Moderately Severe To Severe Adult Hemophilia B Subjects (FIX:C=2%) Who Are Negative For Neutralizing Antibodies (NAb) To Adeno-Associated Virus Vector (AAV)-Spark100. MedDRA version: 20.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Name: Not Applicable
Product Code: Not Applicable
Pharmaceutical Form: Powder and solvent for solution for injection/infusion
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.Males 18 and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Anti-AAV-Spark100 neutralizing antibodies titer (above the lowest detectable titer) performed by a central laboratory during screening. 2. Lack of patient compliance with documentation of bleeds and/or FIX prophylaxis replacement therapy administration. 3. If there is no documentation regarding hepatitis status, as defined below, within the last 12 months prior to screening for hepatitis B and 6 months prior to screening for hepatitis C, then subjects will be required to have the following hepatitis testing performed at screening: a. Hepatitis B screening (acute and chronic): HBsAg (also referred to as Hepatitis B surface antigen), HBV-DNA viral assay (also referred to as a nucleic acid test for Hepatitis B virus DNA), and Anti-HBc (also referred to as Total Hepatitis B core antibody). -A subject is not eligible if either HbsAg is positive or HBV-DNA is positive/detectable. -Anti-HBc must be obtained in all subjects for determination of whether the subject had prior hepatitis B. If the anti-HBc is positive and both HBsAg and HBV DNA are negative this would be consistent with a prior infection and the subject would be eligible for the study. Anti-HBc must be obtained in all subjects to discriminate between those with no prior hepatitis B and those with prior infection in the event of reactivation. FDA has noted reactivation of hepatitis B virus exists. -One documented negative HBV-DNA viral load is sufficient to assess eligibility. A subject who is currently undergoing anti-viral therapy for hepatitis B is not eligible. b. Hepatitis C (acute or chronic): -A subject who is currently undergoing anti-viral therapy for chronic hepatitis C is not eligible. -Subjects treated with anti-viral therapy for chronic hepatitis C, must have completed anti-viral therapy at least 6 months prior to screening and have a negative HCV-RNA at least 6 months prior to screening. -All subjects (who are not currently undergoing anti-viral therapy for chronic hepatitis C) must have a single HCV-RNA load assay (also referred to as a nucleic acid test [NAT] for HCV RNA) obtained during the 6 months preceding screening. This includes subjects with prior known chronic hepatitis C who have completed treatment with anti-viral therapy. -A subject is not eligible if his HCV-RNA load assay result is positive/detectable. 4. Currently on antiviral therapy for hepatitis B or C. 5. A subject is not eligible if any of the following pre-existing diagnoses, which are indicative of significant underlying liver disease, are present in the medical record: - Portal hypertension; or - Splenomegaly; or - Hepatic encephalopathy. All subjects who do not have the listed pre-existing diagnoses above must have the following assessments performed within the last 12 months prior to screening and if not will need to be tested for liver fibrosis status at screening: -Measurement of serum albumin. A subject is not eligible if the serum albumin level is below the testing laboratory’s lower limit of normal; and -At least one of the following diagnostic tests for liver fibrosis indicating = stage 3. The following results are indicative of fibrosis = stage 3 and exclude the subject from participation: -FibroScan, with a score >8.3 kPa units; -FibroTest/FibroSURE with a result >0.48; or -AST-to-Platelet Ratio Index (APRI) >1. 6. Documented serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with Cluster of Differentiation 4 positive (CD4+) cell count =200 m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish a minimum of 6 months of prospective efficacy data of FIX prophylaxis replacement therapy in the usual care setting of hemophilia B subjects, who are negative for NAb to AAV-Spark100. ;Secondary Objective: Evaluate safety (serious adverse events and medically important events of FIX inhibitor, thrombotic and FIX hypersensitivity reactions) of FIX replacement therapy in hemophilia B subjects. ;Primary end point(s): Efficacy Endpoints: 1)Annualized bleeding rate (ABR). Safety Endpoints: 1)Incidence of serious adverse events. 2)Events of Special Interest: -FIX inhibitor; -Thrombotic events; -FIX hypersensitivity events. ;Timepoint(s) of evaluation of this end point: Efficacy analysis population is defined as subjects identified as NAb negative during screening and have completed a minimum of 6 months data collection. Safety Endpoints: From Screening visit: Day - 42 to Day -1 till End of Study / Early Termination Visit: Minimum 180 days from Day 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoints: 1)Annualized number of infusions (AIR);Timepoint(s) of evaluation of this end point: Efficacy analysis population is defined as subjects identified as NAb negative during screening and have completed a minimum of 6 months data collection. | — |
Countries
Australia, Brazil, Canada, European Union, France, Germany, Ireland, Israel, Japan, Korea, Democratic People's Republic of, Netherlands, Saudi Arabia, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Center
Pfizer Inc.
Outcome results
None listed