A Phase 3 Study to Evaluate the Efficacy and Safety of Fitusiran in Patients with Hemophilia A or B, without Inhibitory Antibodies to Factor VIII or IX
- Conditions
- Health Condition 1: null- Hemophilia AHemophilia B
- Registration Number
- CTRI/2018/07/014698
- Lead Sponsor
- Sanofi Genzyme
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Closed to Recruitment of Participants
- Sex
- Not specified
- Target Recruitment
- 0
1) Males, >=12 years of age
2) Severe hemophilia A or B without inhibitors evidenced by:
a. A central laboratory measurement or documented medical record evidence of
FVIII <1% or FIX level <=2% at Screening.
b. On-demand use of factor concentrate to manage bleeding episodes for at least the last
6 months prior to Screening
3) A minimum of 6 bleeding episodes requiring factor concentrate treatment within the last 6 months prior to Screening.
4) Willing and able to comply with the study requirements and to provide written informed consent and assent in the case of patients under the age of legal consent, per local and
national requirements.
1. Known co-existing bleeding disorders other than hemophilia A or B, ie, Von
Willebrandâ??s disease, additional factor deficiencies, or platelet disorders.
2. Current use of factor concentrates as regularly administered prophylaxis designed to
prevent spontaneous bleeding episodes.
3. AT activity <60% at Screening as determined by central laboratory measurement.
4. Presence of clinically significant liver disease, or as indicated by any of the conditions
below:
a. INR >1.2;
b. ALT and/or AST >1.5Ã? upper limit of normal reference range (ULN);
c. Total bilirubin >ULN ( >1.5 ULN in patients with Gilbertâ??s Syndrome);
d. History of portal hypertension, esophageal varices, or hepatic encephalopathy;
e. Presence of ascites by physical exam
5. Hepatitis C virus antibody positive, except patients with a history of HCV infection who
meet both conditions a. and b.:
a. Completed curative treatment at least 12 weeks prior to enrollment and attained
sustained virologic response as documented by a negative HCV RNA at screening, or
they have spontaneously cleared infection as documented by negative HCV RNA at
Screening.
b. No evidence of cirrhosis
6. Presence of acute hepatitis, ie, hepatitis A, hepatitis E.
7. Presence of acute or chronic hepatitis B infection (IgM anti-HBc antibody positive or
HBsAg positive).
8. Platelet count <=100,000/μL.
9. Presence of acute infection at Screening.
10. Known to be HIV positive with CD4 count <200 cells/μL.
11. Estimated glomerular filtration rate <=45 mL/min/1.73m2 (using the Modification of Diet
in Renal Disease [MDRD] formula).
12. Co-existing thrombophilic disorder, as determined by presence of any of the below as
identified at central laboratory (or via historical results, where available):
a. FV Leiden (homozygous or heterozygous)
b. Protein S deficiency
c. Protein C deficiency
d. Prothrombin mutation (G20210A; homozygous or heterozygous)
13. History of antiphospholipid antibody syndrome.
14. History of arterial or venous thromboembolism, atrial fibrillation, significant valvular
disease, myocardial infarction, angina, transient ischemic attack, or stroke. Patients who
have experienced thrombosis associated with indwelling venous access may be enrolled.
15. Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin
that has been successfully treated.
16. Any condition (eg, medical concern), which in the opinion of the Investigator, would
make the patient unsuitable for dosing on Day 1 or which could interfere with the study
compliance, the patientâ??s safety and/or the patientâ??s participation in the completion of the
treatment period of the study. This includes significant active and poorly controlled
(unstable) cardiovascular, neurologic, gastrointestinal, endocrine, renal or psychiatric
disorders unrelated to hemophilia identified by key laboratory abnormalities or medical
history.
17. At Screening, anticipated need of surgery during the study or planned surgery scheduled
to occur during the study.
18. Completion of a surgical procedure within 14 days prior to Screening, or currently
receiving additional factor infusion for p
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Annualized bleeding rate (ABR)Timepoint: Annualized bleeding rate (ABR) : 9 months
- Secondary Outcome Measures
Name Time Method 1. Annualized spontaneous bleeding rate <br/ ><br> <br/ ><br>2. Annualized joint bleeding rate <br/ ><br> <br/ ><br>3. Quality of Life (QOL) as measured by Haem-A-QOL Questionnaire score on a scale of 0-100 with higher scores representing greater impairment <br/ ><br>Timepoint: 9 months <br/ ><br>9 months <br/ ><br>9 months