Safety and Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A
- Conditions
- Haemophilia AMedDRA version: 20.0Level: LLTClassification code 10018937Term: Haemophilia ASystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-004210-33-GB
- Lead Sponsor
- Sigilon Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 18
1. Males aged 18 years or older
2. Diagnosis of Haemophilia A as follows:
a) Severe (<1% FVIII activity) receiving FVIII prophylaxis or on-demand treatment; or
b) Moderately-severe (=1% - =2% FVIII activity) receiving FVIII prophylaxis
3. Greater than 150 exposure days to treatment with FVIII products
4. Fertile males (not surgically sterilized) who have sexual partners that are women of childbearing potential must be willing to use a barrier method of contraception (e.g. condoms) for at least 90 days post-SIG-001 administration
5. Normal levels of von Willebrand factor (VWF) antigen (=50 IU/dL)
6. Able and willing to provide informed consent
7. Willing to withdraw from FVIII prophylaxis during specified periods in the study
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 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
1. Morbid obesity defined as body mass index (BMI) =35
2. Current FVIII inhibitors (>0.6 NBU/mL) or prior Immune Tolerance Induction (ITI)
Note: Patients with a history of low and/or transient inhibitors require Sponsor review and approval.
3. History of allergic reaction or anaphylaxis to recombinant FVIII products, alginate (including seaweed and algae), or barium and barium products (including barium contrast agents)
4. Evidence of any bleeding disorder in addition to haemophilia A
5. Abnormal laboratory values, as follows:
a) Platelet count <100 × 109/L
b) Creatinine =1.5 mg/dL
c) Haemoglobin <11 g/dL
d) Elevated levels (i.e. greater than 2 × upper limit of normal (ULN) of aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin
Note: Patients with a known history of Gilbert’s disease and bilirubin levels above ULN are not excluded.
6. Active infection with Hepatitis B or Hepatitis C virus, defined as a positive HBsAg, HBeAg, HBV DNA, or HCV RNA results, or currently managed with antiviral medications for Hepatitis B or C
7. Uncontrolled HIV infection, defined as CD4+ counts =200/µL or by a viral load of >200 copies/mL
8. Active alcoholism or drug addiction during the 12 months before the screening visit
9. Active malignancy or history of malignancy in the 5 years prior to study entry, exclusive of surgically removed non-melanoma skin cancer
10. Participation in another investigational medicine or device study within 90 days of screening or 5 investigational product half-lives, whichever is longer
11. Prior administration of a gene therapy product
12. Treatment with emicizumab less than 6 months prior to screening.
Note: Patients with emicizumab exposure may be eligible before 6 months of prior exposure if FVIII activity assessed by one stage assay is back to pre-emicizumab treatment levels.
13. Unable to tolerate general anaesthesia required for the laparoscopic procedure
14. History of:
a) Abdominal adhesions due to prior large, median laparotomy(ies)
Note: Uncomplicated prior laparoscopic procedures are not exclusionary (e.g. cholecystectomy, laparoscopic appendectomy or diagnostic laparoscopy).
b) Septic peritonitis
c) Intraperitoneal mesh
d) Inflammatory Bowel Disease (IBD), including ulcerative colitis or Crohn’s disease
15. Other comorbidities that in the opinion of the Investigator increase the risk of abdominal adhesions
16. Any disease or medical condition that in the Investigator’s opinion is a contraindication for anaesthesia or the laparoscopic procedure (e.g. prior significant cardiovascular events)
17. In the Investigator’s judgment, the patient is unlikely to complete all protocol-required study visits, procedures, or comply with the study requirements for participation
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of up to 3 dose levels of SIG-001 administered laparoscopically into the intraperitoneal space.;Secondary Objective: To evaluate development of FVIII inhibitors after administration of SIG-001<br>To characterize FVIII activity levels after administration of SIG-001<br>To assess frequency of bleeding episodes following SIG-001 administration<br>To assess effects of SIG-001 on usage of FVIII products;Primary end point(s): Clinically significant changes from baseline in vital signs, clinical laboratory tests, and treatment emergent adverse events (TEAE);Timepoint(s) of evaluation of this end point: Vitals – Screening, SIG-001 Administration, Follow-Up up to 5 years.<br>TEAEs – Screening, SIG-001 Administration, Follow-Up up to 5 years.<br>See Table 2 Schedule of Assessment in the Clinical Study Protocol for further details.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Factor VIII inhibitor titers (Nijmegen Bethesda Units [NBU])<br>FVIII activity levels (one-stage and chromogenic assays)<br>Bleeding rate (annualized; ABR)<br>Total use of factor VIII therapies (annualized);Timepoint(s) of evaluation of this end point: FVIII inhibitor titers - Screening 1, Follow Up up to 5 years.<br>FVIII activity levels - Screening 1, SIG-001 Administration, Follow-Up up to 5 years.<br>ABR and annualized FVIII therapy use - assessed prospectively throughout the study.<br>See Table 2 Schedule of Assessment in the Clinical Study Protocol for further details.<br>