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

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Mucopolysaccharidosis II

Treatments: Drug: Adalimumab Injection [Humira]; Drug: Saline Solution for Injection

Study type: Interventional

Funder types: Other

Identifiers

NCT03153319

31041-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 14 estimated patients

Sex: All

Ages: 5+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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14 participants in 3 patient groups, including a placebo group

Adalimumab

Experimental group

Description:

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.

Treatment:

Drug: Adalimumab Injection [Humira]

Placebo

Placebo Comparator group

Description:

Saline placebo comparator

Treatment:

Drug: Saline Solution for Injection

Open-label adalimumab

Experimental group

Description:

Open-label extension of adalimumab dose

Treatment:

Drug: Adalimumab Injection [Humira]