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

Hemophilia A Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04541628
• Other study ID #: SIG-001-121
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: September 28, 2020
• Est. completion date: October 28, 2022

Study information

• Verified date: January 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 28, 2022
• Est. primary completion date: October 28, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hemophilia A

Intervention

Combination Product:
• SIG-001
Laparoscopic administration of SIG-001 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII.

Locations

Country	Name	City	State
United Kingdom	Clinical Study Site	London
United Kingdom	Clinical Study Site	Manchester
United Kingdom	Clinical Study Site	Southampton
United States	Clinical Study Site	Boston	Massachusetts
United States	Clinical Study Site	Indianapolis	Indiana
United States	Clinical Study Site	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Sigilon Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	FVIII activity levels assessed by one-stage and chromogenic assays overall and by dose/cohort.		From SIG-001 administration until study completion (5 years)
Secondary	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)
Secondary	Total number of replacement FVIII therapies administered overall and by dose/cohort.		From SIG-001 administration until study completion (5 years)