Health Condition 1: D66- Hereditary factor VIII deficiency
Conditions
Interventions
Intervention1: Fitusiran: Fitusiran solution for injection in Phosphate buffered saline (Subcutaneous use) supplied as
a sterile solution.
Dosages administered as per the weight of the participants
Sponsors
Sanofi Healthcare India Private Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male, must be 1 to less than 12 years of age at the time of enrollment. 2. Severe hemophilia A or B (FVIII less than1percent or FIX less than equal to 2percent) as evidenced by a central laboratory measurement at screening or documented medical record evidence. 3. Must meet inhibitor or non-inhibitor status as defined below- Inhibitor- 4. Use of BPA for prophylaxis or as on-demand therapy for any bleeding episodes for at least the last 3 months prior to screening, and meet one of the following Nijmegen-modified Bethesda assay results criteria: 4aa Inhibitor titer of more than equal to 0.6 Bethesda units (BU)/mL at Screening, OR 4bb Inhibitor titer of less than 0.6 BU/mL at Screening with medical record evidence of 2 consecutive titers more than equal to 0.6 BU/mL, OR 4cc Inhibitor titer of less than 0.6 BU/mL at Screening with medical record evidence of 1 inhibitor titer more than equal to 0.6 BU/mL and a history of anamnestic response, or severe allergic reaction (eg, anaphylaxis) or nephrotic syndrome Non-inhibitor: 5Use of CFC for prophylaxis or as on-demand therapy for any bleeding episodes, and meet each of the following criterion: 5aa Nijmegen-modified Bethesda assay inhibitor titer of less than 0.6 BU/mL at Screening, AND 5bb No use of BPA to treat bleeding episodes for at least the last 3 months prior to Screening
Exclusion criteria
Exclusion criteria: 1. Known co-existing bleeding disorders other than hemophilia A or B, ie, Von Willebrands disease, additional factor deficiencies, or platelet disorders. 2. AT activity less than 60percent at Screening, as determined by central laboratory measurement. 3. Presence of clinically significant liver disease, or as indicated by any of the conditions below: 4. International normalized ratio (INR) more than 1.2; 5. ALT and/or AST more than 2 Ã? ULN reference range; 6. Total bilirubin more than ULN (more than 2 Ã? ULN in participants with Gilberts syndrome); 7. History of portal hypertension, esophageal varices, or hepatic encephalopathy; 8. Presence of ascites by physical examination 9. Hepatitis C virus antibody positive, except subjects with a history of HCV infection who meet both of the following conditions: 10. Completed curative treatment at least 12 weeks prior to enrollment and attained sustained virologic response as documented by a negative HCV ribonucleic acid (RNA) at screening, or they have spontaneously cleared the infection as documented by negative HCV RNA at screening. 11. No evidence of cirrhosis according to either a Fibroscan (less than 9 Kpa) OR FibroTest score less than 0.36 and AST to platelet ratio index (APRI) less than 1 (if FibroScan was not available) 12. Presence of acute hepatitis, ie, hepatitis A, hepatitis E. 13. Presence of acute or chronic hepatitis B infection (IgM anti-HBc antibody positive or HBsAg positive). 14. Co-existing thrombophilic disorder, as determined by presence of any of the below as identified at central laboratory: 15. FV Leiden mutation (homozygous or heterozygous) 16. Protein S deficiency 17. Protein C deficiency 18. Prothrombin mutation (G20210A; homozygous and heterozygous) 19. Platelet count less than equal to 100,000/uL. 20. Presence of acute infection at Screening. 21. Known to be HIV positive with CD4 count less than 400 cells/uL. 22. eGFR more than equal to 45 mL/min/1.73m2 (using the Schwartz formula). 23. History of antiphospholipid antibody syndrome. 24. History of arterial or venous thromboembolism, unrelated to an indwelling venous access 25. Any condition which, in the opinion of the Investigator, would make the participant unsuitable for dosing on Day 1 or which could interfere with the study compliance, the participants safety and/or the participants participation in the completion of the treatment period of the study. 26. Anticipated or planned surgery scheduled to occur during the study. 27. Subjects with a central or peripheral indwelling catheter, with a history of venous access complications (such as infections, thrombosis) leading to hospitalization and/or systemic anticoagulation therapy in the last 12 months. 28. Current participation in immune tolerance induction therapy (ITI). 29. The use of emicizumab (Hemlibra) or any non-factor bleed management treatment within 6 months prior to screening. 30. Prior gene therapy 31. History of intolerance to SC injection(s)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate treatment efficacy during fitusiran prophylaxis and standard of care (SOC) periods in the fitusiran-naïve armTimepoint: Annualized treated bleeding rate (ABR) in the fitusiran primary efficacy period (Day 85 to Day 421) and in the SOC period (Week -24 to Day -1) | — |
Secondary
| Measure | Time frame |
|---|---|
| To characterize the following during the fitusiran prophylaxis & SOC periods in the fitusiran-naive arm: The frequency of treated spontaneous bleeding episodes The frequency of treated joint bleeding episodesTimepoint: Annualized spontaneous bleeding rate (AsBR) in the fitusiran primary efficacy period (Day 85 to Day 421) & in the SOC period (Week -24 to Day -1) Annualized joint bleeding rate (AjBR) in the fitusiran primary efficacy period (Day 85 to Day 421) & in the SOC period (Week -24 to Day -1);To characterize the frequency of treated bleeding episodes during the fitusiran treatment period in both armsTimepoint: ABR in the fitusiran treatment period (160 weeks) for fitusirannaive participants ABR in the fitusiran treatment period (60 weeks) for rolled-over participants;To characterize the effect of fitusiran prophylaxis on health-related quality of life (HRQoL) outcomes in the fitusirannaive armTimepoint: Change in physical activity, as measured via the PROMIS Parent Proxy Short Form v1.0 Physical Activity 4a (more than 5 yearsold): From Day 1 to Day 421,From Week -24 to Day -1 Change in pain intensity, as measured via the PROMIS Numeric Rating Scale v1.0 â?? Parent Proxy Pain Intensity 1a (more than equal to 5 years old):From Day 1 to Day 421,From Week -24 to Day -1,Change in HRQoL, as measured by the EQ-5D-Y-3L Proxy version 1 (more than 4 years old): From Day 1 to Day 421,From Week -24 to Day -1;To characterize the safety of fitusiran in both armsTimepoint: Incidence, severity, seriousness, and relatedness of adverse events (AEs);To characterize the effect of fitusiran prophylaxis on joint health outcomes in the fitusiran-naïve arm.Timepoint: Change in total score & domain scores as assessed by the Hemophilia Joint Health Score From Day 1 to Day 421 From Week -24 to Day -1 Target joints resolution at Day 421 per ISTH criteria | — |
Countries
Belgium, Brazil, Canada, China, Germany, Hungary, India, Italy, Poland, Romania, Saudi Arabia, Spain, Taiwan, Turkey, United States of America
Contacts
Public ContactDhara Patel
Sanofi Healthcare India Private Limited
Outcome results
None listed