Clinical trial NCT04541628: Safety & Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Hemophilia A
Keywords: Haemophilia A
Cell therapy
Gene therapy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Sigilon Therapeutics, Inc.
First posted: 2020-09-09
Enrollment: 3
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline Up to 115 Weeks
measure: Number of Participants With Serious Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline Up to 115 Weeks
Secondary outcomes:
measure: Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay
timeFrame: Baseline Up to 115 Weeks
measure: Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays
timeFrame: Baseline Up to 115 Weeks
measure: Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration
timeFrame: 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.
measure: Total Number of Replacement FVIII Therapies
timeFrame: Baseline Up to 115 weeks
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Clinical Study Site
state: Indiana
city: Boston
country: United States
facility: Clinical Study Site
state: Massachusetts
city: Seattle
country: United States
facility: Clinical Study Site
state: Washington
city: London
country: United Kingdom
facility: Clinical Study Site
city: Manchester
country: United Kingdom
facility: Clinical Study Site
city: Southampton
country: United Kingdom
facility: Clinical Study Site
Study officials:
References: