Safety and Efficacy of Encapsulated Allogeneic MPS-1 Therapy

NCT05665036 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: SIG-005-121
• Study Type: interventional
• Target: N/A
• Locations: 2 countries
• Sites: 3

Brief 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. 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.

Conditions

MPS I; MPS1-S; MPS1-HS

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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

  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.

  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.

  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

  Baseline up to 5 years

• To evaluate and Characterize effect of SIG-005 on glycosaminoglycans (GAG) levels in urine following administration of SIG-005.

  Baseline up to 5 years

• To evaluate and Characterize effect of SIG-005 MRI images of liver and spleen volume

  Baseline up to 5 years

• To evaluate and Characterize effect of SIG-005 on cardiac measurements via electrocardiogram (ECG)

  Baseline up to 5 years

Other Outcomes (1)

• To assess the effect of SIG-005 on health assessment and health-related quality of life

  Baseline up to 5 years

Study Arms (1)

SIG-005

EXPERIMENTAL

SIG-005 is comprised of human native alpha-L-iduronidase enzyme (hIDUA) producing spheres

Combination Product: SIG-005 (hIDUA Producing Spheres)

Interventions

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

SIG-005

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sigilon Therapeutics, Inc.: lead

Study Sites (3)

Clinical Study Site

Porto Alegre, Brazil

Location

Clinical Study Site

London, NW3 2QG, United Kingdom

Location

Clinical Study Site

Salford, United Kingdom

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

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: November 3, 2021
• First Posted: December 27, 2022
• Study Start: November 15, 2021
• Primary Completion: December 13, 2022
• Study Completion: December 13, 2022
• Last Updated: April 11, 2023

Record last verified: 2023-04

Locations

GB (2); BR (1)