Moderate/severe to severe hemophilia B MedDRA version: 19.0 Level: LLT Classification code 10060614 Term: Hemophilia B (Factor IX) System Organ Class: 100000004850
Conditions
Interventions
Product Code: DTX101
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not yet assigned
Other descriptive name: DTX101
Concentration unit: Other
Concentration type: not l
Sponsors
Dimension Therapeutics, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male =18 years of age. 2. Moderate/severe or severe hemophilia B (baseline FIX activity =2% of normal or documented history of FIX activity =2%). 3. At least 3 bleeding episodes per year that require on-demand treatment with FIX OR are treated with a prophylactic regimen of FIX. 4. At least 100 days exposure history to FIX. 5. No documented history of inhibitors (neutralizing antibodies) to exogenous FIX. 6. No known allergic reaction to exogenous FIX or any component of DTX101. 7. Willing to stop prophylactic treatment with recombinant FIX at specified time points during the study. 8. Willing and able to provide written informed consent. 9. Willing and able to comply with study procedures and requirements. 10. Willing to use effective contraception at the time of administration of DTX101 and for 3 months following administration of DTX101. Appropriate contraceptive methods include a condom with spermicide. Abstinence, defined as sexual inactivity, is an acceptable form of birth control; however, appropriate contraception must be used if the subject becomes sexually active. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 13 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. History of liver disease as evidenced by any of the following: portal hypertension, ascites, splenomegaly, esophageal varices, hepatic encephalopathy, or a liver biopsy with evidence of stage 3 fibrosis. 2. Significant hepatic inflammation or cirrhosis as evidenced by any of the following: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.0 × upper limit of normal (ULN), total bilirubin >1.5 × ULN, alkaline phosphatase (ALP) >2.5 × ULN, platelet count 1.5 × ULN. 3. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, documented by current use of antiviral therapy for HBV or HCV or by hepatitis B surface antigen (HBsAg) or HCV RNA positivity. NOTE: Two negative viral assays by polymerase chain reaction (PCR), collected at least 6 months apart, will be required to be considered negative for HCV. Subjects can be rescreened once if they have one negative sample and must wait to have the second sample collected within the following 6 months. 4. History of human immunodeficiency virus (HIV) infection AND any of the following: CD4+ cell count 200 copies/mL, on 2 separate occasions, as measured by PCR. 5. Anti-AAVrh10 neutralizing antibody titer >1:5. 6. Participation (current or previous) in another gene therapy study. 7. Participation in another investigational medicine study within 3 months before screening. 8. History of a malignancy for which the subject has received treatment in the past 2 years except for prostate cancer treated with watchful waiting or surgically removed non-melanoma skin cancer. 9. Has any other significant medical condition that the investigator feels would be a risk to the subject or would impede the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To determine the safety of single ascending intravenous (IV) doses of DTX101 in adults with moderate/severe to severe hemophilia B. - To establish a dose of DTX101 that achieves a peak plasma level of vector-derived factor IX (FIX) at 6 weeks after IV administration to allow further clinical development.;Secondary Objective: Secondary: - To assess the impact of DTX101 on the number of bleeding episodes requiring recombinant FIX infusion during the study. - To evaluate the kinetics, duration, and magnitude of plasma FIX activity, by dose, after IV administration of DTX101 in adults with hemophilia B. - To assess the impact of DTX101 on the frequency of FIX replacement therapy during the study. - To describe the immune response to the FIX transgene after IV administration of DTX101. - To assess the impact of DTX101 on the subject’s quality of life. Exploratory: - To describe the immune response to AAVrh10 capsid proteins after IV administration of DTX101.;Timepoint(s) of evaluation of this end point: 1. from the time the subject signs the ICF until their exit from the study 2. Week 6;Primary end point(s): 1. The incidence of adverse events (AEs), treatment-emergent AEs (TEAEs), and serious AEs (SAEs) will be summarized for each dosing cohort by severity and relationship to study product. 2. The change from baseline in FIX activity at Week 6 as determined by the activated partial thromboplastin time (aPTT) clot-based assay. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: 1. The annualized bleeding rate (ABR) will be calculated for all subjects through Week 52 (±1 week). 2. The time course of FIX activity, as determined by aPTT, will be summarized by time point and dose level of DTX101. 3. The annualized and average weekly use of FIX replacement therapy will be calculated for all subjects through Week 52 (±1 week). 4. The development of neutralizing antibodies to FIX (FIX inhibitor), as determined by a Bethesda assay, will be summarized by time point and dose level of DTX101. 5. The development of a cell-mediated immune response to FIX, as determined by enzyme-linked immunospot (ELISPOT) assay, will be summarized by time point and dose level of DTX101. 6. Responses to the EuroQol 5D 5 level (EQ-5D-5L™) and Haemophilia-Specific Quality of Life (Haem-A-QoL) will be summarized.;Timepoint(s) of evaluation of this end point: 1. Through Week 52 (±1 week) 2. At screening; Day 0 predose; Weeks 2, 4, 6, 8, 10, 12; once every four weeks from Week 16 to Week 52 3. Through Week 52 (±1 week) 4. At screening; Day 0 predose; Weeks 6, 8, 16, 32, 40, 48, 52 5. Day 0 predose; Weeks 6, 8, 16, 32, 40, 48, 52 6. Day 0 predose; Weeks 24, 36, 48 and 52 | — |
Countries
Bulgaria, France, Italy, United Kingdom, United States
Contacts
Public ContactClinical Development
Dimension Therapeutics, Inc.
Outcome results
None listed