A Phase 1, Open-Label, Single Center Study of KYV-101, an Autologous Fully-Human Anti-CD19 Chimeric Antigen Receptor T-Cell (CD19 CAR T) Therapy in Subjects With Non-relapsing and Progressive Forms of Multiple Sclerosis
A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis
• Patient is ≥ 18 years old, and ≤65 years of age, at time of screening visit.
• Diagnosis of MS according to the 2017 McDonald Criteria.
• Progressive MS by 2014 Lublin MS phenotypic criteria.
• Presence of varicella-zoster virus (VZV) antibodies, or completion of at least one dose of the varicella zoster glycoprotein E (gE) Shingrix vaccine at least four weeks prior to treatment.
• Presence of anti EBV antibodies.
• Organ and Marrow Function
‣ Absolute neutrophil count (ANC) ≥ 2000/uL.
⁃ Platelet count ≥ 150,000/uL.
⁃ Absolute lymphocyte count ≥ 1000/uL.
⁃ Serum immunoglobulin G (IgG) ≥ 500mg/dL.
⁃ Hemoglobin ≥ 9 g/dL.
⁃ Adequate renal, hepatic, pulmonary and cardiac function defined as:
• Creatinine ≤ 2mg/dL or creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min.
∙ Serum alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).
∙ Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome
∙ Cardiac ejection fraction ≥ 40%, no evidence of physiologically significant pericardial effusion as determined by an ECHO, and no clinically significant ECG findings.
∙ Baseline oxygen saturation \> 94% on room air.
• Testing for
‣ Hepatitis B core antibody (HBc Ab)
⁃ Hepatitis C antibody (HCV Ab)
⁃ Hepatitis B surface antigen (Hep B surf. AG)
⁃ HIV 1\&2 Ab
⁃ Syphilis Screen
⁃ Human T-cell lymphotropic virus (HTLV) Ab I \& II
⁃ Nucleic acid test multiplex (NAT MPX) for HIV, HCV, HBV
⁃ Herpes Simplex Virus 1 \& 2 IgG panel
⁃ Varicella-Zoster (VZ) IgG
⁃ Cytomegalovirus (CMV) Total Ab
• Must be seronegative for HIV-1 RNA polymerase chain reaction (PCR); HIV 1 and HIV 2 Ab (antibody); HTLV-1 and HTLV-2 Ab; PCR+ or negative surface antigen for hepatitis B; negative for the Treponema pallidum antibody Syphilis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 40 days of apheresis procedures.
• Females of childbearing potential have a negative serum or urine pregnancy test because of the potentially dangerous/unknown effects on the fetus. Females who have undergone hysterectomy or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
• Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice highly effective birth control from the time of enrollment on this study and for the entire study period which is 12 months after receiving the CAR T cell infusion.
⁃ Ability to understand and the willingness to sign a written informed consent document. Patients must have signed informed consent to participate in the trial.
⁃ Adequate vital sign criterion with acceptable numerical ranges of:
∙ Systolic Blood Pressure (mmHg) ≥ 100 and ≤ 150
‣ Diastolic Blood pressure (mmHg) ≥ 60 and ≤ 90
‣ To ensure subject safety and stability, any subject who is noted to have a BP \> 150/90 mm Hg should be stable on anti-hypertensive medications with repeated BP ≤150/90 for at least one month prior to enrollment in the study
‣ Heart Rate ≥ 60 and ≤ 100 bpm
‣ Oral Temperature ≤ 37.7 C/afebrile
‣ Respiratory rate ≥ 12 and ≤ 20bpm