Tofacitinib in Patients With Amyotrophic Lateral Sclerosis

NCT06689982 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: KY2024-144-02
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic lateral sclerosis; Clinical trial; Tofacitinib; Neuroinflammation

Outcome Measures

Primary Outcomes (1)

• Changes of ALSFRS-R scale scores in ALS patients

  Amyotrophiclateral sclerosis functional rating scale revised(ALSFRS-R) is the most common evaluation indicator in ALS related research, with scores ranging from 0 to 48. The higher the score, the better the functional retention and the milder the symptoms.

  day 180±14

Secondary Outcomes (6)

• Incidence of invasive mechanical ventilation in ALS patients

  180 days

• Changes of modified Norris scale scores in ALS patients

  day 30±3, 90±7, and 180±14

• Changes of ALSAQ-40 scale scores in ALS patients

  baseline, day 30±3, day 90±7, and day180±14

• Changes in EQ-5D-5L scale scores in ALS patients

  baseline, day 30±3, day 90±7, and day180±14

• Changes of lung function in ALS patients

  baseline, day 30±3, day 90±7, and day180±14

Other Outcomes (24)

• Changes of muscle strength in ALS patients

  baseline, day 30±3, day 90±7, and day180±14

• Changes of gait function in ALS patients

  baseline, day 30±3, day 90±7, and day180±14

• Changes of 7T MRI imaging indicators in ALS patients

  baseline, day 30±3, day 90±7, and day180±14

Study Arms (1)

Tofacitinib

EXPERIMENTAL

This group will receive tofacitinib citrate sustained-release tablets at 180 consecutive days .

Drug: Tofacitinib tablets

Interventions

Tofacitinib tablets DRUG

All patients should be closely monitored for signs and symptoms of infection during and after treatment with tofacitinib tablets. If a patient develops a severe infection, opportunistic infection, or sepsis, medication should be discontinued. During treatment, patients with lymphocyte counts \< 500 cells/mm\^3 or ANC \< 500 cells/mm\^3 confirmed by repeated testing should be stopped. When 500≤ANC≤1000 cells/mm\^3, administration should be interrupted, and if ANC returns to more than 1000 cells/mm\^3, administration should be resumed. When hemoglobin \< 8 g/dL or decreases by more than 2 g/dL, administration should be interrupted until hemoglobin values return to normal.

Tofacitinib

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Hepatitis B active infection (hepatitis B surface antigen positive and/or serum HBV DNA positive or serum HBV DNA \> 2 × 10\^8 IU/mL;
• Positive syphilis test result 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;
• 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);
• 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;
• History of alcohol and drug abuse;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead
• Turing-Darwin Laboratory; West Institute of Computing Technology, Chongqing, China: collaborator

Study Sites (1)

Beijing Tiantan Hospital

Beijing, 100050, China

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Neuroinflammatory Diseases

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Yilong Wang, PhD+MD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yilong Wang, PhD+MD

CONTACT

0086-010-67092222; yilong528@aliyun.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Model Details: tofacitinib (5mg per tablet)

Study Record Dates

• First Submitted: July 22, 2024
• First Posted: November 15, 2024
• Study Start: December 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: June 1, 2026
• Last Updated: November 15, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)