Clinical trial

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)

Name

SIG-005-121

Description

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.

Trial arms

Trial start

2021-11-15

Estimated PCD

2022-12-13

Trial end

2022-12-13

Status

Withdrawn

Phase

Early phase I

Treatment

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

Arms:

SIG-005

Primary endpoint

Number of patients with clinically significant changes from baseline in physical examination

Baseline up to 5 years

Number of patients with clinically significant changes in vital signs from baseline

Baseline up to 5 years

Number of patients with clinically significant changes in total (IgG) IDUA antibody titres from baseline

Baseline up to 5 years

Number of patients with clinically significant changes in clinical laboratory tests from baseline

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.

Baseline up to 5 years

Eligibility criteria

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)

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 0, 'type': 'ACTUAL'}}

Updated at

2023-04-11

1 organization

1 product

3 indications

Product

SIG-005

Indication

MPS I

Indication

Mucopolysaccharidosis type 1

Indication

MPS1-HS

Organization

Sigilon Therapeutics