Clinical trial NCT05442528: Lead-in Study of VGB-R04 Gene Therapy for Hemophilia B-- An Observational Survey Analysis Study
Official title: Six-month lead-in Study to Collect Prospective Efficacy and Safety Data of Current Replacement Therapy in Adult Hemophilia B Patients -- An Observational Survey Analysis Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hemophilia B
Lead sponsor: Shanghai Vitalgen BioPharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-07-05
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hemophilia B (baseline FIX activity ≤ 2% of normal)

Brief summary: This is a prospective, open, multicenter, observational lead-in study，to collect prospective efficacy and safety data of current replacement therapy in adult hemophilia B patients.

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 is a prospective, open, multicenter, observational lead-in study. To evaluate the efficacy and safety of current treatment regiments in patients with moderate to severe HB (FIX:C activity ≤2%). The efficacy and safety data collected in this study may be used as baseline data for subsequent related clinical trials of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 4 weeks. All subjects will undergo 26 weeks of efficacy and safety observation .Eligible subjects will be invited to a key clinical study（phase 2 study）of VGB-R04,and then encouraged to enroll in an Long-term follow-up 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 ≤65years of age;
2. Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal);
3. At least 50 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 ≥100×109 /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;

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. Novel coronavirus infection occurred in the 6 weeks prior to entry into the group
5. Evidence of active hepatitis B virus infection (HBsAg positive) or hepatitis C virus infection (HCV-RNA positive);
6. Evidence of malignant tumours or those with a previous history of malignant tumours;
7. Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
8. Any immunodeficiency;
9. planned surgery may be required within one year;
10. Past thromboembolic events (arterial or venous thromboembolic events);
11. Hypertensive patients with poor blood pressure control (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥90mmHg after antihypertensive drug treatment);

Primary outcomes:
measure: Annualized bleeding rate changes from baseline
timeFrame: Baseline up to Week 26
Secondary outcomes:
measure: Annualized FIX consumption changes from baseline
timeFrame: Baseline up to Week 26
measure: Total number of annualized bleeding
timeFrame: Baseline up to Week 26
measure: FIX:C activity level.
timeFrame: Baseline up to Week 26
measure: Number of target joints
timeFrame: Baseline up to Week 26
measure: The incidence of adverse Events of special interest
timeFrame: Baseline up to Week 26
Other outcomes:
Locations:
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang
role: PRINCIPAL_INVESTIGATOR
References: