Clinical trial NCT05665036: Safety and Efficacy of Encapsulated Allogeneic MPS-1 Therapy
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: MPS I
MPS1-S
MPS1-HS
Lead sponsor: Sigilon Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Number of patients with clinically significant changes from baseline in physical examination
timeFrame: Baseline up to 5 years
measure: Number of patients with clinically significant changes in vital signs from baseline
timeFrame: Baseline up to 5 years
measure: Number of patients with clinically significant changes in total (IgG) IDUA antibody titres from baseline
timeFrame: Baseline up to 5 years
measure: Number of patients with clinically significant changes in clinical laboratory tests from baseline
timeFrame: Baseline up to 5 years
measure: Number of patients with clinically significant changes in treatment-emergent adverse events (TEAE) from baseline, as assessed by CTCAE v5.0.
timeFrame: Baseline up to 5 years
Secondary outcomes:
measure: To evaluate and Characterize effect of SIG-005 in levels of α-L-iduronidase (IDUA) in blood after administration of SIG-005
timeFrame: Baseline up to 5 years
measure: To evaluate and Characterize effect of SIG-005 on glycosaminoglycans (GAG) levels in urine following administration of SIG-005.
timeFrame: Baseline up to 5 years
measure: To evaluate and Characterize effect of SIG-005 MRI images of liver and spleen volume
timeFrame: Baseline up to 5 years
measure: To evaluate and Characterize effect of SIG-005 on cardiac measurements via electrocardiogram (ECG)
timeFrame: Baseline up to 5 years
Other outcomes:
measure: To assess the effect of SIG-005 on health assessment and health-related quality of life
timeFrame: Baseline up to 5 years
Locations:
city: Porto Alegre
country: Brazil
facility: Clinical Study Site
city: London
country: United Kingdom
facility: Clinical Study Site
city: Salford
country: United Kingdom
facility: Clinical Study Site
Study officials:
References: