Study to Evaluate the Safety and Efficacy of Adalimumab in MPS I, II, and VI

Phase 1/2 Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II, and VI

Randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI.

Study Overview

• Status: Active, not recruiting
• Conditions: Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI
• Intervention / Treatment: Drug: Adalimumab Injection [Humira]; Drug: Saline Solution for Injection

Detailed Description

This study is a randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI. Children and adults diagnosed with MPS I, II or VI, with significant joint restrictions and pain will be randomized to adalimumab treatment or placebo treatment for the first 16 weeks. This will be followed by a 32-week open label adalimumab treatment phase.

• Study Type: Interventional
• Enrollment (Anticipated): 14
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Adolfo Morales; Phone Number: 310-357-9023; Email: adolfo.morales@lundquist.org
• Study Contact Backup: Name: Eva Villa-Lopez; Phone Number: 310-357-9023; Email: EVilla@lundquist.org

Study Locations

• United States
  • California
    • Torrance, California, United States, 90502
      • The Lundquist Institute at Harbor-UCLA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female ≥5 years of age;
• Diagnosis of MPS I, II or VI;
• Treatment with ERT for ≥1 year or no treatment with ERT for ≥1 year;
• Weight ≥15 kg;
• Significant bodily pain reported by the CHQ-PF50 or SF-36 (> 1 SD more severe [below] than the general population mean);
• ≥ 3 joints with limitations in motion; and Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided.

Exclusion Criteria:

• History of HCT less than 2 years prior to enrollment;
• Immune suppression therapy less than 1 year prior to enrollment;
• Active graft versus host disease;
• Current diagnosis or history of lymphoma or other malignancy;
• Current active infection;
• History of serious opportunistic infection (e.g., bacterial [Legionella and Listeria]; tuberculosis [TB]; invasive fungal infections; or viral, parasitic, and other opportunistic infections);
• Positive TB skin test, positive Quantiferon-TB Gold TB test, positive chest X-ray, or a recent exposure to TB
• Congestive heart failure defined by an ejection fracture <50% measured by ECHO;
• Demyelinating disorders (e.g., central nervous system [CNS] disorders including multiple sclerosis and optic neuritis and peripheral nervous system disorders including Guillain-Barre syndrome);
• Hematologic abnormalities (e.g., pancytopenia, aplastic anemia);
• Hepatitis B infection (active or chronic carrier);
• Latex sensitivity;
• Pregnancy or breastfeeding;
• Known or suspected allergy to adalimumab or related products;
• Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment;
• Requirement for live vaccine exposure that would be expected to occur during the time frame of the study; or
• Any other social or medical condition that the Investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adalimumab; 20 mg subQ every other week (weight 15to <30 kg) 40 mg subQ every other week (weight ≥30 kg). Non-responders will be escalated to weekly dosing.	Drug: Adalimumab Injection [Humira]; Investigational Drug
Placebo Comparator: Placebo; Saline placebo comparator	Drug: Saline Solution for Injection; Placebo Comparator
Experimental: Open-label adalimumab; Open-label extension of adalimumab dose	Drug: Adalimumab Injection [Humira]; Investigational Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain - 16 weeks	Mean difference in bodily pain measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50) or the Medical Outcomes Study - Short Form 36 (SF-36) in treatment versus placebo at 16 weeks	16 weeks
Adalimumab trough	Percentage of subjects who achieve a goal trough concentration of adalimumab with every other week dosing	32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Joint range-of-motion - 16 weeks	Percentage of subjects who achieve a 5 degree or more improvement in joint range-ot-motion in treatment versus placebo at 16 weeks.	16 weeks
Pain - 52 weeks	Mean difference in bodily pain measured by the CHQ-PF50 or the SF-36 at 52 weeks compared to baseline.	52 weeks
Joint range-of-motion - 52 weeks	Percentage of subjects who achieve a 5 degree or more improvement in joint range-ot-motion at 52 weeks compared to baseline.	52 weeks
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability	Percentage of subjects who develop an AE and/or SAE	52 weeks

Collaborators and Investigators

• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Investigators: Principal Investigator: Lynda Polgreen, MD, The Lundquist Institute at Harbor-UCLA Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2017
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: May 11, 2017
• First Posted (Actual): May 15, 2017

Study Record Updates

• Last Update Posted (Actual): March 21, 2023
• Last Update Submitted That Met QC Criteria: March 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Mucopolysaccharidosis II; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Anti-Inflammatory Agents; Antirheumatic Agents; Adalimumab
• Other Study ID Numbers: 31041-01

Drug and device information, study documents

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