ALT001 in Patients With Ischemic Stroke in the Sequelae Stage

A total of 50 participants in the active treatment arm. ALT001 65 μg/day (~1.0 μg/kg), reconstituted in 100 mL normal saline, IV infusion once daily over ~60 minutes; 14 days on / 14 days off per cycle; 3 cycles in DB period.

A total of 150 participants in the active treatment arm were randomized in a 1:1:1 ratio to the 65 μg/day ALT001 treatment group, the 130 μg/day ALT001 treatment group, or the 260 μg/day ALT001 treatment group, with 50 participants in each group. For each treatment group, according to the assigned dose, ALT001 was dissolved in 100 mL of normal saline injection and administered by intravenous infusion once daily, completed within approximately 60 minutes.

Dosing schedule: Fourteen days of continuous dosing followed by 14 days off constituted one cycle. The DB period consisted of 3 consecutive cycles, Participants who complete the DB period will enter the OLE treatment period, using the same administration method as in the DB period. The active treatment groups will continue to receive the dose level of their assigned dose group, and the OLE period consisted of 3 consecutive cycles.

A total of 50 participants in the active treatment arm. ALT001 130 μg/day (~2.0 μg/kg), same administration schedule as Arm 1.

A total of 150 participants in the active treatment arm were randomized in a 1:1:1 ratio to the 65 μg/day ALT001 treatment group, the 130 μg/day ALT001 treatment group, or the 260 μg/day ALT001 treatment group, with 50 participants in each group. For each treatment group, according to the assigned dose, ALT001 was dissolved in 100 mL of normal saline injection and administered by intravenous infusion once daily, completed within approximately 60 minutes.

Dosing schedule: Fourteen days of continuous dosing followed by 14 days off constituted one cycle. The DB period consisted of 3 consecutive cycles, Participants who complete the DB period will enter the OLE treatment period, using the same administration method as in the DB period. The active treatment groups will continue to receive the dose level of their assigned dose group, and the OLE period consisted of 3 consecutive cycles.

A total of 50 participants in the active treatment arm. ALT001 260 μg/day (~4.0 μg/kg), same administration schedule as Arm 1.

A total of 150 participants in the active treatment arm were randomized in a 1:1:1 ratio to the 65 μg/day ALT001 treatment group, the 130 μg/day ALT001 treatment group, or the 260 μg/day ALT001 treatment group, with 50 participants in each group. For each treatment group, according to the assigned dose, ALT001 was dissolved in 100 mL of normal saline injection and administered by intravenous infusion once daily, completed within approximately 60 minutes.

Dosing schedule: Fourteen days of continuous dosing followed by 14 days off constituted one cycle. The DB period consisted of 3 consecutive cycles, Participants who complete the DB period will enter the OLE treatment period, using the same administration method as in the DB period. The active treatment groups will continue to receive the dose level of their assigned dose group, and the OLE period consisted of 3 consecutive cycles.

ALT001 matching placebo (simulator) without active ingredient, same administration schedule; in the OLE period, placebo-group participants are re-randomized to one of the three active dose groups for 3 cycles (12 weeks).

The placebo group consisted of 50 participants. The placebo was dissolved in 100 mL of normal saline injection and administered by intravenous infusion once daily, completed within approximately 60 minutes.

Dosing schedule: Fourteen days of continuous dosing followed by 14 days off constituted one cycle. The DB period consisted of 3 consecutive cycles, and the OLE period consisted of 3 consecutive cycles.

Participants who complete the DB period will enter the OLE treatment period. The placebo group will be randomly assigned to the 3 dose groups and receive treatment for 3 consecutive cycles (12 weeks).

The Fugl-Meyer Assessment (FMA) is used to evaluate the motor function of patients with ischemic stroke. It comprises an upper-extremity motor function subscore (66 points) and a lower-extremity motor function subscore (34 points), for a total of 100 points. Total-score grading: 0-49 = severe motor impairment; 50-84 = marked motor impairment; 85-95 = moderate motor impairment; 96-99 = mild motor impairment.

The Fugl-Meyer Assessment (FMA) is used to evaluate the motor function of patients with ischemic stroke. It comprises an upper-extremity motor function subscore (66 points) and a lower-extremity motor function subscore (34 points), for a total of 100 points. Total-score grading: 0-49 = severe motor impairment; 50-84 = marked motor impairment; 85-95 = moderate motor impairment; 96-99 = mild motor impairment.

The modified Rankin Scale (mRS) is a global outcome measure of disability and functional independence after stroke, graded on an ordinal scale from 0 to 6: 0 = no symptoms, 1 = no clinically significant disability, 2 = slight disability, 3 = moderate disability (requires some help), 4 = moderately severe disability (unable to walk unassisted), 5 = severe disability (bedridden, requiring constant care), and 6 = death. The mRS score range is 0 to 6; higher scores indicate worse outcome (greater disability). The proportion of patients in each mRS grade and the shift in mRS distribution from baseline will be summarized at Weeks 4, 8, and 12.

