a study of fitusiran (aln-at3sc) in severe hemophilia a and b patients without inhibitors

Conditions: Hemophilia A; Hemophilia B

Summary: primary objective: -to evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by the frequency of bleeding episodes. secondary objectives: * to evaluate the efficacy of fitusiran compared to on-demand treatment with factor concentrates, as determined by: * the frequency of spontaneous bleeding episodes. * the frequency of joint bleeding episodes. * health-related quality of life (hrqol) in participants \>=17 years of age. * to determine the frequency of bleeding episodes during the onset period. * to determine the safety and tolerability of fitusiran.

the duration of treatment with fitusiran was 9 months. the estimated total time on study, inclusive of screening, was up to 11 months for all participants in the factor on-demand arm and for participants in the fitusiran arm who enrolled in the extension study (lte15174). the estimated total time on the study was up to 17 months for participants in the fitusiran treatment arm who did not enroll in the extension study due to the requirement for up to an additional 6 months of follow-up monitoring for antithrombin levels. participants who completed the study will be eligible for an open-label extension study lte15174 (nct03754790).

Eligibility criteria:
inclusion criteria: * males, \>=12 years of age. * severe hemophilia a or b without inhibitors. * severity confirmed by a central laboratory where fviii level was less than (\<) 1 percent (%) or factor ix (fix) level was less than or equal to (\<=) 2% at screening. * on-demand use of factor concentrate to manage bleeding episodes for at least the last 6 months prior to screening, and meet each of the following criterion: * nijmegen modified bethesda assay inhibitor titer of \<0.6 bethesda units per milliliter (bu/ml) at screening. * no use of bypassing agents to treat bleeding episodes for at least the last 6 months prior to screening. * no history of immune tolerance induction therapy within the last 3 years prior to screening. * a minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to screening. * willing and complied with the study requirements and to provide written informed consent and assent. exclusion criteria: * known co-existing bleeding disorders other than hemophilia a or b, i.e., von willebrand's disease, additional factor deficiencies, or platelet disorders. * antithrombin (at) activity \<60% at screening. * co-existing thrombophilic disorder. * clinically significant liver disease. * active hepatitis c virus infection. * hiv positive with a cluster of differentiation-4 count of \<200 cells/microliter. * history of arterial or venous thromboembolism. * inadequate renal function. * history of multiple drug allergies or history of allergic reaction to an oligonucleotide or n-acetylgalactosamine (galnac). * history of intolerance to sc injection(s). * any other conditions or comorbidities that would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per investigator judgment.

Keywords: rnai therapeutic hemophilia a hemophilia b hemophilia a, severe hemophilia b, severe blood coagulation disorders, inherited blood coagulation disorders hematologic diseases coagulation protein disorders hemorrhagic disorders genetic diseases, inborn genetic diseases, x-linked factor viii factor ix coagulants fitusiran