Amyotrophic Lateral SclerosisEarly Phase 1TALENTNCT06689982
Tofacitinib in Patients With Amyotrophic Lateral Sclerosis
A Early Phase 1 study testing Tofacitinib tablets in people with Amyotrophic Lateral Sclerosis, run by Beijing Tiantan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- Tofacitinib tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 1 Dec 2024to 1 Jun 2026
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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;
- Patients who are pregnant, breast-feeding, or who are likely to become pregnant and plan to become pregnant;
- Patients participating in other clinical trials or using other biological agents, drugs, or devices under investigation;
- Unable to be cooperative and complete the follow-up due to other reasons.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
Read the detailed description
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive loss and dysfunction of upper and lower motor neurons located in the brain and spinal cord, further resulting in paralysis. In the occurrence and development of ALS, the degeneration of motor neurons may be related to neuroinflammatory response, often accompanied by excessive proliferation of microglia, astrocyte and oligodendrocyte. Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes that transport signals generated by cytokine or growth factor-receptor interactions on cell membranes, thereby influencing cellular hematopoietic processes and cellular immune function. At the same time, tofacitinib is a marketed drug suitable for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this study, tofacitinib was selected to carry out a clinical randomized controlled trial to observe the treatment effect in ALS patients.
This study is a single center, single arm, proof of concept, clinical trial study. In this study, 12 patients will be enrolled. The treatment will be 1 tablet (5 mg) twice a day, and be administered continuously for a total of 180 days.
Follow up: Face to face interviews will be made on baseline, 30±3 days, 90±7 days, and 180±14 days.
The primary outcome measure was the difference of changes in ALSFRS-R scale scores at 30±3 days, 90±7 days, and 180±14 days from baseline.
Secondary outcomes included the incidence of invasive mechanical ventilation within 180 days , the changes in modified Norris scale scores, quality of life (ALSAQ-40, EQ-5D-5L), lung function, and electromyography indicators at 30±3 days, 90±7 days, and 180±14 days from baseline.
Exploratory outcomes included the changes in muscle strength, gait function, 7T-MRI imaging indicators, biomarkers in plasma and CSF, fatigue level, anxious level and depressive level, constipation clinical score, overactive bladder symptom score and CNS-BFS score at 30±3 days, 90±7 days, and 180±14 days from baseline; clinical progression within 180 days; the relationship between embryological etiology of ALS patients and the severity and progression in ALS patients, as well as the multiple group changes in ALS patients during disease progression.
Safe outcomes included the incidence in adverse event/severe adverse event, death, serious infection, malignant tumor, lymphoproliferative disease, major cardiovascular adverse events, thrombogenesis, abnormal lymphocytes and neutrophilic granuloaytopenia within 180 days.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- Tofacitinib tablets
- Keywords
- Amyotrophic lateral sclerosis, Clinical trial, Tofacitinib, Neuroinflammation
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tofacitinib tabletsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Tofacitinib | Experimental | This group will receive tofacitinib citrate sustained-release tablets at 180 consecutive days . Receives: Drug: Tofacitinib tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day 180±14
Secondary outcomes (6)
Incidence of invasive mechanical ventilation in ALS patients
The incidence of invasive mechanical ventilation in ALS patients.
Measured: 180 days
Changes of modified Norris scale scores in ALS patients
The changes of modified Norris scale scores in ALS patients from baseline. The modified Norris scale is a self-assessment scale for ALS patients, with scores ranging from 0 to 120, with higher scores indicating better functional retention.
Measured: day 30±3, 90±7, and 180±14
Changes of ALSAQ-40 scale scores in ALS patients
The changes of ALSAQ-40 scale scores in ALS patients from baseline. The scale is an evaluation of the quality of life of ALS patients, with indicators including physical activity, dietary ability, social interaction ability, and emotional response. Simple and highly operable, it can be used for patients to self evaluate their quality of life, with scores ranging from 0 to 200. The higher the score, the milder the symptoms.
Measured: baseline, day 30±3, day 90±7, and day180±14
Changes in EQ-5D-5L scale scores in ALS patients
The changes of EQ-5D-5L scale scores in ALS patients from baseline. It includes five dimensions(mobility, self-care, usual activities, pain/discomfort, anxiety/depression), and each dimension contains five levels of severity - no problem, minor problem, moderate problem, serious problem, extremely serious problem.
Measured: baseline, day 30±3, day 90±7, and day180±14
Changes of lung function in ALS patients
The changes of lung function (forced vital capacity) in ALS patients from baseline. Value decline indicates worse outcome of ALS patients, or disease progression and disability.
Measured: baseline, day 30±3, day 90±7, and day180±14
Changes of electromyography indicators in ALS patients
The changes of electromyography indicators in ALS patients from baseline. Muscle involvement will be assessed by needle electromyography, which analyzes muscle damage qualitatively based on spontaneous, motor unit action potential and recruitment. More muscle involvement indicates worse outcome of ALS patients, or disease progression and disability. The electromyographic indicators include the amplitude of CMAP, munix, and musix of different muscles.
Measured: baseline, day 30±3, day 90±7, and day180±14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2024
- Study start1 Dec 2024 (estimated)
- Primary completion1 Dec 2025 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- More trials run by Beijing Tiantan HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- tofacitinib (5mg per tablet)
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Tiantan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Turing-Darwin Laboratory; West Institute of Computing Technology, Chongqing, China
- Responsible party
- Principal investigator, yilong Wang, Beijing Tiantan Hospital
- Investigators
- Yilong Wang, PhD+MD, Principal investigator, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06689982
- Sponsor's protocol ID
- KY2024-144-02
- Acronym
- TALENT
- Status last verified
- Nov 2024
- First submitted
- 22 Jul 2024
- Last updated
- 15 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tofacitinib in Patients With Amyotrophic Lateral Sclerosis: A Proof-of-concept Clinical Trials
- ClinicalTrials.gov ID
- NCT06689982
- Acronym / sponsor ID
- TALENT / KY2024-144-02
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Amyotrophic lateral sclerosis, Clinical trial, Tofacitinib, Neuroinflammation
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Beijing Tiantan HospitalUniversity, hospital or other
- Collaborators
- Turing-Darwin Laboratory; West Institute of Computing Technology, Chongqing, China
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Dec 2025 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 15 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Amyotrophic lateral sclerosis is a fatal neurodegenerative disease characterized by progressive loss and dysfunction of upper and lower motor neurons located in the brain and spinal cord, further resulting in paralysis. In the occurrence and development of ALS, the degeneration of motor neurons may be related to neuroinflammatory response, often accompanied by excessive proliferation of microglia, astrocyte and oligodendrocyte. Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes that transport signals generated by cytokine or growth factor-receptor interactions on cell membranes, thereby influencing cellular hematopoietic processes and cellular immune function. At the same time, tofacitinib is a marketed drug suitable for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this study, tofacitinib was selected to carry out a clinical randomized controlled trial to observe the treatment effect in ALS patients.
This study is a single center, single arm, proof of concept, clinical trial study. In this study, 12 patients will be enrolled. The treatment will be 1 tablet (5 mg) twice a day, and be administered continuously for a total of 180 days.
Follow up: Face to face interviews will be made on baseline, 30±3 days, 90±7 days, and 180±14 days.
The primary outcome measure was the difference of changes in ALSFRS-R scale scores at 30±3 days, 90±7 days, and 180±14 days from baseline.
Secondary outcomes included the incidence of invasive mechanical ventilation within 180 days , the changes in modified Norris scale scores, quality of life (ALSAQ-40, EQ-5D-5L), lung function, and electromyography indicators at 30±3 days, 90±7 days, and 180±14 days from baseline.
Exploratory outcomes included the changes in muscle strength, gait function, 7T-MRI imaging indicators, biomarkers in plasma and CSF, fatigue level, anxious level and depressive level, constipation clinical score, overactive bladder symptom score and CNS-BFS score at 30±3 days, 90±7 days, and 180±14 days from baseline; clinical progression within 180 days; the relationship between embryological etiology of ALS patients and the severity and progression in ALS patients, as well as the multiple group changes in ALS patients during disease progression.
Safe outcomes included the incidence in adverse event/severe adverse event, death, serious infection, malignant tumor, lymphoproliferative disease, major cardiovascular adverse events, thrombogenesis, abnormal lymphocytes and neutrophilic granuloaytopenia within 180 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- tofacitinib (5mg per tablet)
| Arm | Type | Receives |
|---|---|---|
| Tofacitinib | Experimental | Drug: Tofacitinib tabletsThis group will receive tofacitinib citrate sustained-release tablets at 180 consecutive days . |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (18 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tofacitinib tabletsAll 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. | Drug | Tofacitinib |
Primary outcome
Changes of ALSFRS-R scale scores in ALS patients
Time frame: day 180±14
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.
6 secondary outcomes
Incidence of invasive mechanical ventilation in ALS patients
Time frame: 180 days
Changes of modified Norris scale scores in ALS patients
Time frame: day 30±3, 90±7, and 180±14
Changes of ALSAQ-40 scale scores in ALS patients
Time frame: baseline, day 30±3, day 90±7, and day180±14
Changes in EQ-5D-5L scale scores in ALS patients
Time frame: baseline, day 30±3, day 90±7, and day180±14
Changes of lung function in ALS patients
Time frame: baseline, day 30±3, day 90±7, and day180±14
Changes of electromyography indicators in ALS patients
Time frame: baseline, day 30±3, day 90±7, and day180±14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yilong Wang, PhD+MD principal investigator
Beijing Tiantan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Tofacitinib tablets in people with Amyotrophic Lateral Sclerosis, run by Beijing Tiantan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yilong Wang, PhD+MD (0086-010-67092222 ext. 0, yilong528@aliyun.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes of ALSFRS-R scale scores in ALS patients (time frame: day 180±14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.