Tofacitinib Tested in Adults With Amyotrophic Lateral Sclerosis

Trial details

Who runs it

Beijing Tiantan Hospital

Trial code

NCT06689982

Record updated

15 November 2024

Original description

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, of which motor-neuron's degeneration may be associated with neuroinflammation. Tofacitinib is a Janus kinase (JAK) inhibitor that affects cellular hematopoiesis and cellular immune function. At the same time, tofacitinib is suitable for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This study is a single center, single arm, proof of concept, clinical trial study, and it is planned to use tofacitinib to carry out a clinical trial to observe the treatment effect of ALS patients.Read full original descriptionShow less

Tofacitinib in Patients With Amyotrophic Lateral Sclerosis: A Proof-of-concept Clinical Trials

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, of which motor-neuron's degeneration may be associated with neuroinflammation. Tofacitinib is a Janus kinase (JAK) inhibitor that affects cellular hematopoiesis and cellular immune function. At the same time, tofacitinib is suitable for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. This study is a single center, single arm, proof of concept, clinical trial study, and it is planned to use tofacitinib to carry out a clinical trial to observe the treatment effect of ALS patients.

Inclusion: 18 years old≤ age≤ 75 years old, males or females; Forced vital capacity ≥ 60% of predicted vital capacity during the screening period; The diagnosis conforms to the diagnostic criteria for amyotrophic lateral sclerosis on the Gold Coast; Based on the analysis of whether the subject significantly deviates from the baseline healthy elderly population, whole exome sequencing (WES) revealed that the embryonic lineage etiology was interpreted as CD8+ T lymphocyte group and Th1 highly activated, and patients with pathways related to neural repair and energy metabolism pathways that were not significantly inhibited;(1.Obtain genomic data of patient embryonic samples (blood or oral swab) through whole exome sequencing (WES) technology;2.Utilizing the Damage Assessment of Genome shotgun (DAGG) system developed by the Turing Darwin Laboratory team, rare coding mutations in patient genomic data are converted into an activity profile of signaling pathways (APSP). If the patient's embryonic genomic interpretation of APSP compared to the baseline healthy population's embryonic APSP shows high activation of CD8+ T lymphocyte group and Th1 activity, and non-significant inhibition of Treg, neural repair, and energy metabolism pathways, the patient may be included in the clinical trial;3.This step is analyzed by the Turing Darwin Laboratory team, and based on the entry criteria of the clinical trial (high activation of CD8+ T lymphocyte group and Th1 activity, and non-significant inhibition of Treg, neural repair, and energy metabolism pathways), a modeling setting for the APSP score threshold for ALS will be established. Patients above the threshold can be included in the trial; Subjects or their legal representatives clearly understand and voluntarily participate in the study and sign the informed consent form; Subjects (including male subjects) are willing to have no birth plan and voluntarily take effective contraceptive measures during the entire study period and within 3 months after the end of the study, and have no plan to donate sperm or eggs.

Exclusion: Patients participating in other clinical trials or using other biological agents, drugs, or devices under investigation; Serious infection; Positive HIV test or history of positive test; Positive hepatitis C virus antibody or positive test history; Lumbar spine diseases or malformation; Have other conditions known to be associated with motor neuron dysfunction that may confuse or obscure an ALS diagnosis; Other psychiatric disorders diagnosed according to DSM-V diagnostic criteria, or significant suicide intent; History of alcohol and drug abuse; Absolute lymphocyte counts < 500 cells /mm\^3, absolute neutrophil counts (ANC) < 1000 cells /mm\^3 or hemoglobin level < 9 g/dL; Hepatitis B active infection (hepatitis B surface antigen positive and/or serum HBV DNA positive or serum HBV DNA > 2 × 10\^8 IU/mL; With severe hepatic insufficiency, renal insufficiency or severe cardiac insufficiency (severe hepatic insufficiency refers to ALT value≥2.0 times the upper limit of normal value or AST value≥2.0 times the upper limit of normal value; severe renal insufficiency refers to CRE≥1.5 times the upper limit of normal value or eGFR<40mL/min/1.73m\^2; severe cardiac insufficiency refers to NYHA class 3-4); Patients who cannot cooperate with the clinical trial project cycle as determined by professional medical staff; Individual whose use of tofacitinib is forbidden; Positive syphilis test result or positive test history; Permanently dependent on ventilator-assisted ventilation; Individual who have difficulty communicating verbally to the extent that they are unable to communicate, understand or follow instructions normally, and are unable to cooperate with treatment and evaluation; Patients who are pregnant, breast-feeding, or who are likely to become pregnant and plan to become pregnant; Unable to be cooperative and complete the follow-up due to other reasons.

ClinicalTrials.gov NCT06689982