Pilot Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II and VI
Overview
- Phase
- Phase 1
- Intervention
- Adalimumab
- Conditions
- Mucopolysaccharidosis Type I
- Sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Children's Health Questionnaire - Parent Form 50 Bodily Pain Standardized Score
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief 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.
Detailed 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.
Investigators
Eligibility Criteria
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);
Arms & Interventions
Adalimumab first, then Placebo
Participants first received Adalimumab 20 mg subQ every other week (weight 15 to \<30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks.
Intervention: Adalimumab
Adalimumab first, then Placebo
Participants first received Adalimumab 20 mg subQ every other week (weight 15 to \<30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks. Participants then received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks.
Intervention: Placebo
Placebo first, then Adalimumab
Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to \<30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Intervention: Adalimumab
Placebo first, then Adalimumab
Participants first received Placebo saline subQ (volume matching Adalimumab 20 mg or 40 mg subQ) every other week for 16 weeks. Participants then received Adalimumab 20 mg subQ every other week (weight 15 to \<30 kg) or 40 mg subQ every other week (weight ≥30 kg) for 16 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Children's Health Questionnaire - Parent Form 50 Bodily Pain Standardized Score
Time Frame: day 0 to week 16 of treatment with adalimumab versus placebo
Children's Health Questionnaire - Parent Form 50 bodily pain (BP) standardized score for participants \< 18 years of age. Range is from 0 to 100 (no units) and standardization if determined by comparison to healthy age matched children. Lower values mean increased pain. The difference of change in BP standardized score from day 0 to week 16 during adalimumab treatment minus change in BP standardized score from day 0 to week 16 during placebo treatment is reported.
Secondary Outcomes
- Children's Health Questionnaire - Parent Form 50 Physical Function (PF) Standardized Score(Day 0 to week 16 of treatment with adalimumab versus placebo)
- Pain Measured by the Visual Analog Scale (VAS) in the Pediatric Pain Questionnaire (PPQ)(Day 0 to week 16 of treatment with adalimumab versus placebo)
- Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee(Day 0 to week 16 of treatment with adalimumab versus placebo)
- Anti-ERT Antibodies(Day 0 to week 16 of treatment with adalimumab versus placebo)