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

• ClinicalTrials.gov Identifier: NCT03153319
• Recruitment Status: Recruiting
• First Posted: May 15, 2017
• Last Update Posted: February 10, 2021
• 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 or II.

Condition or disease	Intervention/treatment	Phase
Mucopolysaccharidosis I; Mucopolysaccharidosis II	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 or II. Children and adults diagnosed with MPS I or II, 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 and II
• Actual Study Start Date: June 5, 2017
• Estimated Primary Completion Date: December 2021
• Estimated Study Completion Date: October 2022

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 or II;
• 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@labiomed.org

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

Locations

United States, California

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center; Recruiting

Torrance, California, United States, 90502

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

Contact: Eva Villa-Lopez 310-357-9023 EVilla@labiomed.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; Lundquist Institute for Biomedical Innovation 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: February 10, 2021
• Last Verified: February 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; 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