Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI

Mucopolysaccharidosis Type I Clinical Trial

Official title:

Pilot Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II and VI

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02437253
• Other study ID #: 30535
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: May 5, 2015
• Last updated: January 8, 2016
• Start date: May 2015
• Est. completion date: May 2017

Study information

• Verified date: January 2016
• Source: Los Angeles Biomedical Research Institute
• Contact: Lynda E Polgreen, MD, MS
• Phone: 310-222-1961
• Email: lpolgreen[@]labiomed.org
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to collect preliminary data on whether the drug adalimumab (also called Humira) can decrease pain and stiffness, improve quality of life, and is safe in people with mucopolysaccharidosis type I, II, or VI. In this study people will be randomly assigned to one of two groups. One group will be treated with adalimumab the first 16 weeks of the study and then with a saline injection for the last 16 weeks of the study. The other group will start with the saline injection for 16 weeks and then switch to adalimumab for the last 16 weeks. The study subject and the study doctor and study coordinator will not know what group a subject is in until the study is done. Adalimumab is given as an injection, just under the skin, every 2 weeks. Both groups will have blood drawn at a screening visit, and then 7 more times over the 32 week study. There will be safety labs done (liver and immune function tests). Other safety tests include a chest X-ray and screening for tuberculosis exposure - these will be done at the screening visit and later in the study if there is concern for tuberculosis exposure or a persistent cough. The following will also be done at screening, the first, middle, and last study visits: 1) a pregnancy test in all girls 8 and older, 2) questionnaires that ask about pain, how MPS impacts social and physical function, and other quality of life questions, 3) height and weight. Finally, a physical exam, that includes for children and adolescents a check of where they are in puberty, will be done by a study physician at the first, middle, and last visits. There are risks to taking adalimumab that include redness and pain where the injection is given, a decreased ability to fight off infections, and others. The safety tests are designed to identify and decrease the risk associated with adalimumab. The study physicians believe that the potential benefit of adalimumab on pain, quality of life, and other MPS related problems outweigh the potential risks of treatment.

Description:

This is a randomized, pilot study consisting of a 32-week, crossover, double-blind, placebo-controlled treatment phase of subjects with Mucopolysaccharidosis (MPS) types I, II or VI treated with enzyme replacement therapy (ERT) and/or hematopoietic cell transplantation (HCT). Subjects will be treated with adalimumab (group 1) or placebo (group 2) for 16 weeks (i.e., 8 doses) then cross over to the other group for 16 weeks. Subjects will be treated with adalimumab (20 mg [weight 15-<30 kg] or 40 mg [weight ≥30 kg] administered subcutaneously [subQ] every other week) or placebo for 16 weeks, then cross-over to the other group for 16 weeks. Laboratory evaluations and Children's Health Questionnaire - Parent Form 50 (CHQ-PF50) for subjects <18 years of age or the Medical Outcomes Study Short Form-36 (SF-36) for subjects ≥18 years will be assessed at Week 16 and 32 to evaluate early treatment safety and efficacy. Safety will be assessed with laboratory evaluations at 4, 8, 20, and 24 weeks after treatment initiation, and with study visits at week 16 and 32, Physical function will be measured by the CHQ-PF50/SF-36, joint range of motion (ROM), 6-minute walk test (6MWT), and strength testing (hand-grip dynamometer) at baseline, 16, and 32 weeks. Joint inflammation will be measured by serum markers at baseline, 16, and 32 weeks. Anthropometric measurements will also be performed at Baseline and 16 and 32 weeks.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 4
• Est. completion date: May 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of MPS I, II or VI;

• Treatment with ERT for =1 year or no ERT for =1 year;

• Weight =15 kg;

• Bodily pain reported by the CHQ-PF50 or SF-36 > 1 SD below 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 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Mucopolysaccharidoses
• Mucopolysaccharidosis I
• Mucopolysaccharidosis II
• Mucopolysaccharidosis Type I
• Mucopolysaccharidosis Type II
• Mucopolysaccharidosis Type VI
• Mucopolysaccharidosis VI

Intervention

Drug:
• Adalimumab
Subjects will be treated with adalimumab (20 mg [weight 15-<30 kg] or 40 mg [weight =30 kg] administered subcutaneously [subQ] every other week) or placebo for 16 weeks, then cross-over to the other group for 16 weeks.

Other:
• Placebo
Saline placebo

Locations

Country	Name	City	State
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Los Angeles Biomedical Research Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain measured by the CHQ-PF50 or SF-36		after 16 weeks of treatment with adalimumab versus placebo	No
Secondary	Physical function measured by the CHQ-PF50 or SF-36		after 16 weeks of treatment with adalimumab versus placebo	No
Secondary	Pain measured by the Pediatric Pain Questionnaire		after 16 weeks of treatment with adalimumab versus placebo	No
Secondary	Range of motion - shoulder, elbow, hip, knee		after 16 weeks of treatment with adalimumab versus placebo	No
Secondary	Anti-ERT antibodies		after 16 weeks of treatment with adalimumab versus placebo	No
Secondary	anti-dsDNA antibodies		after 16 weeks of treatment with adalimumab	Yes