Phase 2 Randomized, Double‑Blind, Placebo‑Controlled Study of TAK‑755 (recombinant ADAMTS13) in Acute Ischemic Stroke

The primary objective of this phase 2, randomized, double‑blind, placebo‑controlled trial in participants with Acute Ischemic Stroke is to assess the safety and tolerability of TAK‑755. Secondary objectives include:

• Further evaluation of safety and tolerability of TAK‑755 (Part A).
• Assessment of efficacy on functional outcome and stroke‑symptom severity versus placebo (Part A).
• Evaluation of thrombolytic efficacy based on imaging biomarkers versus placebo (Part A).
• Assessment of efficacy on functional outcome versus placebo (Part B).
• Further evaluation of efficacy on functional outcome or symptom severity versus placebo (Part B).
• Evaluation of thrombolytic efficacy using imaging markers versus placebo (Part B).

The trial enrolled 155 participants diagnosed with Acute Ischemic Stroke, encompassing both male and female individuals aged 18 to 80 years inclusive. Eligible subjects presented with a clinical diagnosis of stroke confirmed by imaging, with symptom onset occurring within 24 hours of enrollment (including wake‑up strokes where the last known well time was ≤24 hours). Inclusion required a National Institutes of Health Stroke Scale score of 6–25, indicating moderate to severe stroke, and a pre‑stroke Modified Rankin Scale score < 2, reflecting no significant prior disability. Imaging criteria mandated evidence of a causative arterial occlusion and, when available, perfusion or diffusion imaging parameters consistent with salvageable brain tissue (e.g., ASPECTS > 6, core volume < 70 cc, penumbra ≥ 10 cc). All participants provided informed consent (or consent from a legally authorized representative). The study population comprised patients meeting these clinical and radiographic thresholds, with no specific lifestyle restrictions reported; both vulnerable and non‑vulnerable adults were included. The primary objectives were to assess the safety and tolerability of TAK‑755 in Part A and Part B of the study.

The study is a randomized, double-blind, placebo-controlled Phase 2 trial evaluating the safety, tolerability, and efficacy of TAK‑755 in adults with Acute Ischemic Stroke who meet predefined imaging and clinical criteria. After an informed‑consent and screening visit to confirm eligibility, participants receive a single intravenous infusion of either the investigational product (ADZYNMA 1 500 IU) or a matching placebo. Follow‑up visits are scheduled at 24 hours, 72 hours (or discharge if earlier), Day 30, Day 60, and Day 90, during which neurological assessments, imaging, vital signs, laboratory tests, and adverse‑event monitoring are performed. The primary endpoint is the proportion of participants experiencing symptomatic intracranial hemorrhage within 120 hours post‑infusion, with secondary endpoints including functional outcomes (modified Rankin Scale, NIHSS), recanalization, reperfusion, infarct volume, and safety parameters up to 90 days. Participant involvement spans approximately three months from enrollment to the end‑of‑study visit at Day 90. Early termination may occur if a participant develops a prespecified severe adverse event, experiences symptomatic intracranial hemorrhage, violates major protocol criteria, or withdraws consent.

The investigational product is identified as ADZYNMA 1 500 IU powder reconstituted with solvent to produce a solution for injection. Each administered dose contains 500 IU of the recombinant protein RADAMTS13, delivered by intravenous infusion. The formulation is supplied as a sterile solution intended for single‑dose administration; the exact frequency of dosing (e.g., once daily or single infusion) follows the study protocol and is recorded for each participant.

The control arm utilizes a lyophilized product that matches the appearance and functional characteristics of TAK-755. This placebo is reconstituted in an identical manner to the active product and administered by the same intravenous route to preserve blinding. No active pharmaceutical ingredient is present in the placebo preparation.

All study drug administrations are performed in a clinical setting under controlled conditions. Dosing times, infusion rates, and total administered volumes are documented in the source data record. Compliance monitoring includes verification of infusion completion, assessment of any deviations from the prescribed schedule, and recording of infusion‑related observations in the case report form.

Efficacy will be evaluated using several clinical and imaging endpoints. Functional outcome will be measured by the modified Rankin Scale (mRS) with the proportion of participants achieving scores of 0‑1 and 0‑2 assessed at Day 90, and the ordinal distribution of mRS at the same time point. Neurological deficit will be quantified by the change from baseline in the National Institutes of Health Stroke Scale (NIHSS) score at 24 hours post‑intervention. Revascularization will be assessed at 24 hours by determining complete recanalization using an arterial occlusive lesion (AOL) score of 3, and by measuring reperfusion defined as a >90 % reduction in the volume of reversible ischemic tissue (penumbra) from baseline. Final infarct volume will be recorded at 72 hours or at hospital discharge, whichever occurs first.

These parameters will be collected using validated clinical scales (mRS, NIHSS, AOL) and standard neuroimaging techniques for infarct volumetry. Data will be analyzed by comparing the proportion of participants achieving each predefined outcome between the test and placebo groups, and by evaluating the magnitude of change in continuous measures such as NIHSS score and infarct volume.