NCT06152172

Brief Summary

The purpose of this study is to assess the safety, tolerability, and clinical activity of KYV 101 (a fully-human anti-CD19 CAR T-cell therapy) in adult subjects with B cell-driven autoimmune diseases. The trial anticipates enrolling participants to reach a maximum of 24 participants who will receive 1 dose of KYV-101 and will be followed for 2 years.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
9mo left

Started Aug 2024

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress70%
Aug 2024Feb 2027

First Submitted

Initial submission to the registry

November 21, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

November 30, 2023

Completed
8 months until next milestone

Study Start

First participant enrolled

August 5, 2024

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2027

Last Updated

February 18, 2026

Status Verified

February 1, 2026

Enrollment Period

2.5 years

First QC Date

November 21, 2023

Last Update Submit

February 16, 2026

Conditions

Idiopathic Inflammatory MyopathiesDiffuse Cutaneous Systemic SclerosisSLE NephritisANCA Associated Vasculitis

Outcome Measures

Primary Outcomes (16)

  • Incidence and severity of AEs in IIM.

    Incidence and severity of AEs in Idiopathic inflammatory myopathies

    3 months after CAR infusion.

  • Incidence and severity of AEs in IIM.

    Incidence and severity of AEs in Idiopathic inflammatory myopathies.

    6 months after CAR infusion.

  • Incidence and severity of AEs in IIM.

    Incidence and severity of AEs in Idiopathic inflammatory myopathies.

    12 months after CAR infusion.

  • Incidence and severity of AEs in IIM.

    Incidence and severity of AEs in Idiopathic inflammatory myopathies.

    24 months after CAR infusion.

  • Incidence and severity of AEs in DCSS

    Incidence and severity of AEs in diffuse cutaneous systemic sclerosis

    3 months after CAR infusion.

  • Incidence and severity of AEs in DCSS

    Incidence and severity of AEs in diffuse cutaneous systemic sclerosis

    6 months after CAR infusion.

  • Incidence and severity of AEs in DCSS

    Incidence and severity of AEs in diffuse cutaneous systemic sclerosis

    12 months after CAR infusion.

  • Incidence and severity of AEs in DCSS

    Incidence and severity of AEs in diffuse cutaneous systemic sclerosis

    24 months after CAR infusion.

  • Incidence and severity of AEs in SLE Nephritis

    Incidence and severity of AEs in systemic lupus erythematosus nephritis.

    3 months after CAR infusion.

  • Incidence and severity of AEs in SLE Nephritis

    Incidence and severity of AEs in systemic lupus erythematosus nephritis.

    6 months after CAR infusion.

  • Incidence and severity of AEs in SLE Nephritis

    Incidence and severity of AEs in systemic lupus erythematosus nephritis.

    12 months after CAR infusion.

  • Incidence and severity of AEs in SLE Nephritis

    Incidence and severity of AEs in systemic lupus erythematosus nephritis.

    24 months after CAR infusion.

  • Incidence and severity of AEs in AAV

    Incidence and severity of AEs in ANCA-Associated vasculitis

    3 months after CAR infusion.

  • Incidence and severity of AEs in AAV

    Incidence and severity of AEs in ANCA-Associated vasculitis

    6 months after CAR infusion.

  • Incidence and severity of AEs in AAV

    Incidence and severity of AEs in ANCA-Associated vasculitis

    12 months after CAR infusion.

  • Incidence and severity of AEs in AAV

    Incidence and severity of AEs in ANCA-Associated vasculitis

    24 months after CAR infusion.

Study Arms (4)

IIM

EXPERIMENTAL

Participants with idiopathic inflammatory myopathy will receive will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Drug: KYV-101Drug: CyclophosphamideDrug: Fludarabine

DCSS

EXPERIMENTAL

Participants with diffuse cutaneous systemic sclerosis will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Drug: KYV-101Drug: CyclophosphamideDrug: Fludarabine

SLE

EXPERIMENTAL

Participants with SLE-related nephritis will receive will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Drug: KYV-101Drug: CyclophosphamideDrug: Fludarabine

AAV

EXPERIMENTAL

Participants with ANCA-associated vasculitis will receive will receive lymphodepleting chemotherapy of cyclophosphamide and fludarabine prior to administration of KYV-101.

Drug: KYV-101Drug: CyclophosphamideDrug: Fludarabine

Interventions

KYV-101DRUG

The KYV-101 will be administered IV as a single infusion dosed at 1×108 CAR+ T cells.

AAVDCSSIIMSLE
CyclophosphamideDRUG

Lymphodepleting chemotherapy of cyclophosphamide (CYC) 300 mg/m2

AAVDCSSIIMSLE
FludarabineDRUG

Lymphodepleting chemotherapy of Fludarabine (FLU) 30 mg/m2 intravenously (IV)

AAVDCSSIIMSLE

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Idiopathic inflammatory myopathy (including dermatomyositis, antisynthetase syndrome, immune mediated necrotizing myopathy, and polymyositis):
  • Diagnosis of probable or definite (\>55%) idiopathic inflammatory myopathy, including dermatomyositis, anti-synthetase myopathy, immune-mediated necrotizing myopathy (including anti-HMGCoR-myopathy, anti-SRP myopathy), polymyositis, according to the 2017 ACR/EULAR Classification Criteria for idiopathic inflammatory myopathies (Lundberg, Tjarnlund et al. 2017).
  • Disease severity and minimal core set measure criteria: MMT-8 score \<136/150, with at least 2 other abnormal core set measures (CSMs) from the following:
  • Patient global VAS≥3 on a 1-10 scale (Appendix 3).
  • Physician's global VAS ≥3 on a 1-10 scale (Appendix 4).
  • Global extramuscular activity score ≥2 cm (Appendix 5).
  • Elevation of at least one of the muscle enzymes (CK, AST, ALT, aldolase, LDH) \>1.5 times upper limit of normal (Appendix 6).
  • HAQ-DI ≥0.25 (Appendix 7).
  • Active disease as per one of the following:
  • Creatine kinase ≥4×ULN.
  • Active rashes of dermatomyositis such that CDASI-activity ≥6 (Appendix 8).
  • Evidence on MRI of active myositis within last 6 months.
  • Evidence on EMG of active myositis within last 6 months.
  • Muscle biopsy evidence of active myositis within last 6 months
  • Positive, at screening or by documented medical history, for one myositis-specific per pre specified list (Table 3), except for patients with DM who need not have a positive test for a myositis-specific antibody.
  • +77 more criteria

You may not qualify if:

  • Idiopathic inflammatory myopathy:
  • a. Evidence of any of the following:
  • Severe muscle damage as per one of the following criteria:
  • Myositis Global Damage Index (MDI) ≥5.
  • Severe proximal muscle atrophy of upper or lower extremity on MRI.
  • Severe proximal muscle atrophy of upper or lower extremity on clinical examination.
  • Wheelchair-bound at home.
  • MMT-8 of ≤80.
  • MDA5-positive rapidly progressing disease (subjects with stable ILD not requiring supplemental oxygen are eligible).
  • Patients with ILD requiring O2 therapy and/or FVC ≤45% of predicted.
  • Generalized, severe musculoskeletal or neuro-muscular conditions other than IIM that prevent a sufficient assessment of the patient by the physician.
  • Diffuse cutaneous systemic sclerosis:
  • b. Subject with any of the following:
  • Patients with ILD with any of the following
  • Requiring O2 therapy and/or FVC ≤45% of predicted or DLCO ≤40% of predicted at screening
  • +43 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital of the Universithy of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

MyositisScleroderma, DiffuseLupus NephritisAnti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis

Interventions

Cyclophosphamidefludarabine

Condition Hierarchy (Ancestors)

Muscular DiseasesMusculoskeletal DiseasesNeuromuscular DiseasesNervous System DiseasesScleroderma, SystemicConnective Tissue DiseasesSkin and Connective Tissue DiseasesSkin DiseasesGlomerulonephritisNephritisKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesLupus Erythematosus, SystemicAutoimmune DiseasesImmune System DiseasesSystemic VasculitisVasculitisVascular DiseasesCardiovascular DiseasesSkin Diseases, Vascular

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants will be enrolled based on their disease.
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Director, Cell Therapy and Transplant, University of Pennsylvania

Study Record Dates

First Submitted

November 21, 2023

First Posted

November 30, 2023

Study Start

August 5, 2024

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2027

Last Updated

February 18, 2026

Record last verified: 2026-02

Locations

US(1)