Clinical trial: A Study of BAX 888 in Male Adults With Severe Hemophilia A (NCT03370172)

Eligibility criteria:
Inclusion Criteria:

          -  Male, aged 18 to 75 years at the time of screening.

          -  Established severe hemophilia A (FVIII:C <1%, measured following >=5 days without
             FVIII treatment) and/or documented intron 1 inversion or intron 22 inversion mutation
             in the F8 gene, consistent with severe hemophilia A , and documented evidence of >=3
             hemorrhages over the previous 12 months requiring treatment with exogenous FVIII or
             use of FVIII prophylaxis because of history of frequent bleeding episodes.

          -  History of greater than (>) 150 exposure days to exogenously administered FVIII
             concentrates or cryoprecipitate.

          -  Sexually active men must agree to use barrier contraception (combination of a condom
             and spermicide) or limit sexual intercourse to post-menopausal, surgically sterilized,
             or contraception-practicing partners for a minimum of 6 months after administration of
             BAX 888, or until BAX 888 genomes are no longer detected in the semen, whichever is
             sooner.

          -  Participant is willing and able to comply with the requirements of the protocol,
             including provision of semen samples, maintenance of a diary of bleeding episodes and
             FVIII protein use.

          -  Signed informed consent.

        Exclusion Criteria:

          -  Bleeding disorder(s) other than hemophilia A.

          -  Personal laboratory evidence of having developed inhibitors to FVIII protein at any
             time (>=0.6 Bethesda units [BU] on any single test).

          -  Documented prior allergic reaction to any FVIII product.

          -  Anti-Adeno-associated virus, serotype 8 (AAV8) neutralizing antibody titer >=1:5.
             Participants whose laboratory assessments are less than or equal to (<=) 1:10 may be
             re-tested within the same screening window and, if eligibility criterion is met on
             retest, may be enrolled after confirmation by the Sponsor Medical Monitor.

          -  Known hypersensitivity to prednisolone or prednisone, or to any of the excipients.

          -  Having a disease in which treatment with prednisolone or prednisone is not tolerated
             (including but not limited to osteoporosis with vertebral fractures, difficult to
             control hypertension, and difficult to control diabetes).

          -  Evidence of markers of potential underlying risk for autoimmune mediated hepatic
             disease:

               -  Anti-smooth muscle antibody assay results >=40 (Inova QUANTA LiteTM Actin IgG
                  enzyme-linked immunosorbent assay [ELISA]); values of 31 to 39 will be flagged as
                  possibly abnormal and the Investigator and Medical Monitor will evaluate the
                  participant for eligibility.

               -  Elevated anti-liver-kidney microsomal antibody type 1 (LKM1) titers.

               -  Total immunoglobulin G (IgG) >1.5*upper limit of normal (ULN).

               -  Antinuclear antibody (ANA) titer >1:320; OR ANA titer >1:80 if demonstrated
                  concurrently with alanine aminotransferase (ALT) that is >ULN.

          -  Active Hepatitis virus (Hepatitis C): As indicated by detectable hepatitis C virus
             (HCV) ribonucleic acid (RNA) by polymerase chain reaction (PCR).

          -  Hepatitis B: If surface antigen is positive.

          -  Seropositive for Human Immunodeficiency Virus (HIV).

          -  Receiving systemic antiviral and/or interferon therapy within 4 weeks prior to
             enrollment.

          -  Clinically significant infections (e.g. systemic fungal infections) requiring systemic
             treatment.

          -  Known immune disorder (including myeloma and lymphoma).

          -  Concurrent chemotherapy or biological therapy for treatment of neoplastic disease or
             other disorders.

          -  An absolute neutrophil count <1000 cells per cubic millimeter (cells/mm^3).

          -  Markers of hepatic inflammation or cirrhosis as evidenced by 1 or more of the
             following:

               -  Platelet count of <150,000/microliter (mcL).

               -  Serum albumin level is below the central laboratory's lower limit of normal and
                  FibroSURE is >=0.48 (i.e., Metavir staging of F2 or greater). Of note, in
                  participants with a known history of Gilbert's syndrome, a Fibrotest cannot be
                  used for fibrosis testing.

               -  Total bilirubin >1.5*ULN and direct bilirubin >=0.5 milligram per deciliter
                  (mg/dL).

               -  ALT or aspartate aminotransferase (AST) >1.0*ULN.

               -  Alkaline phosphatase (AP) >2.0*ULN.

               -  History of liver biopsy indicating moderate or severe fibrosis (Metavir staging
                  of F2 or greater).

               -  History of ascites, varices, variceal hemorrhage, or hepatic encephalopathy.

               -  Any findings on screening ultrasound that would preclude the safe use of AAV gene
                  therapy.

          -  Prothrombin time (PT) international normalized ratio (INR) >=1.4.

          -  Serum creatinine >1.5 mg/dL.

          -  Urine protein >30 mg/dL or >0.5 gram per day (g/day).

          -  Body mass index >38.

          -  Major surgery or an orthopedic surgical procedure planned within 6 months after
             enrollment.

          -  Acute or chronic disease that, in the opinion of the investigator, would adversely
             affect participant safety or compliance or interpretation of study results.

          -  Received an AAV vector previously or any other gene transfer agent in the previous 12
             months prior to Study Day 0.

          -  Received an investigational intervention or participated in another clinical trial
             within 4 weeks prior to enrollment or within 5 half-lives of the investigational drug
             administration, whichever is longer.

          -  Significant cardiovascular disease (such as New York Heart Association Class III or IV
             cardiac disease, congestive heart failure, myocardial infarction within the previous 6
             months, unstable arrhythmias, or unstable angina) or significant pulmonary disease
             (including obstructive pulmonary disease).

          -  Recent history of psychiatric illness or cognitive dysfunction (including drug or
             alcohol abuse) that in the opinion of the investigator, is likely to impair
             participants ability to comply with protocol mandated procedures.

          -  Participant is a family member or employee of the investigator.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 75 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? Entailment