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

NCT04541628 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: SIG-001-121
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 6

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.

Conditions

Hemophilia A

Keywords

Haemophilia A; Cell therapy; Gene therapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay

  Baseline Up to 115 Weeks

• Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays

  Baseline Up to 115 Weeks

• 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.

• Total Number of Replacement FVIII Therapies

  Baseline Up to 115 weeks

Study Arms (1)

SIG-001

EXPERIMENTAL

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

Interventions

SIG-001 COMBINATION_PRODUCT

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

SIG-001

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Sigilon Therapeutics, Inc.: collaborator

Study Sites (6)

Clinical Study Site

Indianapolis, Indiana, 46260, United States

Location

Clinical Study Site

Boston, Massachusetts, 02116, United States

Location

Clinical Study Site

Seattle, Washington, 98104, United States

Location

Clinical Study Site

London, United Kingdom

Location

Clinical Study Site

Manchester, United Kingdom

Location

Clinical Study Site

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: September 9, 2020
• Study Start: September 28, 2020
• Primary Completion: October 28, 2022
• Study Completion: January 9, 2023
• Last Updated: September 4, 2024
• Results First Posted: September 4, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); GB (3)