A Study of Fitusiran (ALN-AT3SC) in Severe Hemophilia A and B Patients Without Inhibitors
Condition: Hemophilia A; Hemophilia B
MeSH terms: Hemophilia A; Hemophilia B
Intervention: fitusiran; factor concentrates
Intervention description: by SC injection; by intravenous (IV) injection
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 120.0
Sex: Male
Minimum age: 12 Years
Healthy volunteers: No
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

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.
    

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.