a study of fitusiran in severe hemophilia a and b patients previously receiving factor or bypassing agent prophylaxis

Conditions: Hemophilia

Summary: primary objective: to characterize the frequency of bleeding episodes (be) while receiving fitusiran treatment, relative to the frequency of bleeding episodes while receiving factor concentrate or bypassing agent (bpa) prophylaxis. secondary objectives: * to characterize the following while receiving fitusiran treatment, relative to receiving factor or bpa prophylaxis: * the frequency of spontaneous bleeding episodes * the frequency of joint bleeding episodes * health related quality of life (hrqol) in participants greater than or equal to (\>=) 17 years of age * to characterize the frequency of bleeding episodes during the onset and treatment periods in participants receiving fitusiran. * to characterize the safety and tolerability of fitusiran. * to characterize the annualized weight-adjusted consumption of factor/bpa while receiving fitusiran treatment, relative to receiving factor or bpa prophylaxis.

the estimated total time on study, inclusive of screening, for each participant was up to 15 months for participants who were enrolled in the extension study except for participants in the subgroup of cohort a, for whom it was up to 9 months. the estimated total time on study was up to 21 months (up to 15 months in participants in the subgroup of cohort a) in participants who did not enroll in the extension study due to the requirement for an additional up to 6 months of follow-up for monitoring of antithrombin (at) levels.

Eligibility criteria:
inclusion criteria: * males, \>=12 years of age. * severe hemophilia a or b (as evidenced by a central laboratory measurement at screening or documented medical record evidence of fviii less than (\<) 1 percent (%) or fix level less than or equal to (\<=) 2%). * a minimum of 2 bleeding episodes required bpa treatment within the last 6 months prior to screening for participants with inhibitory antibodies to factor viii or factor ix (cohort a). a minimum of 1 bleeding episode required factor treatment within the last 12 months prior to screening for participants without inhibitory antibodies to factor viii or factor ix (cohort b). * met either the definition of inhibitor or non-inhibitor participant as below: * inhibitor: use of bpas for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met one of the following nijmegen-modified bethesda assay results criteria: * inhibitor titer of \>=0.6 bethesda unit per milliliter (bu/ml) at screening, or * inhibitor titer of \ =0.6 bu/ml, or * inhibitor titer of \<0.6 bu/ml at screening with medical record evidence of anamnestic response * the subgroup of participants in cohort a participants might additionally meet the following criteria to be eligible to start treatment with fitusiran directly after the screening period: * hemophilia b with inhibitory antibody to factor ix as defined above * not responding adequately to bpa treatment (historical abr \>=20) prior to enrollment * in the opinion of the investigator, with approval of sponsor medical monitor, 6-month bpa prophylaxis period should be omitted. * non-inhibitor: use of factor concentrates for prophylaxis and for any bleeding episodes for at least the last 6 months prior to screening, and met each of the following criterion: * nijmegen-modified bethesda assay inhibitor titer of \<0.6 bu/ml at screening and * no use of bpas to treat bleeding episodes for at least the last 6 months prior to screening and * no history of immune tolerance induction therapy within the past 3 years prior to screening. * documented prophylactic treatment with factor concentrates or bpas for the treatment of hemophilia a or b for at least 6 months prior to screening. * adherent to the prescribed prophylactic therapy for at least 6 months prior to screening per investigator assessment. * willed 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. * at activity \<60% at screening. * co-existing thrombophilic disorder. * clinically significant liver disease. * active hepatitis c virus infection. * acute or chronic hepatitis b virus infection. * hiv positive with a cd4 count of \<200 cells per 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 subcutaneous injection(s). * any other conditions or comorbidities that made the participant unsuitable for enrollment or could interfere with participation in or completion of the study, per investigator judgment.