Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine, Metabolic, Metabolic, Metabolic |
| Therapuetic Areas: | Endocrinology, Pharmacology / Toxicology |
| Healthy: | No |
| Age Range: | 5 - Any |
| Updated: | 4/21/2016 |
| Start Date: | May 2015 |
| End Date: | May 2017 |
| Contact: | Lynda E Polgreen, MD, MS |
| Email: | lpolgreen@labiomed.org |
| Phone: | 310-222-1961 |
Pilot Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II and VI
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.
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.
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.
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.
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.
We found this trial at
1
site
Torrance, California 90502
Principal Investigator: Lynda Polgreen, MD, MS
Phone: 310-222-1961
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