Clinical trial NCT05152732: Safety and Tolerability of VGB-R04 in Patients With Haemophilia B
Official title: Safety and Tolerability of VGB-R04 in Patients With Haemophilia B
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hemophilia B
Keywords: Hemophilia
AAV
safety
gene therapy
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2021-12-10
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B.

Detailed description: Hemophilia B is a genetic bleeding disorder caused by pathogenic variants (eg, mutations, deletion) in the FIX gene. HB patients have frequent and potentially life-threatening bleeding and often develop progressive physical disability and pain from chronic haemarthropathy. Current replacement therapy needs regular treatment in the life-long time, bringing heavy economic and social burdens.

VGB-R04 is a novel AAV vector carrying a high specific activity factor IX variant. This study is intended to evaluate the safety, tolerability and kinetics of a single IV infusion of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 6 weeks before administration of VGB-R04. All subjects will undergo 52(±2) weeks of safety observation and will be encouraged to enroll in an extension study to evaluate the long-term safety of VGB-R04 for a total of five years.

Eligibility criteria: Inclusion Criteria:

1. Male ≥18 years and ≤75years of age;
2. Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%);
3. At least 100 days exposure history to FIX;
4. Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
5. Have acceptable laboratory values:

   1. Hemoglobin ≥110 g/L;
   2. Platelets ≥100×10'9 cells/L;
   3. AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
   4. Bilirubin ≤3× ULN ;
   5. Creatinine ≤1.5× ULN.
6. No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
7. Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences;
8. Able to provide informed consent and comply with the requirements of the study.

Exclusion Criteria:

1. Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to:

   1. Preexisting diagnosis of portal hypertension;
   2. Splenomegaly;
   3. Encephalopathy;
   4. Reduction of serum albumin;
   5. Evidence of significant liver fibrosis;
2. Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
3. Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
4. Evidence of active hepatitis B virus infection (HBV-DNA \>103 IU/ml) or hepatitis C virus infection (HCV antigen and HCV-RNA positive);
5. Evidence of malignant tumours or those with a previous history of malignant tumours;
6. Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
7. Any immunodeficiency;
8. Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 4 weeks;
9. Have used glucocorticoids, immunosuppressive drugs, or antipsychotics within the last 3 months;
10. Previous history of hypersensitivity or allergic reaction to any FIX products or any immunoglobulin;
11. Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
12. Any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Baseline up to Week 52
measure: Incidence of serious adverse events
timeFrame: Baseline up to Week 52
measure: Number of Participants with Clinically Significant Change from Baseline in Vital Signs
timeFrame: Baseline up to Week 52
measure: Number of Participants with Clinically Significant Change From Baseline in Physical Examination Findings
timeFrame: Baseline up to Week 52
measure: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Vector- derived FIX:C Activity
timeFrame: Baseline up to Week 52
measure: Vector- derived FIX antigen levels
timeFrame: Baseline up to Week 52
measure: Annualized bleeding rate changes from baseline
timeFrame: Baseline up to Week 52
measure: Annualized FIX consumption changes from baseline
timeFrame: Baseline up to Week 52
measure: Number of target joints
timeFrame: Baseline up to Week 52
measure: Vector shedding of VGB-R04
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Blood diseases hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: