Clinical trial: Six Month lead-in Study to Evaluate Prospective Efficacy and Safety Data of Current FIX Prophylaxis Replacement Therapy in Adult Hemophilia B Subjects (FIX:C≤2%) or Current FVIII Prophylaxis Replacement Therapy in Adult Hemophilia A Subjects (FVIII:C≤1%) (NCT03587116)

Eligibility criteria:
Inclusion Criteria:

        Hemophilia B Population:

          1. Evidence of a personally signed and dated informed consent document indicating that
             the subject 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 <65 years of age with moderately severe to severe hemophilia B and
             documented FIX activity (≤2%) prior to baseline visit.

          4. Previous experience with FIX therapy (≥50 documented exposure days to a FIX protein
             product such as recombinant, plasma-derived or extended half-life FIX product).

          5. Subjects 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. Subjects will not be required to undergo diagnostic
                  evaluation of inhibitor status to participate in the study.

        Hemophilia A Population:

          1. Evidence of a personally signed and dated informed consent document indicating that
             the subject 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 <65 years of age with moderately severe to severe hemophilia A and
             documented FVIII activity (≤1%) prior to baseline visit.

          4. Previous experience with FVIII therapy (≥150 documented exposure days to a FVIII
             protein product such as recombinant, plasma-derived or extended half-life FVIII
             product).

          5. Subjects 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. Subjects will not be required to undergo diagnostic evaluation of
             inhibitor status to participate in the study.

        Exclusion Criteria:

          1. Anti-AAV-Spark100 neutralizing antibody titer above or equal to 1:1 performed by a
             central laboratory during screening in hemophilia B subjects or Anti- SB-525 capsid
             (AAV6) neutralizing antibody titer (above or equal to the lowest detectable titer)
             performed by a central laboratory during screening in hemophilia A subjects.

          2. Lack of patient 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 subjects will be required to have the following hepatitis testing
             performed at screening:

               1. 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.

               2. 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

               -  One of the following diagnostic tests for liver fibrosis. The following results
                  are indicative of fibrosis 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.

                    -  Please note, if a subject has a known history of Gilbert's syndrome, a
                       FibroTest cannot be used for fibrosis testing.

          6. Documented serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with
             Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 within the last 12
             months prior to screening. Subjects who are HIV positive and stable, have an adequate
             CD4 count (>200/mm3) and undetectable viral load (<50 gc/mL) documented within the
             preceding 12 months, and are on an antiretroviral drug regimen are eligible to enroll.
             Subjects who have not been tested within the prior 12 months of screening will need to
             be tested for HIV status at screening.

          7. History of chronic infection or other chronic disease that the investigator deems an
             unacceptable risk. Any patient with a history of thrombotic events including but not
             limited to stroke or myocardial infarction.

          8. Any concurrent clinically significant major disease or condition that the investigator
             deems unsuitable for participation or other acute or chronic medical or psychiatric
             condition including recent (within the past year) or active suicidal ideation or
             behavior or laboratory abnormality that may increase the risk associated with study
             participation or may interfere with the interpretation of study results and, in the
             judgment of the investigator, would make the subject inappropriate for entry into this
             study.

          9. Participation in other studies involving investigational drug(s) within the last 3
             months prior to study entry and/or during study participation or in a previous gene
             therapy clinical study within the last 12 months prior to screening.

         10. Any subject who previously received fidanacogene elaparvovec (SPK-9001) (hemophilia B)
             or SB-525 (hemophilia A) or any AAV gene-based therapy.

         11. Any subject with a planned surgical procedure requiring FIX (hemophilia B) or FVIII
             (hemophilia A) surgical prophylactic factor treatment in the next 24 months.

         12. Investigator site staff members directly involved in the conduct of the study and
             their family members, site staff members otherwise supervised by the investigator, or
             subjects who are Pfizer employees, including their family members, directly involved
             in the conduct of the study.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 64 Years

Patient description (medical language): A 20-year-old man comes to the emergency due to bleeding after a tooth extraction.  The bleeding has persisted for approximately 30 minutes despite constant direct pressure.  He is a known case of Hemophilia type A treated with FVIII. Blood pressure is 95/60 mm Hg and pulse is 105/min. His weight is 70 Kg. Family history is positive for Hemophilia type A in his maternal uncle. He also has a lipoma on his left arm which he plans to remove surgically. His FVIII activity is 40%.

Patient description (patient's own words): I got my tooth extracted and I could not stop bleeding for 30 min. I'm a 20 yo dude but I have Hemophilia type A treated with FVIII. My blood pressure was 95/60 and my pulse 105/min. I'm 70 kg. My uncle on my mom's side also has type A hemophilia. I also have a fatty swelling on my left arm and I was supposed to remove it. My FVIII activity was 40%.

Does the patient match the trial criteria? 0