Amyotrophic Lateral Sclerosis (ALS)Phase 1NCT07875972
Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
A Phase 1 study testing Orelabrutinib in people with Amyotrophic Lateral Sclerosis (ALS), run by Liu Qing.
Trial summary
This study will evaluate the safety and tolerability of orelabrutinib in adults with amyotrophic lateral sclerosis (ALS). Orelabrutinib blocks a protein called Bruton's tyrosine kinase, which is involved in immune responses. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS)
- What is being tested?
- Orelabrutinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Oct 2028
- Phase
- 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
- Age 18 to 75 years, inclusive, regardless of sex.
- Diagnosis of amyotrophic lateral sclerosis (ALS), confirmed by a neurologist, meeting either the Gold Coast diagnostic criteria or the revised El Escorial criteria for clinically probable laboratory-supported, clinically probable, or clinically definite ALS.
- No more than 36 months from symptom onset to enrollment.
- Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score ≥35 at screening.
- Forced vital capacity (FVC) ≥70% of predicted and slow vital capacity (SVC) ≥70% of predicted, without dyspnea at rest, orthopnea, or a requirement for long-term noninvasive ventilation or supplemental oxygen.
- Ability to safely swallow the study medication as whole tablets with water at screening and before the first dose. The study medication must not be split, crushed, chewed, or dissolved for administration.
- Concomitant riluzole and/or edaravone is permitted, provided that riluzole has been administered at a stable dose for at least 30 days and/or edaravone treatment has been stable for at least one treatment cycle.
- Assessed as having full capacity to provide informed consent.
Who cannot join
- Tracheostomy or use of noninvasive ventilation (NIV) for ≥22 hours per day.
- Any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN); estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²; absolute neutrophil count (ANC) ≤1.5 × 10⁹/L; platelet count ≤100 × 10⁹/L; hemoglobin ≤100 g/L; international normalized ratio (INR) ≥1.5 times ULN; or activated partial thromboplastin time (aPTT) ≥1.5 times ULN.
- Inability to swallow or tolerate oral medication at screening.
- Current or previous malignancy.
- Known hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection, or any uncontrolled systemic infection.
- Major surgery within 6 weeks before screening or an anticipated requirement for major surgery during the study.
Show all 18Show fewer
- Current clinically significant cardiovascular disease, including New York Heart Association (NYHA) class III or IV cardiac disease, such as arrhythmia, congestive heart failure, or myocardial infarction; left ventricular ejection fraction (LVEF) <50%; primary cardiomyopathy; a history of clinically significant QTc prolongation or QTc >470 ms in females or >450 ms in males; or uncontrolled hypertension.
- A bleeding disorder, an active bleeding episode within the previous 3 months, or current use of anticoagulant or antiplatelet medication.
- Conditions that substantially affect gastrointestinal function, such as chronic diarrhea, intestinal obstruction, or previous gastrectomy.
- Any history of pulmonary fibrosis, interstitial pneumonitis, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severe pulmonary impairment.
- Previous exposure to inhibitors of the Bruton's tyrosine kinase (BTK) pathway.
- Use of strong or moderate CYP3A inhibitors or strong or moderate CYP3A inducers that cannot be safely discontinued or replaced before screening.
- Receipt of a live vaccine within the previous 2 weeks or planned receipt of a live vaccine during the study. Inactivated vaccines may be administered according to local recommendations, but vaccination dates and adverse events must be recorded.
- Drug abuse or alcohol abuse.
- Pregnancy or breastfeeding, or being a female of childbearing potential who is unwilling to use contraception during the study and for 180 days after the last dose of study medication.
- Any other clinically significant medical condition that could pose a risk to the participant, interfere with safety assessments, or increase the risk of death during the study.
- Current participation or planned participation in another investigational drug trial.
- Inability to understand the informed consent form (ICF).
About this study
Official title: Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS): A Single-Center, Open-Label, Single-Arm, Dose-Escalation Investigator-Initiated Clinical Study
This study will evaluate the safety and tolerability of orelabrutinib in adults with amyotrophic lateral sclerosis (ALS). Orelabrutinib blocks a protein called Bruton's tyrosine kinase, which is involved in immune responses. Researchers will explore how the drug acts in people with ALS and whether it affects markers of inflammation and nerve injury. Its benefit in ALS has not been established.
Participants will be observed for 12 weeks before treatment, take orelabrutinib once daily for 24 weeks, and have a follow-up visit 4 weeks after treatment. Different groups will receive 50 mg or 100 mg daily; an optional 150 mg group may open after independent review. Assessments include side effects, blood tests, daily function, breathing, and quality of life. Additional exploratory procedures are optional.
Read the detailed description
This investigator-initiated, single-center, open-label, nonrandomized pilot study uses a 3+3 dose-escalation design to evaluate oral orelabrutinib in amyotrophic lateral sclerosis (ALS). Six treated participants are initially planned, with a maximum of 18. The study comprises a 12-week run-in, 24 weeks of treatment, and 4 weeks of follow-up. Pretreatment and on-treatment functional trajectories will be compared within participants.
Sequential cohorts will receive 50 mg and 100 mg once daily. An optional 150 mg cohort requires satisfactory safety findings, pharmacokinetic/pharmacodynamic evidence suggesting inadequate target coverage, and written approval by the independent data and safety monitoring board. Escalation requires completion of the preceding cohort's 28-day dose-limiting toxicity observation and safety review.
Plasma drug sampling is scheduled before the first dose, 2 and 8 hours afterward, and before the second dose. Participants consenting to lumbar puncture may undergo paired cerebrospinal fluid and plasma sampling 2 hours after the first dose, with a 30-minute window in either direction. An optional second lumbar puncture at least 7 days after the last dose assesses biomarkers only.
Additional conditional exploratory substudies may include immune and signaling assays, blood and cerebrospinal fluid biomarkers, neurophysiology, functional magnetic resonance imaging, and positron emission tomography. These depend on consent, clinical suitability, evaluable samples or data, and technical feasibility.
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Being tested
- Orelabrutinib
- Keywords
- Amyotrophic Lateral Sclerosis, Orelabrutinib, BTK inhibitor, Neuroinflammation, Safety, Open-label
- 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.
OrelabrutinibDrug
Cohort 1 planned enrollment: 3 participants; may expand to 6 if 1/3 participants experience a dose-limiting toxicity (DLT).
Cohort 2 planned enrollment: 3 participants. This cohort will be initiated only after Cohort 1 completes the 28-day DLT observation period and the DSMB approves dose escalation.
Cohort 3 (Optional) planned enrollment: 3 participants. This cohort will be initiated only if Cohorts 1 and 2 are safe and if BTK target occupancy / PD signals suggest insufficient target coverage, with written DSMB approval.
A traditional 3+3 dose-escalation design is used,. Dose-escalation rules: If 0/3 patients experience a DLT, escalate to the next dose level; if 1/3 patients experience a DLT, expand that dose level to 6 patients; if 1/6 patients experience a DLT, escalation may proceed, whereas if ≥2/6 patients experience a DLT, the dose is deemed intolerable and escalation must stop; if ≥2/3 patients experience a DLT, escalation must stop immediately.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Orelabrutinib 50 mg QD | Experimental | Participants receive orelabrutinib 50 mg orally once daily (QD) for 24 weeks. Receives: Drug: Orelabrutinib |
| Cohort 2: Orelabrutinib 100 mg QD | Experimental | Participants receive orelabrutinib 100 mg orally once daily (QD) for 24 weeks. Receives: Drug: Orelabrutinib |
| Cohort 3 (Optional): Orelabrutinib 150 mg QD | Experimental | Optional exploratory cohort. Participants receive orelabrutinib 150 mg orally once daily (QD) for 24 weeks. Receives: Drug: Orelabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of Treatment-Emergent Adverse Events
Number and percentage of participants with at least one adverse event that begins after the first dose or worsens relative to the pretreatment condition. Severity will be graded using NCI CTCAE version 5.0, with maximum grade summarized for each participant. Events will also be summarized by relationship to study treatment.
