Clinical trial NCT05441553: A Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
Official title: A Phase 1/2 Study to Evaluate the Safety and Efficacy of VGB-R04 in Adult Hemophilia B Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hemophilia B
Lead sponsor: Shanghai Vitalgen BioPharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-07-01
Enrollment: 26
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A multicenter, open, non-randomized, phase I/II, two-phase clinical study. The dose exploration phase was phase I, and the dose extension phase was phase II.

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 efficacy 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 weeks of safety observation and will be 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 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 ≥100×109 /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;
7. Agree to use reliable contraception until 2 consecutive samples are negative for vector sequences;

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: Incidence of adverse events
timeFrame: Baseline up to Week 52
measure: Incidence of serious adverse events
timeFrame: Baseline up to Week 52
measure: FIX:C Antigen Level at Steady State
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: FIX:C activity level
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
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Vitalgen Biopharma Co.,Ltd.
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lei Zhang, PhD
role: PRINCIPAL_INVESTIGATOR
References: