Hemophilia A or Hemophilia B MedDRA version: 20.0 Level: LLT Classification code 10060613 Term: Hemophilia A (Factor VIII) System Organ Class: 100000004850 MedDRA version: 20.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: ALN-AT3SC
Product Code: ALN-AT3SC
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ALN-57213
CAS Number: 1
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Completed and tolerated study drug dosing in study ALN-AT3SC-001. Male aged =18 years. Moderate or severe, clinically stable hemophilia A or B as evidenced by a laboratory FVIII or FIX level =5% at screening. Patients with a FVIII or FIX level >5% at screening will be eligible on provision of a historic laboratory report indicating a trough level =5%. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: Liver disease defined as clinically significant cirrhosis as determined by the Investigator, INR >1.5 at Screening, ALT/AST >3× upper limit of the normal reference range (ULN), platelet count =120,000/mL and/or other complete blood count test results that are considered clinically significant and unacceptable by the Investigator, or known hepatitis C virus currently requiring treatment with ribavirin or interferon. Patients known to be human immunodeficiency virus seropositive and have a CD4 count <200 cells/µL at screening. History of venous thromboembolism. Current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity. Uncontrolled hypertension. Clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory, or other diseases that, in the judgment of the Investigator, precludes study participation. If using nonsteroidal anti-inflammatory drugs intermittently or chronically, must tolerate them with no previous side effects.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of ALN AT3SC in male patients with moderate or severe hemophilia A or B.;Secondary Objective: To investigate the long-term efficacy of ALN-AT3SC, characterize the safety and efficacy of concomitantly administered factor VIII (FVIII) or factor IX (FIX) and ALN-AT3SC for treatment of bleeding episodes, antithrombin (AT) reduction and thrombin generation (TG) increase, the pharmacokinetics (PK) of ALN AT3SC, and assess changes in health-related quality of life (QOL) over time.;Primary end point(s): Safety assessments will include monitoring for AEs (including serious AEs [SAEs]), clinical laboratory evaluations (including hematology, biochemistry, urinalysis, and coagulation), vital signs, 12-lead electrocardiogram (ECG), antidrug antibodies, and physical examinations.;Timepoint(s) of evaluation of this end point: Through 27 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The PK of ALN-AT3SC, evaluated by: •plasma PK profiles of ALN-AT3C determined at specified time points •Urine collected (spot collection and pooled) to determine the amount PD effect of ALN-AT3SC, evaluated by the following biomarkers: •Plasma AT levels (activity and antigen-based). •Plasma TG as determined by the calibrated automated thrombogram (CAT) assay. ;Timepoint(s) of evaluation of this end point: Through 27 months | — |
Countries
Bulgaria, Russian Federation, Switzerland, United Kingdom, United States
Outcome results
None listed