Hemophilia A or Hemophilia B
Conditions
Interventions
investigational material(s)
Generic name etc : -
INN of investigational material :
Therapeutic category code :
Dosage and Administration for Investigational material : -
control material(s)
Generic
Sponsors
Pfizer R&D Japan G.K.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Inclusion Criteria: Hemophilia B Population: 1.Evidence of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study. 2.Willing and able to comply with scheduled visits, FIX prophylaxis treatment plan, laboratory tests and other study procedures. 3.Males >= 18 and =50 documented exposure days to a FIX protein product such as recombinant, plasma-derived or extended half-life FIX product). 5.Participants on FIX prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FIX product) must have the intention to remain on FIX prophylaxis replacement therapy for the duration of the study. 6.No known hypersensitivity to FIX replacement product. 7.No history of FIX inhibitor (clinical or laboratory-based assessment) defined as a titer * 0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FIX administration. Participants will not be required to undergo diagnostic evaluation of inhibitor status to participate in the study. Hemophilia A Population: 1.Evidence of a signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study. 2.Willing and able to comply with scheduled visits, FVIII prophylaxis treatment plan, laboratory tests and other study procedures. 3.Males >=18 and =150 documented exposure days to a FVIII protein product such as recombinant, plasma-derived or extended half-life FVIII product). 5.Participants on FVIII prophylaxis replacement therapy (recombinant, plasma-derived or extended half-life FVIII product) must have the intention to remain on FVIII prophylaxis replacement therapy for the duration of the study. 6.No known hypersensitivity to FVIII replacement product. 7.No history of FVIII inhibitor (clinical or laboratory-based assessment) defined as a titer >=0.6 BU/mL, regardless of the laboratory normal range, or any measured Bethesda inhibitor titer greater than the upper limit of normal for the laboratory performing the assay. Clinically, no signs or symptoms of decreased response to FVIII administration. Participants will not be required to undergo diagnostic evaluation of inhibitor status to participate in the study.
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1.Anti-AAV-Spark100 neutralizing antibody titer above the established threshold performed by a central laboratory during screening in hemophilia B subjects or Anti-AAV6 neutralizing antibody titer above the established threshold performed by a central laboratory during screening in hemophilia A subjects. 2.Lack of participant compliance with documentation of bleeds and/or 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 participants 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 participant is not eligible if either HbsAg is positive or HBV-DNA is positive/detectable. * Anti-HBc must be obtained in all participants for determination of whether the participant 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 participant who is currently undergoing anti-viral therapy for hepatitis B is not eligible. b.Hepatitis C (acute or chronic): * A participant who is currently undergoing anti-viral therapy for chronic hepatitis C is not eligible. * Participants 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 participants (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 participants with prior known chronic hepatitis C who have completed treatment with anti-viral therapy. * A participant is not eligible if his HCV-RNA load assay result is positive/detectable. 4.Currently on antiviral therapy for hepatitis B or C. 5.Significant liver disease, as defined by pre-existing diagnosis of portal hypertension, splenomegaly, or hepatic encephalopathy. All participants 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: a serum albumin level below normal limits and/or significant liver fibrosis by any of the following diagnostic modalities: FibroScan score >8 kPa units OR FibroTest/FibroSURE >0.48*. * NOTE: If there is concern regarding the validity of any of the liver fibrosis test results please contact the medical monitor to discuss whether any additional testing needs to be performed (ie, either repeating any test or performing another fibrosis test). Also, note, if a participant has a known history of Gilbert's syn
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Annualized bleeding rate (ABR) [ Time Frame: 6 months ] The annualized bleeding rate (ABR) per subject will be calculated as the number of bleeds over number of days subject received FIX prophylaxis replacement therapy from baseline visit (Day 1) to end of study x 365.25 days. ABR will be summarized using descriptive statistics (n, mean, standard deviation, median, Q1, Q3, minimum, maximum). The annualized bleeding rate (ABR) per subject will be calculated as the number of bleeds over number of days subject received FVIII prophylaxis replacement therapy from baseline visit (Day 1) to end of study x 365.25 days. ABR will be summarized using descriptive statistics (n, mean, standard deviation, median, Q1, Q3, minimum, maximum). Incidence of serious adverse events [ Time Frame: 6 months ] The primary safety analysis will be performed on all subjects that sign the informed consent document and are subsequently identified as nAb negative and are enrolled (complete baseline visit) into the study. Events of special interest (ESI):inhibitor against FIX or FVIII, thrombotic events, and FIX or FVIII hypersensitivity reactions [ Time Frame: 6 months ] Frequency and percentage of these ESI events will be summarized by event. In addition any events leading to discontinuation from the study will be described. | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy Annualized infusion rate (AIR) [ Time Frame: 6 months ] The annualized infusion rate (AIR) per subject will be calculated as the number of infusions received over number of days subject received FIX prophylaxis replacement therapy from baseline visit (Day 1) to end of study x 365.25 days. AIR will be summarized using descriptive statistics (n, mean, standard deviation, median, Q1, Q3, minimum, maximum). The annualized infusion rate (AIR) per subject will be calculated as the number of infusions received over number of days subject received FVIII prophylaxis replacement therapy from baseline visit (Day 1) to end of study x 365.25 days. AIR will be summarized using descriptive statistics (n, mean, standard deviation, median, Q1, Q3, minimum, maximum). Dose and total factor consumption [ Time Frame: 6 months ] The total factor IX replacement therapy consumption and the corresponding dose will be descriptively summarized by the categories of the replacement therapy, where appropriate. Infusion diary (electronic infusion diary) of the factor IX replacement therapy will be listed. The total factor VIII replacement therapy consumption and the corresponding dose will be descriptively summarized by the categories of the replacement therapy, where appropriate. Infusion diary (electronic infusion diary) of the factor VIII replacement therapy will be listed. Number of bleeding events (spontaneous and/or traumatic) [ Time Frame: 6 months ] The number of bleeding episodes will be summed up by spontaneous, traumatic and overall as defined as any bleed occurring >72 hours after stopping treatment from the original bleed for which treatment was initiated or a bleed occurring at a different site from the original bleed regardless of the time from last injection. | — |
Countries
Australia, Belgium, Brazil, Canada, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Saudi Arabia, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Information Desk
Pfizer R&D Japan G.K.
Outcome results
None listed