Amyotrophic Lateral Sclerosis
Conditions
Interventions
Experimental Group:Study participants were assigned to two or three consecutive dose cohorts. Dose group 1 was 10mg, dose group 2 was 20mg, and dose group 3 was 30 or 40mg. Each dose cohort will first
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Men or women who were >= 18 and <= 75 years of age at the first screening visit. The investigators believed that the study participants could and were willing to meet all trial requirements, including traveling to the trial center, following the procedures specified in the protocol, completing all measurements, and attending planned visits. 7. Before the first screening visit, participants who received a stable dose of the approved ALS drug for at least 4 weeks or without such drug treatment. a. If treated with riluzole: The study participants must receive a stable dose (e.g., BID 50 mg) and are expected to maintain this dose until the final trial visit. b. If treated with edaravone: The study participants must have completed at least 2 treatment cycles before the screening period and are expected to maintain a stable dose until the follow-up end-of-trial (EoF) visit. For study participants receiving IV edaravone treatment, edaravone administration and TRCN-1023 administration must be spaced at least 1 week apart. 8. Participants were not previously exposed to any other unapproved drugs and had no planned use during the study. 9. Screening values of coagulation parameters (including platelet count, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT)) should be within the normal range. If the coagulation parameters exceed the range, but the investigators consider it clinically insignificant, the parameter can be re-tested once. If the values exceeding the range persist, but the investigators consider the study participants suitable for inclusion, the investigators should consult the principal investigator. Note that platelet count must reach 100,000/mm^3 or above to be eligible. 10. Female study participants: a. Study participants with reproductive capacity must agree to use at least one highly effective contraceptive method from the time of signing the informed consent until the final administration of TRCN-1023, with the expected plasma concentration of TRCN-1023 being below the detection limit by the end of the study. b. Post-menopausal status (defined as having ceased menstruation for at least 12 months prior to the first screening visit, and without any other medical reasons), and confirmed at the first screening visit through FSH measurement results (if the duration of amenorrhea does not reach 12 months, it must be confirmed by two FSH measurement results within the post-menopausal range). c. Had undergone surgical sterilization (i.e., hysterectomy, bilateral tubal resection, or bilateral oophorectomy) at least 1 month before the first screening visit. d.2. Diagnosed as clinically confirmed, clinically probable, or laboratory-supported clinically probable ALS according to the revised EI Escorial World Federation of Neurology criteria. (3) Disease duration <=24 months, disease onset time was defined as the first onset of muscle weakness and/or upper motor neuron dysfunction, including fasciculation and/or painful spasms. At the first screening visit, slow vital capacity (SVC) was measured in a seated position. This assessment can be repeated up to five times until three technically acceptable results are obtained. The best value, adjusted for age, sex, and height, had to be 60% or more of the predicted value. 5. The first five participants at each dose level were enrolled with unlimited genotypes, with the exclusion of individuals with ALS-associated SOD1 and FUS variant
Exclusion criteria
Exclusion criteria: 1. Confirmed carriers of pathogenic or likely pathogenic SOD1 and FUS gene mutations. 2. Tracheostomy anytime, or continuous assisted ventilation of any type during the preceding 3 months before the first Screening Visit. 3. Significant pulmonary disorder not attributed to ALS, which may complicate the evaluation of the respiratory function. Intermittent non-invasive ventilation is permitted. 4. Use of a diaphragm pacemaker. 5. Speech or communication difficulties precluding normal communication, comprehension or adherence to instructions, or cooperation with treatment and assessments. 6. Any known history of other medical conditions associated with motor neuron dysfunction that could confound the clarity of the ALS diagnosis. 7. Pregnant or breast-feeding females; or females with childbearing potential if no adequate contraceptive measures are used. 8. Any contraindication to brain MRI scans, including presence of claustrophobia, pacemakers, aneurysm clips, artificial heart valves, implants, metal fragments, or foreign objects in the eyes, skin, or body that constitute a contraindication to having a brain MRI scan. 9. Any contraindication to lumbar puncture, IT injections, including but not limited to: a. Clinically relevant thrombocytopenia (platelet count 3 × upper limit of normal [ULN]). Of note: An elevation of AST only (>3 × ULN) with normal se
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation; | — |
Secondary
| Measure | Time frame |
|---|---|
| General demographic measures and clinical data;Collection of laboratory data;Imaging examination;Repetitive neural stimulation;Clinical efficacy and function evaluation;Collection of other information;Electrocardiogram; | — |
Countries
China
Contacts
Public ContactYilong Wang
Beijing Tiantan Hospital, Capital Medical University
Outcome results
None listed