ANCA-IgG-positive ANCA Associated VasculitisPhase 1/2IDEALNCT06590545
Anti-CD 19 CAR-T Cell Therapy in Patients With ANCA Vasculitis
A Phase 1/2 study testing KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy in people with ANCA-IgG-positive ANCA Associated Vasculitis, run by David Simon.
Trial summary
The goal of this phase I/II clinical trial is to investigate anti-CD 19 chimeric antigen receptor T cell (CAR-T cell) therapy in patients with antineutrophil cytoplasmic antibodies (ANCA) immunoglobulin (IgG) positive ANCA associated vasculitis (AAV). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- ANCA-IgG-positive ANCA Associated Vasculitis
- What is being tested?
- KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- No sites listed yet
- Study dates
- Jan 2025to Jul 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Understand and voluntarily sign an informed consent form
- Male or female, age ≥ 18 and ≤ 75 years at ti me of consent
- Able to adhere to the study visits and protocol
- Fulfilment of
- EITHER both of the following
- 2022 ACR-EULAR classification criteria for granulomatosis with polyangiitis (GPA)
Show all 15Show fewer
- detectable anti-PR3 antibodies (≥ 20 AU/ml in CLIA) at screening
- OR both of the following
- 2022 ACR/EULAR classification criteria for microscopic polyangiitis (MPA)
- detectable anti-MPO antibodies (≥ 10 AU/ml in CLIA) at screening
- Active disease, defined as Clinical activity (BVAS ≥ 3) at screening
- Insufficient response or intolerance/contraindication to glucocorticoids and to at least one of the following treatments: rituximab, mycophenolate mofetil, azathioprine, methotrexate, cyclophosphamide, avacopan. Insufficient response is defined as having disease activity based on the definition explained in the previous bullet point
- Male subjects unless surgically sterile, must agree to use two acceptable methods for contraception (e.g. spermicide and condom) during the trial and refrain from fathering a child starting from the time of signing the Informed Consent Form (ICF) until 12 months after dosing of the IMP
- Females of childbearing potential (FCBP) must have a negative urine pregnancy test at screening and must agree to use a highly effective contraceptive method (Pearl index less than 1) starting from the time of signing the ICF and for 12 months after dosing of the IMP
- Updated vaccination record according to the STIKO recommendations for immuno-compromised patients
Who cannot join
- ANC less than 500/µl, ALC less than 100/µl or hemoglobin less than 8g/dl, absolute CD3+T cell count less than 100/µl at screening
- Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), or heart or pulmonary (NYHA IV, blood oxygenation less than 92%) function
- Clinically relevant rapidly progressive glomerulonephritis or pulmonary alveolar hemorrhage
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy)
- History of bone marrow/ hematopoietic stem cell or solid organ transplantation
Show all 17Show fewer
- Any concomitant severe active infection, e.g. HIV, hepatitis B or C, SARS-CoV-2 (COVID-19), or active tuberculosis as defined by a positive Quantiferon TB-test. If presence of latent tuberculosis is established then treatment according to local guide-lines must have been initiated prior to enrollment
- Pregnant or lactating females
- Females who are intending to conceive during the study
- Known hypersensitivity to any drug components
- Malignancy in the last 5 years before screening (except adequately treated basal or squamous cell skin cancer)
- Requirement for immunization with live vaccine during the study period or within 14 days preceding leukapheresis,
- Subjects who are younger than 18 years or are incapable to understand the aim, importance and consequences of the study and to give legal informed consent (accord-ing to § 40 Abs. 4 and § 41 Abs. 2 and Abs. 3 AMG),
- Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the Investigator, may increase the risks associated with study participa-tion or study agent administration, or may interfere with interpretation of results,
- Subjects who possibly are dependent on the Sponsor, the Principal Investigator or Investigator (e.g. family members).
- Subjects who are institutionalized by order of court or public authority,
- Subjects participating in another clinical trial with an investigational medicinal product or medical device (3 months before this trial).
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Anti-CD 19 CAR-T Cell Therapy in Patients With ANCA Vasculitis: a Two-stage Interventional, Prospective, Open-label, Phase I/II Trial in Patients With Active, Treatment Refractory, ANCA-IgG-positive Vasculitis
The goal of this phase I/II clinical trial is to investigate anti-CD 19 chimeric antigen receptor T cell (CAR-T cell) therapy in patients with antineutrophil cytoplasmic antibodies (ANCA) immunoglobulin (IgG) positive ANCA associated vasculitis (AAV).
