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

A Phase III, Single Arm, Cross-over, Multicenter Clinical Trial to Compare Efficacy and Safety of YW17(Laronidase; CinnaGen) Versus Laronidase (Aldurazyme®; Genzyme, BioMarin) in Patients With Mucopolysaccharidosis Type I (MPS I)"

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).

Study Overview

• Status: Completed
• Conditions: Mucopolysaccharidosis Type 1
• Intervention / Treatment: Drug: Antihistamine; Drug: Antipyretic; Biological: Laronidase

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Mashhad, Iran, Islamic Republic of
    • Clinical Research Development Unit of Akbar Hospital, Faculty of Medicine
  • Tehran, Iran, Islamic Republic of
    • Growth and Development Research Center, Childrens Medical Center
  • Tehran, Iran, Islamic Republic of
    • Loghman Hospital
  • Tehran, Iran, Islamic Republic of
    • Mofid Childrens Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aldurazyme®; Aldurazyme® (2.9 mg/5 mL), is administered 0.58 mg/kg weekly.	Drug: Antihistamine; An antihistamine is administered one hour before the infusion.; Drug: Antipyretic; An antipyretic is administered one hour before the infusion.; Biological: Laronidase; Laronidase as Aldurazyme® (the first 12 weeks) or YW17 (the second 12 weeks) is administered.
Experimental: YW17 (laronidase biosimilar); YW17 (2.9 mg/5 mL) produced by CinnaGen Company, is administered 0.58 mg/kg weekly.	Drug: Antihistamine; An antihistamine is administered one hour before the infusion.; Drug: Antipyretic; An antipyretic is administered one hour before the infusion.; Biological: Laronidase; Laronidase as Aldurazyme® (the first 12 weeks) or YW17 (the second 12 weeks) is administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean uGAG	urinary glycosaminoglycan	Baseline, weeks 8, 10, 12, 20, 22, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mean 6MWT	6-minute walking test	Baseline, week 12, week 24
mean predicted FVC	Forced vital capacity	Baseline, week 12, week 24
mean enzyme activity level	Enzyme activity assay	Weeks 11 and 23
Number of participants with adverse events	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.	During the study period (screening visit up to week 24)

Collaborators and Investigators

• Sponsor: Cinnagen
• Investigators: Principal Investigator: Ali Rabani, Professor, Professor of Pediatric Endocrinology & Metabolism, Department of Pediatrics

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2022
• Primary Completion (Actual): August 12, 2023
• Study Completion (Actual): November 18, 2023

Study Registration Dates

• First Submitted: April 27, 2024
• First Submitted That Met QC Criteria: May 5, 2024
• First Posted (Actual): May 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 4, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Mucopolysaccharidosis type I; Urinary Glycosaminoglycans; Laronidase; Aldurazyme®
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Mucopolysaccharidosis I; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Histamine H1 Antagonists; Histamine Antagonists; Antipyretics
• Other Study ID Numbers: CIN.LAR.AR.III.97

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No