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

• ClinicalTrials.gov Identifier: NCT03153319
• Recruitment Status: Recruiting
• First Posted: May 15, 2017
• Last Update Posted: August 10, 2022
• Sponsor: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• Information provided by (Responsible Party): Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI	Drug: Adalimumab Injection [Humira]; Drug: Saline Solution for Injection	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II, and VI
• Actual Study Start Date: June 5, 2017
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: February 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Pain - 16 weeks [ Time Frame: 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
2. Adalimumab trough [ Time Frame: 32 weeks ]
   Percentage of subjects who achieve a goal trough concentration of adalimumab with every other week dosing

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Adolfo Morales; 310-357-9023; adolfo.morales@lundquist.org

Contact: Eva Villa-Lopez; 310-357-9023; EVilla@lundquist.org

Locations

United States, California

The Lundquist Institute at Harbor-UCLA Medical Center; Recruiting

Torrance, California, United States, 90502

Contact: Adolfo Morales 310-357-9023 adolfo.morales@lundquist.org

Contact: Eva Villa-Lopez 310-357-9023 EVilla@lundquist.org

Principal Investigator: Lynda Polgreen, MD, MS

Sponsors and Collaborators

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Investigators

• Principal Investigator: Lynda Polgreen, MD; The Lundquist Institute at Harbor-UCLA Medical Center

More Information

• Responsible Party: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
• ClinicalTrials.gov Identifier: NCT03153319
• Other Study ID Numbers: 31041-01
• First Posted: May 15, 2017
• Last Update Posted: August 10, 2022
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Mucopolysaccharidosis II; Mucopolysaccharidoses; Mucopolysaccharidosis I; Mucopolysaccharidosis VI; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Metabolic Diseases; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Adalimumab; Anti-Inflammatory Agents; Antirheumatic Agents