The main questions it aims to answer are:
Read more
- To assess the safety of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory, ANCA-IgG-positive AAV
- To assess the clinical efficacy of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory ANCA-IgG-positive AAV
- To assess the ANCA seroconversion rate in subjects with active, treatment refractory ANCA-IgG-positive AAV
Participants will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR-T cell immunotherapy. Follow-up time is 52 weeks with regular visits at the site.
Read the detailed description
This study aims to investigate the use of KYV101 (a fully human anti-CD19 CAR T cell therapy) in ANCA-IgG-positive AAV patients who are refractory to previous treatments. This study is designed to determine (i) the safety of this B-cell targeted therapy, (ii) the clinical efficacy, (iii) the impact on the immunological status of the patient and in particular on ANCA positivity, and (iv) the ability to induce long-term (deep) clinical and molecular remission and drug-free survival.
The investigational product (IMP), KYV-101, is an autologous fully-human anti-CD19 CAR T-cell immunotherapy. Before IMP infusion, patients will receive a premedication of 4 mg Dimetindenmaleat iv or equivalent antihistamine and 1000 mg oral acetaminophene. Prophylactic doses of acyclovir of 400mg 2x daily as well as cotrimoxazole 960mg 3x weekly will be administered orally following CAR T cell infusion until week 24. Tocilizumab 8mg/kg will be administered intravenously when required for treatment of IMP-related cytokine release syndrome. Dexamethasone as needed will be administered intravenously when required for treatment of neurological adverse event (ICANS).
Follow-up time is 52 weeks with regular visits at the site.
- Being tested
- KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy
- Keywords
- ANCA, CAR-T-Cell, Vasculitis, Seroconversion, anti-CD19
- Medical subject headings
- Vasculitis, HIV Seropositivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapyDrug
A dosage of 1x10^8 KYV-101 CAR+ T cells will be administered intravenously as a single infusion.
| Study group | Role | What they receive |
|---|---|---|
| KYV-101, anti-CD19 CAR T-cell immunotherapy. | Experimental | A dosage of 1x10^8 KYV-101 CAR+ T cells will be administered intravenously as a single infusion. Receives: Drug: KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of subjects experiencing a cytokine release syndrome
The primary safety outcome in Phase I variable will be measured as the number of subjects experiencing a cytokine release syndrome (CRS) or an immune cell-associated neurotoxicity syndrome (ICANS) as well as adverse events (AE) and serious adverse events (SAE) due to investigational medical product (IMP) within the first 4 weeks.
Measured: Screening up to week 4
antineutrophil cytoplasmic antibodies (ANCA) seroconversion rate
The primary efficacy outcome variable of Phase II will be the antineutrophil cytoplasmic antibodies (ANCA) seroconversion rate in subjects with active, treatment refractory ANCA-IgG-positive AAV at week 24.
Measured: week 24
adverse events and serious adverse events due to investigational medical product
The primary safety outcome variable of Phase II will be measured as adverse events (AE) and serious adverse events (SAE) due to investigational medical product (IMP) throughout the whole study.
