A Study of BAX 888 in Male Adults With Severe Hemophilia A

Study Identifier:
201501
ClinicalTrials.gov Identifier:
NCT03370172
EudraCT Identifier:
2015-005576-22
Unmapped

Study Details

Medical Condition
  • Hemophilia A
Study Drug
  • Drug: BAX 888
Date
Mar 2018 - Apr 2025
Phase 1
Phase 2
Phase 3
Phase 4
N/A
Patient Requirements
Sex: Male
Age: 18 - 75 Years years
Requirements Information
Inclusion and Exclusion 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.

Protocol Summary

This study is looking at how safe it is to switch from emicizumab to Mim8, in people with haemophilia A. Mim8 is a new medicine that is used to prevent bleeding episodes in people with haemophilia A. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected under the skin using a pen-injector either once every week, once every two weeks or once every month. The participants will be trained in using the pen injector. The participants can choose themselves, in collaboration with the study doctor how often they get Mim8 in this study. When the participant will get their first Mim8 injection depends on their current treatment with emicizumab. The participants will get their first Mim8 injection at Visit 2. Participants will have between 6 and 27 Mim8 injections. The total number of injections participants will have depends on their dosing frequency. The study will last for about 6-12 months. While taking part in this study, there are some restrictions about what medicine participant can use. The study doctor will tell the participants more about this. In case the participants experience bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor. Female participants cannot take part if they are pregnant, breast-feeding or plan to get pregnant during the study period.

Trial Locations

Location
Status
Location
Phoenix Childrens Hospital
Phoenix, Arizona, United States, 85016
Status
N/A
Location
Orthopaedic Hospital DBA Orthopaedic Hemophilia Treatment Center
Los Angeles, California, United States, 90007
Status
N/A
Location
UC Davis Medical Center
Sacramento, California, United States, 95817
Status
N/A
Location
University of Colorado Hemophilia & Thrombosis Center
Aurora, Colorado, United States, 80045
Status
N/A
Location
Mount Sinai Medical Center
New York, New York, United States, 10029
Status
N/A
Location
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Status
N/A
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