Preliminary results of overseas Phase III clinical study for ART-123
Asahi Kasei Pharma Corp.
Asahi Kasei Pharma›s subsidiary Asahi Kasei Pharma America Corp. has obtained preliminary results of its Phase III clinical study (SCARLET) of ART-123 (generic name: recombinant thrombomodulin alfa; marketed as Recomodulin™ in Japan) for the treatment of severe sepsis with coagulopathy.
The SCARLET study was performed as a randomized, double-blind, placebo-controlled, multinational Phase III clinical study to assess the safety and efficacy of ART-123 for 800 patients having severe sepsis with coagulopathy in North and South America, Europe, Asia (excluding Japan), and Oceania.
Subjects of the SCARLET study were patients with sepsis-associated cardiovascular dysfunction or respiratory dysfunction, and coagulopathy (PT-INR* > 1.4 and platelet count greater than 30,000/mm3 but less than 150,000/mm3 or decreasing by over 30% within 24 hours). The intended indication of the development, severe sepsis with coagulopathy, differs from the approved indication for ART-123 in Japan, disseminated intravascular coagulation (DIC).
A statistically significant difference was not observed in 28-day all-cause mortality, the primary endpoint of the SCARLET study. Whereas 28-day all-cause mortality for the group given ART-123 was 26.8% (106 of 395 cases), that for the control group was 29.4% (119 of 405 cases), the difference being 2.6%. The reason a statistically significant difference was not observed may be that there were some patients whose coagulopathy improved before administration, and some patients who received half or fewer of the planned six doses of study drug.
Initially planned analysis (item 1, below) and ad-hoc analysis (item 2, below) have thus far indicated the following results.
- 1．As in the Phase II-b study, improvements were observed in the level of each of the blood coagulation markers D-dimer, thrombin-antithrombin complex, and prothrombin fragment F1+2, as well as in platelet count.
- 2．Among patients for whom both PT-INR and platelet count criteria were met just before study drug administration (approximately 600 cases), the difference in 28-day all-cause mortality between the group given ART-123 and the control group was at least 4.5%. Limiting this segment of patients to those who received at least four doses (approximately 450 cases), the difference in 28-day all-cause mortality between the group given ART-123 and the control group was approximately 7%.
Asahi Kasei Pharma is currently performing further analyses. Judgement concerning the potential for ART-123 as a useful treatment of severe sepsis with coagulopathy will be made through careful consideration of forthcoming analytical results.
With regard to safety, no new concerns have been identified at this stage.
Asahi Kasei Pharma will also perform further analysis not only of 28-day all-cause mortality for which results were obtained, but also of 90-day all-cause mortality, etc., while consulting with the relevant regulatory authorities. Details will be reported at scientific conferences, etc.