Measured: up to 52 weeks
Secondary outcomes (23)
immunoglobulin IgG
Change in total IgG immunoglobulins over time
Measured: up to week 52
immunoglobulin IgG subclasses
Change in total IgG subclasses mmunoglobulins over time
Measured: up to week 52
immunoglobulin IgA
Change in total IgA immunoglobulins over time
Measured: up to week 52
immunoglobulin IgM
Change in total IgM immunoglobulins over time
Measured: up to week 52
Change in PR3
Change in PR3 specific plasmablasts and B-cells
Measured: up to week 52
Change in MPO
Change in MPO specific plasmablasts and B-cells
Measured: up to week 52
number of plasmablasts
Change in the number of plasmablasts cell over time
Measured: up to week 52
number of B cells
Change in the number of pB cells numbers over time
Measured: up to week 52
number of T cells
Change in the number T cells numbers over time
Measured: up to week 52
relapse/flare
Time to relapse/flare
Measured: up to 52 weeks
time without immunosuppression
Survival time without immunosuppression
Measured: up to 52 weeks
Vasculitis Damage Index
Change of Vasculitis Damage Index (VDI) compared to baseline
Measured: up to 52 weeks
Flares
Number of flares
Measured: up to 52 weeks
Birmingham Vasculitis Activity Score
Change in Birmingham Vasculitis Activity Score (BVAS) compared to baseline
Measured: up to 52 weeks
B cell depletion
Duration of B cell depletion in the peripheral blood
Measured: up to 52 weeks
persistence of CAR T cells
Duration of persistence of CAR T cells in the peripheral blood
Measured: up to 52 weeks
Change in anti-PR3 antibodies
Change in anti-PR3 antibodies over time (GPA)
Measured: up to 52 weeks
anti-MPO antibodies
Change in anti-MPO antibodies over time
Measured: up to 52 weeks
anti-MPO antibodies
Percentage of subjects with normal anti-MPO antibodies (less than 10 AU/ml)
Measured: up to week 52
normal anti-PR3 antibodies
Percentage of subjects with normal anti-PR3 antibodies (less than 20 AU/ml in CLIA)
Measured: up to 52 weeks
EULAR sustained remission criteria
Percentage of patients who reach European Alliance of Associations for Rheumatology (EULAR) sustained remission criteria (absence of typical signs, symptoms, or other features of active ANCA associated vasculitis)
Measured: up to week 52
reach EULAR response criteria
Percentage of patients who reach European Alliance of Associations for Rheumatology (EULAR) response criteria (≥ 50% reduction of Birmingham Vasculitis Activity Score (BVAS) compared to baseline
Measured: up to 52 weeks
number of CAR-T cells
number of CAR-T cells in the patient over time
Measured: up to 52 weeks
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 startJan 2025 (estimated)
- Primary completionJan 2027 (estimated)
- Study completionJul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for ANCA-IgG-positive ANCA Associated VasculitisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- this is a two-stage interventional, prospective, open-label study. This study has one treatment arm (open-label KYV101), but sequential treatment (two groups). Second group of participants are assigned to receive interventions based on the achievement of the previous milestone (28 days after treatment of the third patient of group 1). A data safety monitoring board (DSMB) will decide whether to proceed to phase II ≥ 28 days after treatment of the third subject.
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Simon
- Sponsor type
- University, hospital or other
- Collaborators
- Kyverna Therapeutics
- Responsible party
- Sponsor-investigator, David Simon, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06590545
- Sponsor's protocol ID
- CCM-RNT-202402
- Other IDs
- 2024-517303-36-00
- Acronym
- IDEAL
- Status last verified
- Aug 2024
- First submitted
- 4 Sep 2024
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: results will be published anonymized and summarized
Publications
Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764.
PubMed 36927642Han WK, Choi HK, Roth RM, McCluskey RT, Niles JL. Serial ANCA titers: useful tool for prevention of relapses in ANCA-associated vasculitis. Kidney Int. 2003 Mar;63(3):1079-85. doi: 10.1046/j.1523-1755.2003.00821.x.
PubMed 12631091Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
PubMed 38381673Schett G, Mackensen A, Mougiakakos D. CAR T-cell therapy in autoimmune diseases. Lancet. 2023 Nov 25;402(10416):2034-2044. doi: 10.1016/S0140-6736(23)01126-1. Epub 2023 Sep 22.
PubMed 37748491Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
PubMed 36109639Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
PubMed 34347960Lodka D, Zschummel M, Bunse M, Rousselle A, Sonnemann J, Kettritz R, Hopken UE, Schreiber A. CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury. Ann Rheum Dis. 2024 Mar 12;83(4):499-507. doi: 10.1136/ard-2023-224875.
PubMed 38182404Treppo E, Binutti M, Agarinis R, De Vita S, Quartuccio L. Rituximab Induction and Maintenance in ANCA-Associated Vasculitis: State of the Art and Future Perspectives. J Clin Med. 2021 Aug 24;10(17):3773. doi: 10.3390/jcm10173773.
PubMed 34501224Steinmetz OM, Velden J, Kneissler U, Marx M, Klein A, Helmchen U, Stahl RA, Panzer U. Analysis and classification of B-cell infiltrates in lupus and ANCA-associated nephritis. Kidney Int. 2008 Aug;74(4):448-57. doi: 10.1038/ki.2008.191. Epub 2008 Jun 4.
PubMed 18528326Holden NJ, Williams JM, Morgan MD, Challa A, Gordon J, Pepper RJ, Salama AD, Harper L, Savage CO. ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process. Ann Rheum Dis. 2011 Dec;70(12):2229-33. doi: 10.1136/ard.2011.153890. Epub 2011 Aug 21.
PubMed 21859691Falk RJ, Terrell RS, Charles LA, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115-9. doi: 10.1073/pnas.87.11.4115.
PubMed 2161532Kitching AR, Anders HJ, Basu N, Brouwer E, Gordon J, Jayne DR, Kullman J, Lyons PA, Merkel PA, Savage COS, Specks U, Kain R. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug 27;6(1):71. doi: 10.1038/s41572-020-0204-y.
PubMed 32855422Brudno JN, Lam N, Vanasse D, Shen YW, Rose JJ, Rossi J, Xue A, Bot A, Scholler N, Mikkilineni L, Roschewski M, Dean R, Cachau R, Youkharibache P, Patel R, Hansen B, Stroncek DF, Rosenberg SA, Gress RE, Kochenderfer JN. Author Correction: Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Nat Med. 2020 May;26(5):803. doi: 10.1038/s41591-020-0864-x.
PubMed 32291416
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anti-CD 19 CAR-T Cell Therapy in Patients With ANCA Vasculitis: a Two-stage Interventional, Prospective, Open-label, Phase I/II Trial in Patients With Active, Treatment Refractory, ANCA-IgG-positive Vasculitis
- ClinicalTrials.gov ID
- NCT06590545
- Acronym / sponsor ID
- IDEAL / CCM-RNT-202402
- Keywords
- ANCA, CAR-T-Cell, Vasculitis, Seroconversion, anti-CD19
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- David SimonUniversity, hospital or other
- Collaborators
- Kyverna Therapeutics
- Study start
- Jan 2025 (estimated)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jul 2027 (estimated)
- 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.
The goal of this phase I/II clinical trial is to investigate anti-CD 19 chimeric antigen receptor T cell (CAR-T cell) therapy in patients with antineutrophil cytoplasmic antibodies (ANCA) immunoglobulin (IgG) positive ANCA associated vasculitis (AAV).
The main questions it aims to answer are:
- To assess the safety of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory, ANCA-IgG-positive AAV
- To assess the clinical efficacy of anti-CD19 CAR-T cell therapy in subjects with active, treatment refractory ANCA-IgG-positive AAV
- To assess the ANCA seroconversion rate in subjects with active, treatment refractory ANCA-IgG-positive AAV
Participants will receive a single dose of KYV-101 i.v., an autologous fully-human anti-CD19 CAR-T cell immunotherapy. Follow-up time is 52 weeks with regular visits at the site.
Detailed description
This study aims to investigate the use of KYV101 (a fully human anti-CD19 CAR T cell therapy) in ANCA-IgG-positive AAV patients who are refractory to previous treatments. This study is designed to determine (i) the safety of this B-cell targeted therapy, (ii) the clinical efficacy, (iii) the impact on the immunological status of the patient and in particular on ANCA positivity, and (iv) the ability to induce long-term (deep) clinical and molecular remission and drug-free survival.
The investigational product (IMP), KYV-101, is an autologous fully-human anti-CD19 CAR T-cell immunotherapy. Before IMP infusion, patients will receive a premedication of 4 mg Dimetindenmaleat iv or equivalent antihistamine and 1000 mg oral acetaminophene. Prophylactic doses of acyclovir of 400mg 2x daily as well as cotrimoxazole 960mg 3x weekly will be administered orally following CAR T cell infusion until week 24. Tocilizumab 8mg/kg will be administered intravenously when required for treatment of IMP-related cytokine release syndrome. Dexamethasone as needed will be administered intravenously when required for treatment of neurological adverse event (ICANS).
Follow-up time is 52 weeks with regular visits at the site.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- this is a two-stage interventional, prospective, open-label study. This study has one treatment arm (open-label KYV101), but sequential treatment (two groups). Second group of participants are assigned to receive interventions based on the achievement of the previous milestone (28 days after treatment of the third patient of group 1). A data safety monitoring board (DSMB) will decide whether to proceed to phase II ≥ 28 days after treatment of the third subject.
| Arm | Type | Receives |
|---|---|---|
| KYV-101, anti-CD19 CAR T-cell immunotherapy. | Experimental | Drug: KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapyA dosage of 1x10^8 KYV-101 CAR+ T cells will be administered intravenously as a single infusion. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Understand and voluntarily sign an informed consent form
- Male or female, age ≥ 18 and ≤ 75 years at ti me of consent
- Able to adhere to the study visits and protocol
- Fulfilment of
- EITHER both of the following
Key exclusion criteria (17 listed)
- ANC less than 500/µl, ALC less than 100/µl or hemoglobin less than 8g/dl, absolute CD3+T cell count less than 100/µl at screening
- Severely impaired renal (eGFR ≤ 30 ml/min/m2), liver (Child Pugh C), or heart or pulmonary (NYHA IV, blood oxygenation less than 92%) function
- Clinically relevant rapidly progressive glomerulonephritis or pulmonary alveolar hemorrhage
- Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
- Prior treatment with anti-CD19 antibody therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR T cell therapy)
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 |
|---|---|---|
| KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapyA dosage of 1x10^8 KYV-101 CAR+ T cells will be administered intravenously as a single infusion. | Drug | KYV-101, anti-CD19 CAR T-cell immunotherapy. |
Primary outcome
number of subjects experiencing a cytokine release syndrome
Time frame: Screening up to week 4
The primary safety outcome in Phase I variable will be measured as the number of subjects experiencing a cytokine release syndrome (CRS) or an immune cell-associated neurotoxicity syndrome (ICANS) as well as adverse events (AE) and serious adverse events (SAE) due to investigational medical product (IMP) within the first 4 weeks.
antineutrophil cytoplasmic antibodies (ANCA) seroconversion rate
Time frame: week 24
The primary efficacy outcome variable of Phase II will be the antineutrophil cytoplasmic antibodies (ANCA) seroconversion rate in subjects with active, treatment refractory ANCA-IgG-positive AAV at week 24.
adverse events and serious adverse events due to investigational medical product
Time frame: up to 52 weeks
The primary safety outcome variable of Phase II will be measured as adverse events (AE) and serious adverse events (SAE) due to investigational medical product (IMP) throughout the whole study.
23 secondary outcomes
immunoglobulin IgG
Time frame: up to week 52
immunoglobulin IgG subclasses
Time frame: up to week 52
immunoglobulin IgA
Time frame: up to week 52
immunoglobulin IgM
Time frame: up to week 52
Change in PR3
Time frame: up to week 52
Change in MPO
Time frame: up to week 52
number of plasmablasts
Time frame: up to week 52
number of B cells
Time frame: up to week 52
number of T cells
Time frame: up to week 52
relapse/flare
Time frame: up to 52 weeks
time without immunosuppression
Time frame: up to 52 weeks
Vasculitis Damage Index
Time frame: up to 52 weeks
Flares
Time frame: up to 52 weeks
Birmingham Vasculitis Activity Score
Time frame: up to 52 weeks
B cell depletion
Time frame: up to 52 weeks
persistence of CAR T cells
Time frame: up to 52 weeks
Change in anti-PR3 antibodies
Time frame: up to 52 weeks
anti-MPO antibodies
Time frame: up to 52 weeks
anti-MPO antibodies
Time frame: up to week 52
normal anti-PR3 antibodies
Time frame: up to 52 weeks
EULAR sustained remission criteria
Time frame: up to week 52
reach EULAR response criteria
Time frame: up to 52 weeks
number of CAR-T cells
Time frame: up to 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Results publication: PubMed 36927642Hellmich B, Sanchez-Alamo B, Schirmer JH, Berti A, Blockmans D, Cid MC, Holle JU, Hollinger N, Karadag O, Kronbichler A, Little MA, Luqmani RA, Mahr A, Merkel PA, Mohammad AJ, Monti S, Mukhtyar CB, Musial J, Price-Kuehne F, Segelmark M, Teng YKO, Terrier B, Tomasson G, Vaglio A, Vassilopoulos D, Verhoeven P, Jayne D. EULAR recommendations for the management of ANCA-associated vasculitis: 2022 update. Ann Rheum Dis. 2024 Jan 2;83(1):30-47. doi: 10.1136/ard-2022-223764.
