About this trial

This is a phase II, randomized, double-blind, placebo-controlled, multicentre clinical study to evaluate the efficacy and safety of ALT001 in patients with ischemic stroke in the sequelae stage (≥180 days and ≤5 years after the most recent event). A total of 200 participants will be randomized 1:1:1:1 to receive ALT001 at 65 μg/day, 130 μg/day, or 260 μg/day, or matching placebo, by intravenous infusion once daily (over \~60 minutes) using a 14-day-on / 14-day-off cycle for 3 cycles (12 weeks) in the double-blind (DB) period, followed by an optional open-label extension (OLE) period of 3 additional cycles. The primary endpoint is the change from baseline in the Fugl-Meyer Assessment (FMA) motor score at Week 12.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male or female participants aged 18 to 80 years, inclusive (determined at the time of signing the informed consent form);

A history of acute ischemic stroke confirmed by CT or MRI, with the most recent stroke occurring ≥180 days and no more than 5 years prior to enrollment;

Unilateral limb weakness, with a total Fugl-Meyer Motor score ≤90;

Modified Ashworth Scale score ≤2;

Disqualifiers

The culprit lesion of the most recent stroke is a posterior circulation infarct on imaging;

Baseline head CT or MRI showing malformations, tumors, abscesses, or other major non-vascular brain diseases (e.g., multiple sclerosis, dementia, Parkinson's disease, and other neurodegenerative diseases);

A cerebrovascular or cardiovascular event within the past 3 months, such as transient ischemic attack (TIA) or acute coronary syndrome (ACS);

History of recurrent seizures or epilepsy;

Trial design

Design model

Parallel

Treatments tested in this trial

ALT001
Drug
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.
Placebo (ALT001 matching placebo)
Other intervention
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).

Treatment groups

200 Participants

are divided into 4 treatment groups

Group A: ALT001 65 μg/dayExperimental treatment 1 intervention

Group B: ALT001 130 μg/dayExperimental treatment 1 intervention

Group C: ALT001 260 μg/dayExperimental treatment 1 intervention

Group D: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Change from baseline in Fugl-Meyer Assessment (FMA) motor score

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.

Time frame

Week 12 (double-blind period)

Secondary outcomes

1

Change from baseline in the Fugl-Meyer Assessment (FMA) Motor score

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.

Time frame

After 4 and 8 weeks of treatment during the double-blind treatment period

2

Change from baseline in modified Rankin Scale (mRS) distribution / proportion of patients by mRS grade

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.

Time frame

Weeks 4, 8, and 12

3

Change from baseline in National Institutes of Health Stroke Scale (NIHSS) score

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).

Time frame

Weeks 4, 8, and 12

4

Change from baseline in Barthel Index (BI) score

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).

Time frame

Weeks 4, 8, and 12

Other outcomes

1

Incidence of new-onset vascular events (new-onset stroke, myocardial infarction, and vascular death)

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.

Time frame

From first dose through study completion, up to approximately 28 weeks (up to 24 weeks of treatment, comprising the 12-week double-blind period and the 12-week open-label extension period, plus a 28-day post-treatment safety follow-up).

2

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

Baseline and Week 12 (double-blind period); Week 12 and Week 24 (open-label extension period)

3

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

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.

Time frame

Baseline and Week 12 (double-blind period); Week 12 and Week 24 (open-label extension period)

4

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

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.

Time frame

Baseline and Week 12 (double-blind period); Week 12 and Week 24 (open-label extension period)

ALT001 in Patients With Ischemic Stroke in the Sequelae Stage

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

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