NCT07833618 - A Phase II Study of ALT001 in Patients With Amyotrophic Lateral Sclerosis (ALS) | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants or their guardians must be able to understand the procedures and methods of this study, communicate adequately with the investigator, be willing to strictly comply with the clinical trial protocol to complete the study, and voluntarily sign a written informed consent form, or have informed consent signed by a legally authorized representative. 2. Age 18 to 75 years (inclusive of both boundaries), of either sex. 3. Diagnosis of definite or probable ALS according to the revised El Escorial criteria of the World Federation of Neurology for amyotrophic lateral sclerosis, including both familial and sporadic ALS patients. 4. Forced vital capacity (FVC) ≥ 50% of predicted at the screening visit. 5. Total ALSFRS-R score ≥ 30 and ≤ 40 prior to enrollment. 6. If receiving riluzole or edaravone treatment before enrollment, participants must have been on a stable dose for ≥ 30 days prior to Day 1 of this study, and must maintain that dose until the final study visit. Exclusion Criteria: 1. Have other known diseases associated with motor neuron dysfunction that may confound or obscure the diagnosis of ALS. 2. History of alcohol dependence or drug abuse within 6 months prior to screening, judged by the investigator to be unsuitable for participation in this study. 3. Apparent cognitive impairment (MMSE scale: ≤19 for the illiterate group, ≤22 for the primary school group, and ≤26 for the junior high school and above group \[\>8 years of education\]), or other unstable psychiatric disorders that the investigator considers unsuitable for participation (including suicidal intent, untreated major depression, etc.). 4. Continuous use of non-invasive ventilation (NIV), diaphragm pacing system, or invasive ventilation (tracheostomy) at screening. 5. Severe autoimmune diseases, myeloproliferative disorders, leukemia or lymphoma, malignant tumors, fractures, or severe scoliosis at screening, which the investigator considers would affect study evaluation. 6. Other severe and/or uncontrolled major organ or unstable systemic diseases, including but not limited to uncontrolled diabetes, unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), severe congestive heart failure, uncontrolled hypertension, uncontrolled active infection, severe hepatic, renal or other severe metabolic diseases, or severe gastrointestinal diseases. 7. Positive hepatitis B surface antigen (HBsAg) with HBV-DNA \> upper limit of normal (if HBsAg is negative, HBV-DNA testing is not required); positive hepatitis C virus (HCV) antibody with HCV-RNA \> upper limit of normal (if anti-HCV is negative, HCV-RNA testing is not required); positive human immunodeficiency virus (HIV) antibody; or positive Treponema pallidum test. 8. Pregnant or lactating women, and those planning to conceive during the medication period or within 3 months after stopping the medication. 9. Participated in another interventional clinical study within 4 weeks prior to this study; received stem cell or exosome therapy within 1 year, or previously received ASO drug treatment or gene therapy. 10. Judged by the investigator to be unsuitable for participation in this study (e.g., significantly clinically significant abnormalities in physical examination or laboratory tests).

Outcomes

Primary Outcomes

Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score

The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is a validated 12-item clinician-reported scale. Total score ranges from 0 to 48, with higher scores indicating better function and lower scores indicating greater functional impairment. A higher (less negative) change from baseline indicates less functional decline.

Time frame: Baseline to Week 24 (Week0, Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24 after randomization)

Secondary Outcomes

ALSFRS-R slope from baseline to Week 24 (double-blind period)

Weekly rate of change in ALSFRS-R total score, calculated as the slope from baseline to Week 24 in the 24-week double-blind period. Higher (less negative) slope indicates slower functional decline.

Time frame: Baseline to Week 24(Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24 after randomization)

ALSFRS-R slope from baseline to Week 48 (overall study period)

Weekly rate of change in ALSFRS-R total score from baseline to Week 48, including the double-blind and open-label extension periods.

Time frame: Overall study period：Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks)

ALSFRS-R slope from Week 25 to Week 48 (open-label extension period)

The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) is a 12-item clinician-reported scale with a total score ranging from 0 to 48; higher scores indicate better function and lower scores indicate greater functional impairment. The single value reported for this outcome is the slope (rate of change) of the ALSFRS-R total score over time during the 24-week open-label extension (OLE) period, estimated by a mixed model for repeated measures using all post-baseline ALSFRS-R assessments at Weeks 25, 29, 33, 37, 41, 45, and 48. The slope is expressed as change in ALSFRS-R total score per month (points/month); a less negative slope indicates slower functional decline. Only this single slope value is reported for this outcome measure.

Time frame: Week 25 to Week 48 (Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization)

Assessment of Combined Assessment of Function and Survival (CAFS)

The Combined Assessment of Function and Survival (CAFS) is a single composite outcome that reports ONE value: the CAFS composite rank score. It aggregates two component measurements - (1) survival status and time to death or permanent assisted ventilation, and (2) change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score - using a pre-specified ranking rule: each participant is compared pairwise with every other participant, with time to death or permanent assisted ventilation taking precedence (earlier event = worse outcome) and change from baseline in ALSFRS-R total score used for participants who remain alive and free of permanent assisted ventilation (smaller decline = better outcome). The pairwise comparisons are summed to yield a single unitless CAFS composite rank score; higher scores indicate a better combined function-and-survival outcome. The component measurements are aggregated into this one reported value and are not repo

Time frame: Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks)

Assessment of ventilator-free survival (VAFS)

Time from randomization to the first occurrence of non-invasive ventilation, invasive ventilation (tracheostomy), or death due to any cause, whichever occurs first.

Time frame: Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks)

Change from baseline in forced vital capacity (FVC) /slow vital capacity (SVC) percent predictedpercent predicted

FVC expressed as percent of predicted normal value, assessed by spirometry. SVC expressed as percent of predicted normal value, assessed by spirometry.

Time frame: Baseline to Week 48 (Week 0，Week 13，Week 24, Week25，Week37，Week48)

Concentration of cytokines in serum (IFN-γ, IL-10, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-6, GRO-α, TNF-α, IL-2)

Serum concentrations of the following cytokines, measured by central laboratory assay: IFN-γ, IL-10, IL-13, IL-1β, IL-2, IL-4, IL-5, IL-6, GRO-α, TNF-α and IL-2. Concentrations are reported in pg/mL for each cytokine. This outcome measure reports laboratory analyte concentrations, not a score on a scale; therefore an unabbreviated scale title, minimum/maximum score, and score direction do not apply.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Change from baseline in ALSAQ-40 total score

The Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) is a 40-item participant-reported quality-of-life scale; each item is rated on a 5-point scale (0-4). The total score ranges from 0 to 160, with higher scores indicating worse quality of life.

Time frame: Baseline to Week 48 (Week 0，Week 1, Week 13，Week 24, Week25，Week37，Week48)

Change from baseline in ROADS total score

The Rasch-Built Overall Amyotrophic Lateral Sclerosis Disability Scale (ROADS) is a 28-item linearly weighted disability scale; each item is scored from 0 to 2, giving a raw total score range of 0-56 that is linearly transformed to a standardized total score ranging from 0 to 146. Higher scores indicate better preserved function (less disability).

Time frame: Baseline to Week 48 (Week 0，Week 1, Week 13，Week 24, Week25，Week37，Week48)

Change from baseline in modified Ashworth scale score

The Modified Ashworth Scale (MAS) is a clinician-rated scale used to assess muscle tone and spasticity during passive movement of the assessed muscle groups. Muscle tone is graded from 0 (no increase in muscle tone) to 4 (affected part rigid), with grade 1+ indicating a slight increase in tone between grades 1 and 2. The minimum score is 0 and the maximum score is 4 for each assessed muscle, with higher scores indicating greater spasticity (a worse outcome). This outcome measure reports the change from baseline in the Modified Ashworth Scale score; a positive change indicates worsening spasticity (a worse outcome).

Time frame: Baseline to Week 48 (Week 0, Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization)

Change from baseline in grip strength (kg)

Maximum hand grip strength measured by dynamometry, expressed in kilograms.

Time frame: Baseline to Week 48 (Week 0，Week 13，Week 24, Week25，Week37，Week48 )

Change from baseline in muscle strength (MRC sum score)

Manual muscle testing using the Medical Research Council (MRC) scale summed across specified muscle groups; score ranges from 0 (no contraction) to 5 (normal strength) per muscle, with a higher total sum indicating better strength.

Time frame: Baseline to Week 48 (Week 0，Week 13，Week 24, Week25，Week37，Week48 )

Change from baseline in ALS Functional Staging System stage

ALS Functional Staging System stage, assessed to characterize disease progression.

Time frame: Baseline to Week 48(Week 0，Week 13，Week 24, Week25，Week37，Week48 )

Concentration of neurofilament light chain (NfL) in plasma

Plasma NfL concentration measured by central laboratory assay.

Time frame: Week 1, Week 5, Week 9, Week 13, Week 17, Week 21, Week 24, Week 25, Week 29, Week 33, Week 37, Week 41, Week 45, Week 48 after randomization(48 weeks)

Concentration of TAR DNA-binding protein 43 (TDP-43) in plasma

Plasma TDP-43 concentration measured by central laboratory assay.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Concentration of superoxide dismutase 1 (SOD1) in plasma

Plasma SOD1 concentration measured by central laboratory assay.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Concentration of immunoglobulins in serum (IgG, IgM, IgA)

Serum concentrations of immunoglobulins measured by central laboratory assay.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Number and percentage of T-cell subsets in blood (CD3+CD4+, CD3+CD8+, CD28+, CD16+)

Enumeration of T-cell subsets by flow cytometry, including CD3+CD4+/CD3+CD8+ ratio.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Plasma proteomics profile

Proteomic profiling of plasma samples using a central laboratory platform.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Incidence of treatment-emergent anti-drug antibodies (ADA)

Number and percentage of participants with treatment-emergent ADA responses to ALT001.

Time frame: Week 1, Week 13, Week 24, Week 25, Week 37, Week48 after randomization.

Incidence of adverse events (AEs) and serious adverse events (SAEs)

Number and percentage of participants with TEAEs and SAEs, graded by NCI CTCAE version 6.0.

Time frame: From informed consent through 28 days after last dose

A Phase II Study of ALT001 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts