MPS IPhase 1/2NCT05665036
Safety and Efficacy of Encapsulated Allogeneic MPS-1 Therapy
A Phase 1/2 study testing SIG-005 (hIDUA Producing Spheres) in people with MPS I and MPS1-S, run by Sigilon Therapeutics, Inc. at 3 sites in 2 countries.
Trial summary
SIG-005-121 is a FIH, Phase 1/2, multi-centre, open-label, sequential dose-escalating study to assess the safety, tolerability, and preliminary efficacy of SIG-005 in adults with MPS-1. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- SIG-005 (hIDUA Producing Spheres)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 15 Nov 2021to 13 Dec 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Able and willing to provide informed consent
- Male or female aged 18 or older
- Diagnosis of attenuated MPS-1 (Hurler-Scheie or Scheie)
- Alpha-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range
- Prior treatment with ERT
- Willing to transition from ERT to SIG-005
- Female patients of childbearing potential with negative pregnancy test
- Use of highly effective method of contraception if applicable
Who cannot join
- A diagnosis of severe MPS-1
- Previous haematopoietic stem cell transplantation (HSCT)
- History of elevated total (IgG) anti-IDUA antibody
- Use of assistive respiratory devices
- Unable to walk independently
- History of allergic reaction or anaphylaxis to recombinant hIDUA
Show all 17Show fewer
- Body mass index (BMI) ≥35
- History of abdominal adhesions, medical history of Crohn's disease, inflammatory bowel disease or any disease that increases the risk of post-operative abdominal adhesions
- Significant underlying disease or comorbidities that are a contraindication for general anaesthesia or laparoscopic procedure
- Pregnant or lactating patients
- Prior administration of a gene therapy product
- Participation in another investigational medicine or device study
- Abnormal laboratory values as defined in the protocol
- 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
- Recent COVID-19 infection: within 60 days of recovery from infection
- Vaccination(s) within the last 60 days (including vaccines for SARS-CoV-2/COVID- 19)
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United Kingdom2 sites
Clinical Study Site
London, NW3 2QG
Clinical Study Site
Salford
About this study
Official title: A Phase 1/2 Open-Label, Sequential Dose-Escalation, Safety, Tolerability and Efficacy Study of SIG-005 in Adult Patients With Mucopolysaccharidoses 1 (MPS-1)
SIG-005-121 is a FIH, Phase 1/2, multi-centre, open-label, sequential dose-escalating study to assess the safety, tolerability, and preliminary efficacy of SIG-005 in adults with MPS-1. The study will evaluate up to three ascending dose levels of SIG-005 in male and female patients with attenuated MPS-1 (Scheie or Hurler-Scheie), 18 years of age or greater, who received Enzyme Replacement Therapy (ERT) for a minimum of 12 months prior to the study entry. Each cohort will include 3 patients.
- Being tested
- SIG-005 (hIDUA Producing Spheres)
- Medical subject headings
- Mucopolysaccharidosis I
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIG-005 (hIDUA Producing Spheres)Combination product
Laparoscopic administration of SIG-005 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce hIDUA
| Study group | Role | What they receive |
|---|---|---|
| SIG-005 | Experimental | SIG-005 is comprised of human native alpha-L-iduronidase enzyme (hIDUA) producing spheres Receives: Combination Product: SIG-005 (hIDUA Producing Spheres) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with clinically significant changes from baseline in physical examination
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in physical examination as assessed by an assessment of general appearance (head, eyes, ears, nose, and throat), as well as review of cardiovascular, dermatologic, gastrointestinal, genitourinary, lymphatic, musculoskeletal, neurologic and respiratory systems. Directed physical examinations at protocol-specified visits will be based on the patient's clinical status and will include general appearance, cardiovascular, gastrointestinal, neurologic, and respiratory assessments. Clinically significant changes from baseline will be captured as AEs.
Measured: Baseline up to 5 years
Number of patients with clinically significant changes in vital signs from baseline
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in vital signs, including temperature, respiratory rate, seated blood pressure, and pulse.
Measured: Baseline up to 5 years
Number of patients with clinically significant changes in total (IgG) IDUA antibody titres from baseline
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in total (IgG) antibody titres against IDUA
Measured: Baseline up to 5 years
Number of patients with clinically significant changes in clinical laboratory tests from baseline
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in clinical laboratory tests, including hematology, serum chemistry, and urinalysis.
Measured: Baseline up to 5 years
Number of patients with clinically significant changes in treatment-emergent adverse events (TEAE) from baseline, as assessed by CTCAE v5.0.
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in TEAEs as assessed by CTCAE v5.0.
Measured: Baseline up to 5 years
Secondary outcomes (4)
To evaluate and Characterize effect of SIG-005 in levels of α-L-iduronidase (IDUA) in blood after administration of SIG-005
To evaluate and characterize levels of IDUA and leukocyte count in blood plasma from time of baseline up to 5 years post-administration of SIG-005.
Measured: Baseline up to 5 years
To evaluate and Characterize effect of SIG-005 on glycosaminoglycans (GAG) levels in urine following administration of SIG-005.
Total GAG, HS and DS levels in urine and any clinically significant changes will be assessed from time of baseline up to 5 years post-administration of SIG-005.
Measured: Baseline up to 5 years
To evaluate and Characterize effect of SIG-005 MRI images of liver and spleen volume
Non-contrast MRI of the liver and spleen will be performed to determine any clinically significant changes in liver or spleen volume from time of baseline up to 5 years post-administration of SIG-005.
Measured: Baseline up to 5 years
To evaluate and Characterize effect of SIG-005 on cardiac measurements via electrocardiogram (ECG)
Resting 12-lead ECG assessments will be performed to determine any clinically significant changes in cardiac measurements from time of baseline up to 5 years post-administration of SIG-005.
Measured: Baseline up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2022
- Study start15 Nov 2021 (estimated)
- Primary completion13 Dec 2022
- Study completion13 Dec 2022
Why it stopped: Sponsor developing new product
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MPS IStudies of the same condition, open and under way.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sigilon Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05665036
- Sponsor's protocol ID
- SIG-005-121
- Status last verified
- Apr 2023
- First submitted
- 3 Nov 2021
- Last updated
- 11 Apr 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-Label, Sequential Dose-Escalation, Safety, Tolerability and Efficacy Study of SIG-005 in Adult Patients With Mucopolysaccharidoses 1 (MPS-1)
- ClinicalTrials.gov ID
- NCT05665036
- Acronym / sponsor ID
- SIG-005-121
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor developing new product
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sigilon Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Nov 2021 (estimated)
- Primary completion
- 13 Dec 2022 (actual)
- Study completion
- 13 Dec 2022 (actual)
- First posted
- 27 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SIG-005-121 is a FIH, Phase 1/2, multi-centre, open-label, sequential dose-escalating study to assess the safety, tolerability, and preliminary efficacy of SIG-005 in adults with MPS-1. The study will evaluate up to three ascending dose levels of SIG-005 in male and female patients with attenuated MPS-1 (Scheie or Hurler-Scheie), 18 years of age or greater, who received Enzyme Replacement Therapy (ERT) for a minimum of 12 months prior to the study entry. Each cohort will include 3 patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIG-005 | Experimental | Combination Product: SIG-005 (hIDUA Producing Spheres)SIG-005 is comprised of human native alpha-L-iduronidase enzyme (hIDUA) producing spheres |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Able and willing to provide informed consent
- Male or female aged 18 or older
- Diagnosis of attenuated MPS-1 (Hurler-Scheie or Scheie)
- Alpha-L-iduronidase enzyme activity level of less than 10% of the lower limit of the normal range
- Prior treatment with ERT
Key exclusion criteria (17 listed)
- A diagnosis of severe MPS-1
- Previous haematopoietic stem cell transplantation (HSCT)
- History of elevated total (IgG) anti-IDUA antibody
- Use of assistive respiratory devices
- Unable to walk independently
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-005 (hIDUA Producing Spheres)Laparoscopic administration of SIG-005 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce hIDUA | Combination product | SIG-005 |
Primary outcome
Number of patients with clinically significant changes from baseline in physical examination
Time frame: Baseline up to 5 years
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in physical examination as assessed by an assessment of general appearance (head, eyes, ears, nose, and throat), as well as review of cardiovascular, dermatologic, gastrointestinal, genitourinary, lymphatic, musculoskeletal, neurologic and respiratory systems. Directed physical examinations at protocol-specified visits will be based on the patient's clinical status and will include general appearance, cardiovascular, gastrointestinal, neurologic, and respiratory assessments. Clinically significant changes from baseline will be captured as AEs.
Number of patients with clinically significant changes in vital signs from baseline
Time frame: Baseline up to 5 years
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in vital signs, including temperature, respiratory rate, seated blood pressure, and pulse.
Number of patients with clinically significant changes in total (IgG) IDUA antibody titres from baseline
Time frame: Baseline up to 5 years
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in total (IgG) antibody titres against IDUA
Number of patients with clinically significant changes in clinical laboratory tests from baseline
Time frame: Baseline up to 5 years
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in clinical laboratory tests, including hematology, serum chemistry, and urinalysis.
Number of patients with clinically significant changes in treatment-emergent adverse events (TEAE) from baseline, as assessed by CTCAE v5.0.
Time frame: Baseline up to 5 years
Safety and tolerability will be assessed by evaluating the number of patients with clinically significant changes from baseline in TEAEs as assessed by CTCAE v5.0.
4 secondary outcomes
To evaluate and Characterize effect of SIG-005 in levels of α-L-iduronidase (IDUA) in blood after administration of SIG-005
Time frame: Baseline up to 5 years
To evaluate and Characterize effect of SIG-005 on glycosaminoglycans (GAG) levels in urine following administration of SIG-005.
Time frame: Baseline up to 5 years
To evaluate and Characterize effect of SIG-005 MRI images of liver and spleen volume
Time frame: Baseline up to 5 years
To evaluate and Characterize effect of SIG-005 on cardiac measurements via electrocardiogram (ECG)
Time frame: Baseline up to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2023.
- Individual participant dataSharing planned: Undecided
Related trials for MPS I
Active, not recruitingObservational study
Evaluation of Intravenous Laronidase Pharmacokinetics Before and After Hematopoietic Cell Transplantation in Patients With Mucopolysaccharidosis Type IH.
Hematopoietic Cell Transplantation, Mucopolysaccharidosis Type I
Active, not recruitingPhase 2
MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
Mucopolysaccharidosis Disorders, Hurler Syndrome
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Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
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A Phase I/II Trial of JR-446 in Mucopolysaccharidosis Type IIIB (MPS IIIB)
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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.
3 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-005 (hIDUA Producing Spheres) in people with MPS I and MPS1-S, run by Sigilon Therapeutics, Inc. at 3 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 8 inclusion and 17 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: withdrawn, as of the sponsor's last update on 11 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom, Brazil. 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?
The study was withdrawn before enrolling participants, so there are no results.
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 patients with clinically significant changes from baseline in physical examination (time frame: Baseline up to 5 years). The study lists 5 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 11 Apr 2023.