NCT06689982
Tofacitinib in Patients With Amyotrophic Lateral Sclerosis
Not Yet Recruiting · Early Phase 1 · Beijing Tiantan Hospital · registry updated 2024-11-15
Inclusion and exclusion lines below are quoted from ClinicalTrials.gov. No match score is shown, because a score needs a person's age, biomarkers, and treatment dates. Confirm the record with the study team.
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
- 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 who cannot cooperate with the clinical trial project cycle as determined by professional medical staff;
- Individual whose use of tofacitinib is forbidden;
- Absolute lymphocyte counts \< 500 cells /mm\^3, absolute neutrophil counts (ANC) \< 1000 cells /mm\^3 or hemoglobin level \< 9 g/dL;
- Serious infection;
- Positive HIV test or history of positive test;
- Positive hepatitis C virus antibody or positive test history;