ClinicalTrials.gg
Sign In
Not yet recruitingNCT06590545IDEALUpdated Sep 19, 2024

Anti-CD 19 CAR-T Cell Therapy in Patients With ANCA Vasculitis

A Phase 1/2 interventional study of KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy in ANCA-IgG-positive ANCA Associated Vasculitis, sponsored by David Simon. Not yet recruiting. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-09-19.

Sponsored by David Simon · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
8
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study 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).

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.

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.

02

Conditions studied

  • ANCA-IgG-positive ANCA Associated Vasculitis

Keywords

  • ANCA
  • CAR-T-Cell
  • Vasculitis
  • Seroconversion
  • anti-CD19
03

In context

Vasculitis

231 studies on the registry are indexed under Vasculitis; 69 are open to participants now.

This study's planned enrollment of 8 is below the median of 48 across 120 interventional studies indexed under Vasculitis.

Browse Vasculitis studies →

Lead sponsor

This is the only study on the registry with David Simon as lead sponsor.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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)
    • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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).
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
8 participants (estimated)

Study arms

  • Experimental
    KYV-101, anti-CD19 CAR T-cell immunotherapy.

    A dosage of 1x10\^8 KYV-101 CAR+ T cells will be administered intravenously as a single infusion.

    Drug: KYV-101, an autologous fully-human anti-CD19 CAR T-cell immunotherapy

Interventions

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Screening up to week 4

  2. 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.

    Time frame: week 24

  3. 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.

    Time frame: up to 52 weeks

Secondary outcomes

  1. immunoglobulin IgG

    Change in total IgG immunoglobulins over time

    Time frame: up to week 52

  2. immunoglobulin IgG subclasses

    Change in total IgG subclasses mmunoglobulins over time

    Time frame: up to week 52

  3. immunoglobulin IgA

    Change in total IgA immunoglobulins over time

    Time frame: up to week 52

  4. immunoglobulin IgM

    Change in total IgM immunoglobulins over time

    Time frame: up to week 52

  5. Change in PR3

    Change in PR3 specific plasmablasts and B-cells

    Time frame: up to week 52

  6. Change in MPO

    Change in MPO specific plasmablasts and B-cells

    Time frame: up to week 52

  7. number of plasmablasts

    Change in the number of plasmablasts cell over time

    Time frame: up to week 52

  8. number of B cells

    Change in the number of pB cells numbers over time

    Time frame: up to week 52

  9. number of T cells

    Change in the number T cells numbers over time

    Time frame: up to week 52

  10. relapse/flare

    Time to relapse/flare

    Time frame: up to 52 weeks

  11. time without immunosuppression

    Survival time without immunosuppression

    Time frame: up to 52 weeks

  12. Vasculitis Damage Index

    Change of Vasculitis Damage Index (VDI) compared to baseline

    Time frame: up to 52 weeks

  13. Flares

    Number of flares

    Time frame: up to 52 weeks

  14. Birmingham Vasculitis Activity Score

    Change in Birmingham Vasculitis Activity Score (BVAS) compared to baseline

    Time frame: up to 52 weeks

  15. B cell depletion

    Duration of B cell depletion in the peripheral blood

    Time frame: up to 52 weeks

  16. persistence of CAR T cells

    Duration of persistence of CAR T cells in the peripheral blood

    Time frame: up to 52 weeks

  17. Change in anti-PR3 antibodies

    Change in anti-PR3 antibodies over time (GPA)

    Time frame: up to 52 weeks

  18. anti-MPO antibodies

    Change in anti-MPO antibodies over time

    Time frame: up to 52 weeks

  19. anti-MPO antibodies

    Percentage of subjects with normal anti-MPO antibodies (less than 10 AU/ml)

    Time frame: up to week 52

  20. normal anti-PR3 antibodies

    Percentage of subjects with normal anti-PR3 antibodies (less than 20 AU/ml in CLIA)

    Time frame: up to 52 weeks

  21. 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)

    Time frame: up to week 52

  22. 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

    Time frame: up to 52 weeks

  23. number of CAR-T cells

    number of CAR-T cells in the patient over time

    Time frame: up to 52 weeks

07

Study locations

No study locations are listed for this record.

08

References and documents

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 36927642 ↗
  • Han 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 12631091 ↗
  • Muller 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 38381673 ↗
  • Schett 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 37748491 ↗
  • Mackensen 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 36109639 ↗
  • Mougiakakos 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 34347960 ↗
  • Lodka 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 38182404 ↗
  • Treppo 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 34501224 ↗
  • Steinmetz 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 18528326 ↗
  • Holden 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 21859691 ↗
  • Falk 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 2161532 ↗
  • Kitching 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 32855422 ↗
  • Brudno 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 ↗

Individual participant data

Plan to share: No — results will be published anonymized and summarized

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Start is estimated for Jan 2025; primary completion for Jan 2027, 24 months later.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 4, 2024
First posted
Sep 19, 2024
StartEst.
Jan 2025
Primary completionEst.
Jan 2027
CompletionEst.
Jul 2027
Last update
Sep 19, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 19, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06590545
Lead sponsor
David Simon
Collaborators
Kyverna Therapeutics
Responsible party
David Simon (Principal Investigator, Head of the Clinical Trial Unit, Charite University, Berlin, Germany) — Sponsor-investigator
First posted
Sep 19, 2024
Start date
Jan 2025 (estimated)
Primary completion
Jan 2027 (estimated)
Completion
Jul 2027 (estimated)
Last update
Sep 19, 2024

Study contacts

David Nils Simon, Dr. med. habil.
Contact
david.simon@charite.de
+4930450513017
Jan Zernicke, Dr. rer. medic.
Contact
jan.zernicke@charite.de
+4930450513227

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Mivocabtagene autoleucel

Other studies in this condition

Vasculitis →

Start the discussion