Difference in NIHSS score from baseline to Weeks 4, 8, and 12 of the double-blind treatment period. The National Institutes of Health Stroke Scale (NIHSS) is an ordinal scale used to quantify neurological impairment in stroke patients, assessing 11 domains including level of consciousness, gaze, visual fields, facial palsy, motor function of the arms and legs, limb ataxia, sensory loss, language (aphasia), dysarthria, and inattention (extinction/inattention). The NIHSS score range is 0 to 42, with lower scores indicating less severe neurological impairment. Higher scores indicate worse outcome (more severe neurological deficit).

Difference in Barthel Index (BI) score from baseline to Weeks 4, 8, and 12 of the double-blind treatment period. The Barthel Index (BI) is an ordinal scale that measures functional independence in activities of daily living (ADL), assessing 10 items: feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers, mobility, and stairs. Each activity is scored on a 5-level scale, with level 1 being the lowest and level 5 the highest. A higher level indicates a greater degree of independence. The BI score range is 0 to 100, with higher scores indicating better outcome (greater independence in daily living).

The Modified Ashworth Scale (MAS) is used to assess muscle tone and degree of spasticity during passive movement of skeletal muscles; the investigator performs passive stretching of the target muscle group and grades the increase in tone and resistance to passive movement. Scoring ranges from grade 0 to grade 4, with grade 1+ indicating a slight increase in tone with resistance intermediate between grade 1 and grade 2 (numeric range 0 to 4). Higher scores indicate worse outcome (more severe spasticity). In this study, six movements are assessed separately: upper limb - elbow flexion, wrist flexion, forearm pronation; lower limb - knee extension, knee flexion, ankle plantar flexion. Assessed once per cycle during the 3-cycle OLE period.

Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), summarized by system organ class and preferred term (MedDRA coded), and graded according to CTCAE v5.0. Events are collected from the first dose of study drug through the 28-day post-treatment safety follow-up and reported for the double-blind period, the open-label extension period, and the overall treatment period.

New-onset stroke, myocardial infarction, and vascular death occurring from first dose through the 28-day post-treatment follow-up will be adjudicated/confirmed by [the investigator and/or an independent endpoint adjudication committee] and reported as number and percentage of participants with each event type in each dose group.

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.

Serum concentrations of immunoglobulins IgG, IgM, and IgA measured by central laboratory assay, reported in mg/dL for each immunoglobulin. This outcome measure reports laboratory analyte concentrations, not a score on a scale.

Enumeration of T-cell subsets (CD3+CD4+, CD3+CD8+, CD28+, CD16+) by flow cytometry, reported as cell counts and percentages of lymphocytes, including the CD3+CD4+/CD3+CD8+ ratio. This outcome measure reports cell counts/percentages, not a score on a scale.

Number and percentage of participants with treatment-emergent anti-drug antibody (ADA) responses to ALT001, measured by central laboratory assay; ADA titre is reported where applicable. This outcome measure reports incidence and titre, not a score on a scale.

The modified Rankin Scale (mRS) is a global outcome measure of disability and functional independence after stroke, graded on an ordinal scale from 0 to 6: 0 = no symptoms, 1 = no clinically significant disability, 2 = slight disability, 3 = moderate disability (requires some help), 4 = moderately severe disability (unable to walk unassisted), 5 = severe disability (bedridden, requiring constant care), and 6 = death. The mRS score range is 0 to 6; higher scores indicate worse outcome (greater disability).

The National Institutes of Health Stroke Scale (NIHSS) is an ordinal scale used to quantify neurological impairment in stroke patients, assessing 11 domains including level of consciousness, gaze, visual fields, facial palsy, motor function of the arms and legs, limb ataxia, sensory loss, language (aphasia), dysarthria, and inattention (extinction/inattention). The NIHSS score range is 0 to 42, with lower scores indicating less severe neurological impairment. Higher scores indicate worse outcome (more severe neurological deficit).

The Barthel Index (BI) is an ordinal scale that measures functional independence in activities of daily living (ADL), assessing 10 items: feeding, bathing, grooming, dressing, bowel control, bladder control, toilet use, transfers, mobility, and stairs. Each activity is scored on a 5-level scale, with level 1 being the lowest and level 5 the highest. A higher level indicates a greater degree of independence. The BI score range is 0 to 100, with higher scores indicating better outcome (greater independence in daily living).

The Modified Ashworth Scale (MAS) is used to assess muscle tone and degree of spasticity during passive movement of skeletal muscles; the investigator performs passive stretching of the target muscle group and grades the increase in tone and resistance to passive movement. Scoring ranges from grade 0 to grade 4, with grade 1+ indicating a slight increase in tone with resistance intermediate between grade 1 and grade 2 (numeric range 0 to 4). Higher scores indicate worse outcome (more severe spasticity). In this study, six movements are assessed separately: upper limb - elbow flexion, wrist flexion, forearm pronation; lower limb - knee extension, knee flexion, ankle plantar flexion. Assessed once per cycle during the 3-cycle OLE period.

The Fugl-Meyer Assessment (FMA) evaluates motor function in patients with ischemic stroke and comprises an upper-extremity motor subscore (0 to 66) and a lower-extremity motor subscore (0 to 34), for a total score range of 0 to 100. Per the protocol's total-score grading: 0-49 = severe, 50-84 = marked, 85-95 = moderate, 96-99 = mild motor impairment. Higher scores indicate better motor function.