- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05665036
Safety and Efficacy of Encapsulated Allogeneic MPS-1 Therapy
April 10, 2023 updated by: Sigilon Therapeutics, Inc.
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.
Study Overview
Status
Withdrawn
Intervention / Treatment
Study Type
Interventional
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Porto Alegre, Brazil
- Clinical Study Site
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London, United Kingdom, NW3 2QG
- Clinical Study Site
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Salford, United Kingdom
- Clinical Study Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: SIG-005
SIG-005 is comprised of human native alpha-L-iduronidase enzyme (hIDUA) producing spheres
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Laparoscopic administration of SIG-005 spheres, an encapsulated allogeneic cell therapy genetically modified with a non-viral vector to produce hIDUA
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of patients with clinically significant changes from baseline in physical examination
Time Frame: Baseline up to 5 years
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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.
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Baseline up to 5 years
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Number of patients with clinically significant changes in vital signs from baseline
Time Frame: Baseline up to 5 years
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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.
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Baseline up to 5 years
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Number of patients with clinically significant changes in total (IgG) IDUA antibody titres from baseline
Time Frame: Baseline up to 5 years
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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
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Baseline up to 5 years
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Number of patients with clinically significant changes in clinical laboratory tests from baseline
Time Frame: Baseline up to 5 years
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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.
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Baseline up to 5 years
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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
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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.
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Baseline up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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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.
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Baseline up to 5 years
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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
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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.
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Baseline up to 5 years
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To evaluate and Characterize effect of SIG-005 MRI images of liver and spleen volume
Time Frame: Baseline up to 5 years
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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.
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Baseline up to 5 years
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To evaluate and Characterize effect of SIG-005 on cardiac measurements via electrocardiogram (ECG)
Time Frame: Baseline up to 5 years
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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.
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Baseline up to 5 years
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To assess the effect of SIG-005 on health assessment and health-related quality of life
Time Frame: Baseline up to 5 years
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The effect of SIG-005 on health and health-related quality of life will be measured as changes from baseline in responses to the 12-Item Short Form Health Survey (SF-12) and the 5-level EuroQuol EQ-5D-5L questionnaire
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Baseline up to 5 years
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Anticipated)
November 15, 2021
Primary Completion (Actual)
December 13, 2022
Study Completion (Actual)
December 13, 2022
Study Registration Dates
First Submitted
November 3, 2021
First Submitted That Met QC Criteria
December 16, 2022
First Posted (Actual)
December 27, 2022
Study Record Updates
Last Update Posted (Actual)
April 11, 2023
Last Update Submitted That Met QC Criteria
April 10, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Other Study ID Numbers
- SIG-005-121
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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