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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Hemophilia A
• Intervention / Treatment: Combination product: SIG-001

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Clinical Study Site
  • Manchester, United Kingdom
    • Clinical Study Site
  • Southampton, United Kingdom
    • Clinical Study Site
• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Clinical Study Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02116
      • Clinical Study Site
  • Washington
    • Seattle, Washington, United States, 98104
      • Clinical Study Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SIG-001; Participants received a single dose of 50 milliliter (mL), 78.5 mL and 133 mL of SIG-001 spheres [an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce B-Domain Deleted Human Factor VIII (BDD-hFVIII) producing Spheres] administered laparoscopically into the peritoneal cavity.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Number of Participants with at least one TEAEs are reported. A summary of other nonserious adverse events (AEs), and all serious adverse events (SAE's), regardless of causality, is located in the Reported Adverse Events section.	Baseline Up to 115 Weeks
Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs)	Number of Participants with at least one serious TEAEs are reported. A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.	Baseline Up to 115 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay	Development of FVIII inhibitors is measured using the Nijmegen Bethesda inhibitor assay. The assay measures inhibitors to BDD-FVIII and also other forms of FVIII in the plasma, although rFVIII-BDD was used as a calibrator.	Baseline Up to 115 Weeks
Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays	The change from baseline in FVIII activity, as measured by one-stage and chromogenic assays) is summarized.	Baseline Up to 115 Weeks
Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration	The annualized number of bleeds per participant (annualized bleeding rate) is calculated as the number of bleeding events divided by length of time on study product follow-up, in years. The duration of assessment for this outcome measure was two years and three months, and Year 3 includes only the three-month part of this study period.	Time Frame: Pre-infusion (bleeding events in 12 months prior to sphere placement), 1 year, 2 year and 3-year post-infusion (post sphere placement) from SIG-001 administration annualized up to 115 Weeks.
Total Number of Replacement FVIII Therapies	Number of doses after prophylaxis discontinued is reported.	Baseline Up to 115 weeks

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Sigilon Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2020
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): January 9, 2023

Study Registration Dates

• First Submitted: August 21, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): September 4, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Cell therapy; Gene therapy; Haemophilia A
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A
• Other Study ID Numbers: SIG-001-121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No