- Results publication: PubMed 12631091Han WK, Choi HK, Roth RM, McCluskey RT, Niles JL. Serial ANCA titers: useful tool for prevention of relapses in ANCA-associated vasculitis. Kidney Int. 2003 Mar;63(3):1079-85. doi: 10.1046/j.1523-1755.2003.00821.x.
- Results publication: PubMed 38381673Muller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Volkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schafer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Kronke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917.
- Results publication: PubMed 37748491Schett G, Mackensen A, Mougiakakos D. CAR T-cell therapy in autoimmune diseases. Lancet. 2023 Nov 25;402(10416):2034-2044. doi: 10.1016/S0140-6736(23)01126-1. Epub 2023 Sep 22.
- Results publication: PubMed 36109639Mackensen A, Muller F, Mougiakakos D, Boltz S, Wilhelm A, Aigner M, Volkl S, Simon D, Kleyer A, Munoz L, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rosler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Buettner C, Habenicht KM, Winkler TH, Kronke G, Schett G. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med. 2022 Oct;28(10):2124-2132. doi: 10.1038/s41591-022-02017-5. Epub 2022 Sep 15.
- Results publication: PubMed 34347960Mougiakakos D, Kronke G, Volkl S, Kretschmann S, Aigner M, Kharboutli S, Boltz S, Manger B, Mackensen A, Schett G. CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2021 Aug 5;385(6):567-569. doi: 10.1056/NEJMc2107725. No abstract available.
- Results publication: PubMed 38182404Lodka D, Zschummel M, Bunse M, Rousselle A, Sonnemann J, Kettritz R, Hopken UE, Schreiber A. CD19-targeting CAR T cells protect from ANCA-induced acute kidney injury. Ann Rheum Dis. 2024 Mar 12;83(4):499-507. doi: 10.1136/ard-2023-224875.
- Results publication: PubMed 34501224Treppo E, Binutti M, Agarinis R, De Vita S, Quartuccio L. Rituximab Induction and Maintenance in ANCA-Associated Vasculitis: State of the Art and Future Perspectives. J Clin Med. 2021 Aug 24;10(17):3773. doi: 10.3390/jcm10173773.
- Results publication: PubMed 18528326Steinmetz OM, Velden J, Kneissler U, Marx M, Klein A, Helmchen U, Stahl RA, Panzer U. Analysis and classification of B-cell infiltrates in lupus and ANCA-associated nephritis. Kidney Int. 2008 Aug;74(4):448-57. doi: 10.1038/ki.2008.191. Epub 2008 Jun 4.
- Results publication: PubMed 21859691Holden NJ, Williams JM, Morgan MD, Challa A, Gordon J, Pepper RJ, Salama AD, Harper L, Savage CO. ANCA-stimulated neutrophils release BLyS and promote B cell survival: a clinically relevant cellular process. Ann Rheum Dis. 2011 Dec;70(12):2229-33. doi: 10.1136/ard.2011.153890. Epub 2011 Aug 21.
- Results publication: PubMed 2161532Falk RJ, Terrell RS, Charles LA, Jennette JC. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115-9. doi: 10.1073/pnas.87.11.4115.
- Results publication: PubMed 32855422Kitching AR, Anders HJ, Basu N, Brouwer E, Gordon J, Jayne DR, Kullman J, Lyons PA, Merkel PA, Savage COS, Specks U, Kain R. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug 27;6(1):71. doi: 10.1038/s41572-020-0204-y.
- Individual participant dataSharing planned: No. results will be published anonymized and summarized
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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy in people with ANCA-IgG-positive ANCA Associated Vasculitis, run by David Simon.
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 15 inclusion and 17 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: opening soon, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Nils Simon, Dr. med. habil. (+4930450513017, david.simon@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of subjects experiencing a cytokine release syndrome (time frame: Screening up to week 4). The study lists 3 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 NCT06590545, which also lists 13 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 19 Sep 2024.