Measured: From the first dose at Week 0 through Week 28
Incidence of Serious Adverse Events
Number and percentage of participants with at least one serious adverse event after the first dose. Seriousness is defined by death, a life-threatening event, hospitalization or prolongation of hospitalization, persistent or significant disability, congenital anomaly, or another important medical event. Seriousness is assessed separately from CTCAE severity.
Measured: From the first dose at Week 0 through Week 28
Number of Participants With Dose-Limiting Toxicities
Number of participants with at least one protocol-defined, study-drug-related DLT during the first 28 days. DLTs include specified grade 3 or higher hematologic toxicity, grade 3 or higher nonhematologic toxicity persisting for more than 7 days despite optimal supportive care, grade 3 or higher infection, a related serious adverse event, or treatment interruption totaling more than 14 days because of related adverse events.
Measured: First 28 days after the first dose
Number of Participants Who Permanently Discontinue Study Treatment Early
Number of participants who permanently stop orelabrutinib before completing the planned 24-week treatment period, regardless of reason. Reasons will be summarized. A temporary interruption alone is not permanent discontinuation.
Measured: From the first dose through Week 24
Number of Participants Who Permanently Discontinue Study Treatment Because of Adverse Events
Number of participants who permanently stop orelabrutinib before completing the planned treatment period because of an adverse event.
Measured: From the first dose through Week 24
Number of Participants With Clinically Significant Abnormalities in Safety Assessments
Number of participants with at least one new or worsened, clinically significant abnormality in protocol-specified laboratory or ancillary safety assessments after treatment begins. Assessments include hematology, chemistry, coagulation, cardiac evaluations, and infection-, bleeding-, or malignancy-related investigations. Clinical significance will be assessed by the investigator.
Measured: From the first dose at Week 0 through Week 28
Secondary outcomes (13)
Plasma Orelabrutinib Concentrations After the First Dose
Measured: Week 0: predose and 2 and 8 hours postdose; Day 2: before the second dose
CSF Orelabrutinib Concentration After the First Dose
Orelabrutinib concentration in cerebrospinal fluid (CSF), in ng/mL, measured by liquid chromatography-tandem mass spectrometry in participants who consent to and undergo the optional lumbar puncture. This is an early post-dose measurement, not a pretreatment baseline value.
Measured: Week 0: 2 hours after the first dose, with a window of plus or minus 30 minutes
CSF-to-Plasma Orelabrutinib Concentration Ratio After the First Dose
Measured: Week 0: 2 hours after the first dose, with a window of plus or minus 30 minutes
Peripheral Blood Mononuclear Cell BTK Target Occupancy
Measured: Week 0 before the first dose and Weeks 1, 4, 12, and 24
PBMC BTK Phosphorylation Level
Level of phosphorylated Bruton's tyrosine kinase (p-BTK) in peripheral blood mononuclear cells (PBMCs), assessed by immunoblotting or flow cytometry according to the prespecified laboratory method. Values will be summarized at baseline and at each follow-up visit.
Measured: Baseline (Week 0 predose) and Weeks 4, 12, and 24
Change From Baseline in Peripheral Blood B-Cell Count
Change from the predose Week 0 value in the absolute peripheral blood B-cell count, expressed as cells per microliter and measured by flow cytometry.
Measured: Baseline (Week 0 predose) and Weeks 1, 4, 12, and 24
Change From Baseline in ALSFRS-R Total Score
Change from Week 0 in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score. The scale contains 12 items and ranges from 0 to 48; higher scores indicate better function. Negative changes indicate worsening. Assessments at Weeks -12 and -6 provide additional pretreatment data for exploratory progression-slope analyses.
Measured: Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, and 28; additional pretreatment assessment at Week -12 and -6
Change From Baseline in Forced Vital Capacity Percent Predicted
Change from Week 0 in forced vital capacity (FVC), expressed as percent of the predicted value using the prespecified reference equations. Higher values indicate better respiratory function. Week 28 testing is optional.
Measured: Baseline (Week 0) and Weeks 4, 12, and 24; optional assessment at Week 28
Change From Baseline in Slow Vital Capacity Percent Predicted
Change from Week 0 in slow vital capacity (SVC), expressed as percent of the predicted value using the prespecified reference equations. Higher values indicate better respiratory function. Week 28 testing is optional.
Measured: Baseline (Week 0) and Weeks 4, 12, and 24; optional assessment at Week 28
Proportion of Participants Alive at Week 24
Measured: From the first dose through Week 24
Proportion of Participants Alive Without Severe Respiratory Insufficiency at Week 24
Proportion of participants who have experienced neither all-cause death nor severe respiratory insufficiency from treatment initiation through Week 24. Severe respiratory insufficiency is defined as tracheostomy or the use of noninvasive ventilation for at least 22 hours per day for at least 10 consecutive days.
Measured: From the first dose through Week 24
Proportion of Participants Alive Without Severe Respiratory Insufficiency or ALS-Related Hospitalization at Week 24
Proportion of participants who have experienced none of the following from treatment initiation through Week 24: all-cause death; severe respiratory insufficiency, defined as tracheostomy or the use of noninvasive ventilation for at least 22 hours per day for at least 10 consecutive days; or hospitalization due to ALS-related complications. Event dates and reasons for hospitalization will be recorded.
Measured: From the first dose through Week 24
Change From Baseline in ALSAQ-40 Summary Index
Change from Week 0 in the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) summary index. The questionnaire assesses patient-reported health status across five domains. The summary index ranges from 0 to 100; higher scores indicate worse health status. Negative changes indicate improvement.
Measured: Baseline (Week 0) and Weeks 4, 12, and 24; additional pretreatment assessment at Week -12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Liu Qing
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Liu Qing, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07875972
- Sponsor's protocol ID
- I-26PJ2099
- Status last verified
- Nov 2026
- First submitted
- 28 Sep 2026
- Last updated
- 6 Nov 2026
- 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 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS): A Single-Center, Open-Label, Single-Arm, Dose-Escalation Investigator-Initiated Clinical Study
- ClinicalTrials.gov ID
- NCT07875972
- Acronym / sponsor ID
- I-26PJ2099
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Keywords
- Amyotrophic Lateral Sclerosis, Orelabrutinib, BTK inhibitor, Neuroinflammation, Safety, Open-label
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Liu QingUniversity, hospital or other
- Study start
- Nov 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Oct 2028 (estimated)
- First posted
- 15 Oct 2026 (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.
This study will evaluate the safety and tolerability of orelabrutinib in adults with amyotrophic lateral sclerosis (ALS). Orelabrutinib blocks a protein called Bruton's tyrosine kinase, which is involved in immune responses. Researchers will explore how the drug acts in people with ALS and whether it affects markers of inflammation and nerve injury. Its benefit in ALS has not been established.
Participants will be observed for 12 weeks before treatment, take orelabrutinib once daily for 24 weeks, and have a follow-up visit 4 weeks after treatment. Different groups will receive 50 mg or 100 mg daily; an optional 150 mg group may open after independent review. Assessments include side effects, blood tests, daily function, breathing, and quality of life. Additional exploratory procedures are optional.
Detailed description
This investigator-initiated, single-center, open-label, nonrandomized pilot study uses a 3+3 dose-escalation design to evaluate oral orelabrutinib in amyotrophic lateral sclerosis (ALS). Six treated participants are initially planned, with a maximum of 18. The study comprises a 12-week run-in, 24 weeks of treatment, and 4 weeks of follow-up. Pretreatment and on-treatment functional trajectories will be compared within participants.
Sequential cohorts will receive 50 mg and 100 mg once daily. An optional 150 mg cohort requires satisfactory safety findings, pharmacokinetic/pharmacodynamic evidence suggesting inadequate target coverage, and written approval by the independent data and safety monitoring board. Escalation requires completion of the preceding cohort's 28-day dose-limiting toxicity observation and safety review.
