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New treatment option for Multiple Sclerosis
Official title A Study of Anti-CD19 Chimeric Antigen Receptor T-Cell ( CAR-T) Therapy in Subjects With Non-relapsing and Progressive Forms of Multiple Sclerosis
ClinicalTrials.gov ID: NCT06138132
What this study is testing
What is KYV-101 anti-CD19 CAR-T cell therapy?
KYV-101 anti-CD19 CAR-T cell therapy is an investigational medicine, being studied as a potential treatment for multiple sclerosis.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- A Study of Anti-CD19 Chimeric Antigen Receptor T Cell Therapy in Subjects with Non-relapsing and Progressive Forms of Multiple Sclerosis
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 to 65
You may be able to join if
- 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...
- Presence of anti EBV antibodies.
You likely can't join if
- History of neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody associated disease (MOGAD).
- Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or...
- Initiation of any DMT between the completion of apheresis and start of lymphodepletion (LD) chemotherapy. The use of methylprednisolone for bridging...
- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis or...
- History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
- History of sickle cell anemia or other hemoglobinopathy.
See the full eligibility criteria
Who can join
- 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 people 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...
- 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...
- Contraception: people 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...
- 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...
- Heart Rate ≥ 60 and ≤ 100 bpm
- Oral Temperature ≤ 37.7 C/afebrile
- Respiratory rate ≥ 12 and ≤ 20bpm
What rules you out
- History of neuromyelitis optica spectrum disorder (NMOSD) or MOG antibody associated disease (MOGAD).
- Prior treatment with any investigational agent within 3 months, or 5 half-lives, whichever is longer. Agents authorized by the FDA for prevention or treatment of severe acute respiratory syndrome coronavirus 2...
- Initiation of any DMT between the completion of apheresis and start of lymphodepletion (LD) chemotherapy. The use of methylprednisolone for bridging therapy between apheresis and start of LD chemotherapy will be allowed.
- History of CNS or spinal cord tumor, metabolic or infectious cause of myelopathy, genetically inherited progressive CNS disorder, sarcoidosis or non-MS progressive neurologic condition affecting ability to perform study...
- History of cytopenia consistent with the diagnosis of myelodysplastic syndrome (MDS).
- History of sickle cell anemia or other hemoglobinopathy.
- Coagulation abnormalities defined by: international normalized ratio (INR) \> 1.5, prothrombin time (PT) \> 14 seconds, partial thromboplastin time (PTT) \> 45 seconds to the exclusion criteria. Patients with positive...
- Presence of fungal, bacterial, viral, or other infection that is not controlled and/ or requiring hospitalization or treatment with IV antimicrobials within 4 weeks of screening. Simple urinary tract infection (UTI) and...
- Psychiatric disorder(s) or psychosocial circumstance(s) which in the opinion of the Stanford Transplant team caring for this potential patient would place the patient at an unacceptable risk.
- Presence or history of liver cirrhosis.
- History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
- Active infection with HIV, hepatitis B (HBsAg positive) or hepatitis C virus (anti-HCV positive) as the immunosuppression contained in this study may pose unacceptable risk. A prior history of hepatitis B or hepatitis C...
- Central nervous system (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease unrelated to MS that in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease (uncontrolled congestive heart failure) within 4 months of enrollment. people with...
- people receiving anticoagulation therapy or people with concomitant use of antiplatelet agents.
- History of Crohn's, rheumatoid arthritis, systemic lupus that required continued systemic immunosuppression/systemic disease modifying agents within the 2 years prior to trial enrollment.
- A primary immune deficiency disease
- In the investigator's judgment, the subject is unlikely to complete protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study. This includes contraindications or life-threatening allergies, hypersensitivity, or intolerance to KYV-101 or its...
- Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or how well it works of study treatment.
- Prior treatment with total lymphoid irradiation or mitoxantrone exceeding 36 mg/m2 cumulative dose
- Prior treatment with autologous hematopoietic stem cell transplantation, or prior history of cellular immunotherapy (eg. CAR T) or gene therapy directed at any target.
- Prior treatment with anti-CD20+ monoclonal antibody therapy within 9 months of trial initiation. A 30-day washout will be required for prior treatment with glatiramer acetate, interferon-beta, and fumarates. A 60-day...
- Prior history of solid organ transplantation
- Impaired cardiac function or clinically significant cardiac disease including:
- a. Unstable angina or myocardial infarction or coronary artery bypass graft (CABG) within 6 months prior to apheresis.
- b. New York Heart Association (NYHA) stage III or IV congestive heart failure.
- c. History of clinically significant cardiac arrhythmia (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block.
- d. History of severe nonischemic cardiomyopathy.
- e. Left ventricular ejection fraction (LVEF) \<45% as assessed by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis).
- f. Active, current cardiac manifestations of systemic lupus erythematosus (SLE) including pericarditis, pericardial effusion, and myocarditis.
- Prior history of splenectomy
- History of moderate or worse than moderate asthma or chronic obstructive pulmonary disease (COPD)
- Corrected QT interval (QTc) \>450msec in males or \>470msecs in females
- people with valvular heart disease (regurgitation, stenosis or atresia
- Moderate or worse renal impairment using criteria
- Stage 1: Kidney damage with normal or increased GFR (\>90 mL/min/1.73 m\^2).
- Stage 2: Mild reduction in GFR (60-89 mL/min/1.73 m\^2).
- Stage 3a: Moderate reduction in GFR (45-59 mL/min/1.73 m\^2).
- Stage 3b: Moderate reduction in GFR (30-44 mL/min/1.73 m\^2).
- Stage 4: Severe reduction in GFR (15-29 mL/min/1.73 m\^2).
- Stage 5: Kidney failure (GFR \< 15 mL/min/1.73 m\^2 or dialysis)
- Previously received Mavenclad, yet drug washout is ≤9 months.
- History of a seizure disorder even if the seizure disorder is well controlled with anti-epileptics
- Prior history of treatment with cellular immunotherapy (e.g. CAR T) gene therapy product directed as any target.
The study team makes the final eligibility decision.
Where it's taking place
- Palo Alto, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years to 65 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Palo Alto, California, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.