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

Phase 1

Terminated

• Conditions: Hemophilia A
• Interventions: Combination Product: SIG-001

• Registration Number: NCT04541628
• Lead Sponsor: Eli Lilly and Company

Brief 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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-08-21
• Study First Submitted QC: 2020-09-01
• Study First Posted: 2020-09-09
• Study Start: 2020-09-28
• Primary Completion: 2022-10-28
• Study Completion: 2022-10-28
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-23
• Last Update Posted: 2024-01-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 3

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SIG-001	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Baseline Up to 115 Weeks	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.
Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs)	Baseline Up to 115 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays	Baseline Up to 115 Weeks	The change from baseline in FVIII activity, as measured by one-stage and chromogenic assays) is summarized.
Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay	Baseline Up to 115 Weeks	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.
Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration	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.	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.
Total Number of Replacement FVIII Therapies	Baseline Up to 115 weeks	Number of doses after prophylaxis discontinued is reported.

Trial Locations

Locations (1)

Clinical Study Site; 🇬🇧 Southampton, United Kingdom