Plasma drug sampling is scheduled before the first dose, 2 and 8 hours afterward, and before the second dose. Participants consenting to lumbar puncture may undergo paired cerebrospinal fluid and plasma sampling 2 hours after the first dose, with a 30-minute window in either direction. An optional second lumbar puncture at least 7 days after the last dose assesses biomarkers only.
Additional conditional exploratory substudies may include immune and signaling assays, blood and cerebrospinal fluid biomarkers, neurophysiology, functional magnetic resonance imaging, and positron emission tomography. These depend on consent, clinical suitability, evaluable samples or data, and technical feasibility.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Orelabrutinib 50 mg QD | Experimental | Drug: OrelabrutinibParticipants receive orelabrutinib 50 mg orally once daily (QD) for 24 weeks. |
| Cohort 2: Orelabrutinib 100 mg QD | Experimental | Drug: OrelabrutinibParticipants receive orelabrutinib 100 mg orally once daily (QD) for 24 weeks. |
| Cohort 3 (Optional): Orelabrutinib 150 mg QD | Experimental | Drug: OrelabrutinibOptional exploratory cohort. Participants receive orelabrutinib 150 mg orally once daily (QD) for 24 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 75 years, inclusive, regardless of sex.
- Diagnosis of amyotrophic lateral sclerosis (ALS), confirmed by a neurologist, meeting either the Gold Coast diagnostic criteria or the revised El Escorial criteria for clinically probable laboratory-supported, clinically probable, or clinically definite ALS.
- No more than 36 months from symptom onset to enrollment.
- Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) total score ≥35 at screening.
- Forced vital capacity (FVC) ≥70% of predicted and slow vital capacity (SVC) ≥70% of predicted, without dyspnea at rest, orthopnea, or a requirement for long-term noninvasive ventilation or supplemental oxygen.
Key exclusion criteria (18 listed)
- Tracheostomy or use of noninvasive ventilation (NIV) for ≥22 hours per day.
- Any of the following laboratory abnormalities: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN); estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m²; absolute neutrophil count (ANC) ≤1.5 × 10⁹/L; platelet count ≤100 × 10⁹/L; hemoglobin ≤100 g/L; international normalized ratio (INR) ≥1.5 times ULN; or activated partial thromboplastin time (aPTT) ≥1.5 times ULN.
- Inability to swallow or tolerate oral medication at screening.
- Current or previous malignancy.
- Known hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection, or any uncontrolled systemic infection.
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 |
|---|---|---|
| OrelabrutinibCohort 1 planned enrollment: 3 participants; may expand to 6 if 1/3 participants experience a dose-limiting toxicity (DLT). Cohort 2 planned enrollment: 3 participants. This cohort will be initiated only after Cohort 1 completes the 28-day DLT observation period and the DSMB approves dose escalation. Cohort 3 (Optional) planned enrollment: 3 participants. This cohort will be initiated only if Cohorts 1 and 2 are safe and if BTK target occupancy / PD signals suggest insufficient target coverage, with written DSMB approval. A traditional 3+3 dose-escalation design is used,. Dose-escalation rules: If 0/3 patients experience a DLT, escalate to the next dose level; if 1/3 patients experience a DLT, expand that dose level to 6 patients; if 1/6 patients experience a DLT, escalation may proceed, whereas if ≥2/6 patients experience a DLT, the dose is deemed intolerable and escalation must stop; if ≥2/3 patients experience a DLT, escalation must stop immediately. | Drug | Cohort 1: Orelabrutinib 50 mg QD, Cohort 2: Orelabrutinib 100 mg QD, Cohort 3 (Optional): Orelabrutinib 150 mg QD |
Primary outcome
Incidence and Severity of Treatment-Emergent Adverse Events
Time frame: From the first dose at Week 0 through Week 28
Number and percentage of participants with at least one adverse event that begins after the first dose or worsens relative to the pretreatment condition. Severity will be graded using NCI CTCAE version 5.0, with maximum grade summarized for each participant. Events will also be summarized by relationship to study treatment.
