadequate response to at least one immunomodulatory therapy.
- Stiffness index ≥2.
- At least 20 of the 25 enrolled subjects should be ambulatory.
Key exclusion criteria (4 listed)
- Bedridden subjects for more than 3 months.
- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis, non-SPS progressive neurologic condition or progressive multifocal leukoencephalopathy (PML).
- History of stroke, seizure, dementia, Parkinson's disease, cerebellar diseases, psychosis, aphasia, and any other neurologic disorder that is of a nature and severity that the investigator considers would increase the risk for the subject.
- Cardiac ejection fraction ≤ 40%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard lymphodepletion regimenAlso: Cyclophosphamide, FludarabineStandard lymphodepletion regimen | Biological | KYV-101 CAR-T cells with lymphodepletion conditioning |
Primary outcome
To evaluate efficacy of KYV-101
Time frame: Up to 12 months
Change in the Timed 25-Foot Walk (T25-FW) from baseline
To evaluate the safety of KYV-101
Time frame: Up to 12 months
Incidence of adverse events and laboratory abnormalities
4 secondary outcomes
To evaluate efficacy of KYV-101
Time frame: Up to 12 months
To evaluate efficacy of KYV-101
Time frame: Up to 12 months
To evaluate efficacy of KYV-101
Time frame: Up to 12 months
To evaluate efficacy of KYV-101
Time frame: Up to 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- BackgroundPiquet AL, et al. Miv-cel CD19 CAR T-cell therapy shows efficacy and safety in stiff person syndrome in a pivotal, multicenter, phase 2 study (KYSA-8). Presented at: American Academy of Neurology (AAN) Annual Meeting; April 18-21, 2026; Chicago, IL. Late Breaking Science Abstract 008.
- Background: PubMed 37059468Dalakas MC. Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology. Neurol Neuroimmunol Neuroinflamm. 2023 Apr 14;10(3):e200109. doi: 10.1212/NXI.0000000000200109. Print 2023 May.
- Background: PubMed 19349711Duddy ME, Baker MR. Stiff person syndrome. Front Neurol Neurosci. 2009;26:147-165. doi: 10.1159/000212375. Epub 2009 Apr 6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Kyverna Therapeutics
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Standard lymphodepletion regimen in people with Stiff-Person Syndrome and SPS, run by Kyverna Therapeutics at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate efficacy of KYV-101 (time frame: Up to 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06588491, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.