Efficacy and Safety of YW17 (Laronidase-CinnaGen) Compared to Aldurazyme® in MPS I Patients

Phase 3

Completed

• Conditions: Mucopolysaccharidosis Type 1
• Interventions: Biological: Laronidase; Drug: Antihistamine; Drug: Antipyretic

• Registration Number: NCT06406153
• Lead Sponsor: Cinnagen

Brief Summary

The purpose of this phase III study is to assess the efficacy and safety of YW17 produced by CinnaGen Company compared to Aldurazyme® in mucopolysaccharidosis type I (MPS I) patients.

All patients receive Aldurazyme® for 12 weeks, followed by YW17 for another 12 weeks.

The primary outcome is the assessment of the maintenance of the mean uGAG levels at the end of each medication administration. The secondary outcomes are the assessment of 6-minute walking test (6MWT), predicted forced vital capacity (FVC), enzyme activity assay, and adverse events (AEs).

Detailed Description

This is a phase III, single-sequence, cross-over study to assess the efficacy and safety of YW17 produced by CinnaGen Company in comparison with Aldurazyme® in MPS I patients.

All patients receive 0.58 mg/kg of Aldurazyme® for 12 weeks and then receive 0.58 mg/kg of YW17 for another 12 weeks.

Premedication with antipyretics and/or antihistamines is administered for all patients one hour before the infusion.

The primary outcome is to compare the mean uGAG levels at weeks 8, 10, and 12 (related to Aldurazyme®) with the mean uGAG levels at weeks 20, 22, and 24 (related to YW17).

The secondary outcomes, including 6MWT and FVC are assessed at the beginning and the end of each medication administration. Enzyme activity is assessed at the end of each medication administration. Safety assessments are performed during the study.

Study Timeline

• Study Start: 2022-09-10
• Primary Completion: 2023-08-12
• Study Completion: 2023-11-18
• Study First Submitted: 2024-04-27
• Study First Submitted QC: 2024-05-05
• Study First Posted: 2024-05-09
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-04
• Last Update Posted: 2024-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Age 5-18
• Diagnosed with MPS I
• Signing informed consent form

Exclusion Criteria

• Prior bone marrow transplantation or being a candidate for receiving haematopoietic stem cell transplantation (HSCT)
• Prior tracheotomy
• Being naïve to laronidase
• Acute hydrocephalus
• Abnormal renal function determined by measuring serum creatinine and blood urea nitrogen (BUN) levels
• Any severe organic disease that is not associated with MPS I
• Known hypersensitivity to laronidase or components of the laronidase solution
• Presence of any medical condition or other circumstances that could significantly interfere with study compliance
• Pregnancy and lactation
• Administration of any investigational drug within 30 days before study enrollment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
YW17 (laronidase biosimilar)	Laronidase	YW17 (2.9 mg/5 mL) produced by CinnaGen Company, is administered 0.58 mg/kg weekly.
YW17 (laronidase biosimilar)	Antihistamine	YW17 (2.9 mg/5 mL) produced by CinnaGen Company, is administered 0.58 mg/kg weekly.
YW17 (laronidase biosimilar)	Antipyretic	YW17 (2.9 mg/5 mL) produced by CinnaGen Company, is administered 0.58 mg/kg weekly.
Aldurazyme®	Laronidase	Aldurazyme® (2.9 mg/5 mL), is administered 0.58 mg/kg weekly.
Aldurazyme®	Antihistamine	Aldurazyme® (2.9 mg/5 mL), is administered 0.58 mg/kg weekly.
Aldurazyme®	Antipyretic	Aldurazyme® (2.9 mg/5 mL), is administered 0.58 mg/kg weekly.

Primary Outcome Measures

Name	Time	Method
mean uGAG	Baseline, weeks 8, 10, 12, 20, 22, and 24	urinary glycosaminoglycan

Secondary Outcome Measures

Name	Time	Method
mean enzyme activity level	Weeks 11 and 23	Enzyme activity assay
mean 6MWT	Baseline, week 12, week 24	6-minute walking test
mean predicted FVC	Baseline, week 12, week 24	Forced vital capacity
Number of participants with adverse events	During the study period (screening visit up to week 24)	All reported AEs are classified based on the Medical Dictionary for Regulatory Activities (MedDRA) terms and are graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Trial Locations

Locations (4)

Loghman Hospital; 🇮🇷 Tehran, Iran, Islamic Republic of

Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine; 🇮🇷 Mashhad, Iran, Islamic Republic of

Growth and Development Research Center, Childrens Medical Center; 🇮🇷 Tehran, Iran, Islamic Republic of

Mofid Childrens Hospital; 🇮🇷 Tehran, Iran, Islamic Republic of