Incidence of Serious Adverse Events
Time frame: From the first dose at Week 0 through Week 28
Number and percentage of participants with at least one serious adverse event after the first dose. Seriousness is defined by death, a life-threatening event, hospitalization or prolongation of hospitalization, persistent or significant disability, congenital anomaly, or another important medical event. Seriousness is assessed separately from CTCAE severity.
Number of Participants With Dose-Limiting Toxicities
Time frame: First 28 days after the first dose
Number of participants with at least one protocol-defined, study-drug-related DLT during the first 28 days. DLTs include specified grade 3 or higher hematologic toxicity, grade 3 or higher nonhematologic toxicity persisting for more than 7 days despite optimal supportive care, grade 3 or higher infection, a related serious adverse event, or treatment interruption totaling more than 14 days because of related adverse events.
Number of Participants Who Permanently Discontinue Study Treatment Early
Time frame: From the first dose through Week 24
Number of participants who permanently stop orelabrutinib before completing the planned 24-week treatment period, regardless of reason. Reasons will be summarized. A temporary interruption alone is not permanent discontinuation.
Number of Participants Who Permanently Discontinue Study Treatment Because of Adverse Events
Time frame: From the first dose through Week 24
Number of participants who permanently stop orelabrutinib before completing the planned treatment period because of an adverse event.
Number of Participants With Clinically Significant Abnormalities in Safety Assessments
Time frame: From the first dose at Week 0 through Week 28
Number of participants with at least one new or worsened, clinically significant abnormality in protocol-specified laboratory or ancillary safety assessments after treatment begins. Assessments include hematology, chemistry, coagulation, cardiac evaluations, and infection-, bleeding-, or malignancy-related investigations. Clinical significance will be assessed by the investigator.
13 secondary outcomes
Plasma Orelabrutinib Concentrations After the First Dose
Time frame: Week 0: predose and 2 and 8 hours postdose; Day 2: before the second dose
CSF Orelabrutinib Concentration After the First Dose
Time frame: Week 0: 2 hours after the first dose, with a window of plus or minus 30 minutes
CSF-to-Plasma Orelabrutinib Concentration Ratio After the First Dose
Time frame: Week 0: 2 hours after the first dose, with a window of plus or minus 30 minutes
Peripheral Blood Mononuclear Cell BTK Target Occupancy
Time frame: Week 0 before the first dose and Weeks 1, 4, 12, and 24
PBMC BTK Phosphorylation Level
Time frame: Baseline (Week 0 predose) and Weeks 4, 12, and 24
Change From Baseline in Peripheral Blood B-Cell Count
Time frame: Baseline (Week 0 predose) and Weeks 1, 4, 12, and 24
Change From Baseline in ALSFRS-R Total Score
Time frame: Baseline (Week 0) and Weeks 4, 8, 12, 16, 24, and 28; additional pretreatment assessment at Week -12 and -6
Change From Baseline in Forced Vital Capacity Percent Predicted
Time frame: Baseline (Week 0) and Weeks 4, 12, and 24; optional assessment at Week 28
Change From Baseline in Slow Vital Capacity Percent Predicted
Time frame: Baseline (Week 0) and Weeks 4, 12, and 24; optional assessment at Week 28
Proportion of Participants Alive at Week 24
Time frame: From the first dose through Week 24
Proportion of Participants Alive Without Severe Respiratory Insufficiency at Week 24
Time frame: From the first dose through Week 24
Proportion of Participants Alive Without Severe Respiratory Insufficiency or ALS-Related Hospitalization at Week 24
Time frame: From the first dose through Week 24
Change From Baseline in ALSAQ-40 Summary Index
Time frame: Baseline (Week 0) and Weeks 4, 12, and 24; additional pretreatment assessment at Week -12
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 6 Nov 2026.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Orelabrutinib in people with Amyotrophic Lateral Sclerosis (ALS), run by Liu Qing.
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 8 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 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and Severity of Treatment-Emergent Adverse Events (time frame: From the first dose at Week 0 through Week 28). The study lists 6 primary outcomes in all. 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 6 Nov 2026.