Safety and Efficacy of Encapsulated Allogeneic MPS-1 Therapy

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.

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)