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

Phase 1

Active, not recruiting

• Conditions: Mucopolysaccharidosis VI; Mucopolysaccharidosis I; Mucopolysaccharidosis II
• Interventions: Drug: Adalimumab Injection [Humira]; Drug: Saline Solution for Injection

• Registration Number: NCT03153319
• Lead Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-05-11
• Study First Submitted QC: 2017-05-11
• Study First Posted: 2017-05-15
• Study Start: 2017-06-05
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-18
• Last Update Posted: 2024-10-22
• Primary Completion: 2025-12
• Study Completion: 2026-06

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 14

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Open-label adalimumab	Adalimumab Injection [Humira]	Open-label extension of adalimumab dose
Adalimumab	Adalimumab Injection [Humira]	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.
Placebo	Saline Solution for Injection	Saline placebo comparator

Primary Outcome Measures

Name	Time	Method
Pain - 16 weeks	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
Adalimumab trough	32 weeks	Percentage of subjects who achieve a goal trough concentration of adalimumab with every other week dosing

Secondary Outcome Measures

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

Trial Locations

Locations (1)

The Lundquist Institute at Harbor-UCLA Medical Center; 🇺🇸 Torrance, California, United States