Hemophilia APhase 1/2NCT04541628
Safety & Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A
A Phase 1/2 study testing SIG-001 in people with Hemophilia A, run by Eli Lilly and Company at 6 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- SIG-001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 6 sitesin 2 countries
- Study dates
- 28 Sep 2020to 9 Jan 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
6 sites in 2 countries.
6 sites in 2 countries
United States3 sites
Clinical Study Site
Boston, Massachusetts, 02116
Clinical Study Site
Indianapolis, Indiana, 46260
Clinical Study Site
Seattle, Washington, 98104
United Kingdom3 sites
Clinical Study Site
London
Clinical Study Site
Manchester
Clinical Study Site
Southampton
About this study
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)
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
- Being tested
- SIG-001
- Keywords
- Haemophilia A, Cell therapy, Gene therapy
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIG-001Combination product
Laparoscopic administration of SIG-001 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Combination Product: SIG-001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Baseline Up to 115 Weeks
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline Up to 115 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2020
- Study start28 Sep 2020
- Primary completion28 Oct 2022
- Study completion9 Jan 2023
Why it stopped: SIG-001 programme terminated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Sigilon Therapeutics, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04541628
- Sponsor's protocol ID
- SIG-001-121
- Status last verified
- Aug 2024
- First submitted
- 21 Aug 2020
- Last updated
- 4 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04541628
- Acronym / sponsor ID
- SIG-001-121
- Conditions
- Hemophilia A
- Keywords
- Haemophilia A, Cell therapy, Gene therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: SIG-001 programme terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Collaborators
- Sigilon Therapeutics, Inc.
- Study start
- 28 Sep 2020 (actual)
- Primary completion
- 28 Oct 2022 (actual)
- Study completion
- 9 Jan 2023 (actual)
- First posted
- 9 Sep 2020 (actual)
- Results
- Posted 4 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIG-001 | Experimental | Combination Product: SIG-001Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SIG-001Laparoscopic administration of SIG-001 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce BDD-hFVIII. | Combination product | SIG-001 |
Primary outcome
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: 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)
Time frame: 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.
4 secondary outcomes
Number of Participants With Inhibitor Titer Values Assessed by Nijmegen Bethesda Assay
Time frame: Baseline Up to 115 Weeks
Change From Baseline in FVIII Activity Levels Assessed by One-stage and Chromogenic Assays
Time frame: Baseline Up to 115 Weeks
Number of Bleeding Events [Annualized Bleeding Rate (ABR)] for All Bleeds Following SIG-001 Administration
Time frame: 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
Time frame: Baseline Up to 115 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
6 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SIG-001 in people with Hemophilia A, run by Eli Lilly and Company at 6 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Emergent Adverse Events (TEAEs) (time frame: Baseline Up to 115 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.