Safety & Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A

Study Overview
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Brief Summary
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SIG-001-121 is a first-in-human (FIH), phase 1/2, multi-centre, open-label, dose escalation study to assess the safety, tolerability, and preliminary efficacy of SIG-001 in adults with severe or moderately severe haemophilia A without inhibitors. Up to three dose cohorts (3 patients each) are planned. Cohort expansions (up to 3 additional patients) may be triggered to collect additional information about safety and efficacy.

Official Title
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A Phase 1/2 Open-Label, Dose-Escalation, Safety, Tolerability, and Efficacy Study of SIG-001 in Adult Patients With Severe or Moderately-Severe Haemophilia A Without Inhibitors (SIG-001-121)

Conditions
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Hemophilia A

Intervention / Treatment
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* Combination Product: SIG-001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males aged 18 years or older Diagnosis of Haemophilia A defined as ≤2% FVIII activity Greater than 150 exposure days to treatment with FVIII products Use of reliable barrier contraception if applicable Normal levels of von Willebrand factor (VWF) antigen Able and willing to provide informed consent Willing to withdraw from FVIII prophylaxis during specified periods in the study Exclusion Criteria: Body mass index (BMI) ≥35 Current FVIII inhibitors (>0.6 Nijmegen Bethesda Units/mL) or prior Immune Tolerance Induction (ITI) History of allergic reaction or anaphylaxis to recombinant FVIII products or SIG-001 components Evidence of any bleeding disorder in addition to haemophilia A Abnormal laboratory values as defined in the protocol Active infection with Hepatitis B or Hepatitis C virus or currently managed with antiviral medications for Hepatitis B or C Uncontrolled HIV infection Active alcoholism or drug addiction during the 12 months before the screening visit Active malignancy or history of malignancy in the 5 years prior to study entry Participation in another investigational medicine or device study Prior administration of a gene therapy product Significant underlying disease or comorbidities that are a contraindication for general anaesthesia or laparoscopic procedure

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SIG-001<br>B-Domain Deleted Human Factor VIII (BDD-hFVIII) Producing Spheres | Combination Product: SIG-001<br>* Laparoscopic administration of SIG-001 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and proportion of participants with treatment emergent adverse events (TEAEs) overall and by dose/cohort. |  | From SIG-001 administration until study completion (5 years) | 
| Number and proportion of participants with serious treatment emergent adverse events (TEAEs) overall and by dose/cohort. |  | From SIG-001 administration until study completion (5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and proportion of participants with inhibitor titer values assessed by Nijmegen Bethesda Assay overall and by dose/cohort. |  | From SIG-001 administration until study completion (5 years) | 
| FVIII activity levels assessed by one-stage and chromogenic assays overall and by dose/cohort. |  | From SIG-001 administration until study completion (5 years) | 
| Annualized Bleeding Rate (ABR) for all bleeds following SIG-001 administration presented by bleed type and location. |  | From SIG-001 administration until study completion (5 years) | 
| Total number of replacement FVIII therapies administered overall and by dose/cohort. |  | From SIG-001 administration until study completion (5 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Haemophilia A, Cell therapy, Gene therapy