- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02437253
Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI
August 16, 2017 updated by: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
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.
Study Overview
Status
Completed
Intervention / 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.
Study Type
Interventional
Enrollment (Actual)
2
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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Torrance, California, United States, 90502
- Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
5 years and older (ADULT, OLDER_ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: CROSSOVER
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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.
|
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 Names:
Saline placebo
|
EXPERIMENTAL: 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.
|
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 Names:
Saline placebo
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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day 0 to week 16 of treatment with adalimumab versus placebo
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Children's Health Questionnaire - Parent Form 50 Physical Function (PF) Standardized Score
Time Frame: Day 0 to week 16 of treatment with adalimumab versus placebo
|
Children's Health Questionnaire - Parent Form 50 physical function (PF) 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 decreased physical function.
The difference of change in PF standardized score from day 0 to week 16 during adalimumab treatment minus change in PF standardized score from day 0 to week 16 during placebo treatment is reported.
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Day 0 to week 16 of treatment with adalimumab versus placebo
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Pain Measured by the Visual Analog Scale (VAS) in the Pediatric Pain Questionnaire (PPQ)
Time Frame: Day 0 to week 16 of treatment with adalimumab versus placebo
|
Percent of participants with a >10 mm improvement in either "how you feel now" or "worst pain you had this week" on the VA in the PPQ during adalimumab versus during placebo by either parental or subject report.
Range is 0-100 mm; lower number means less pain.
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Day 0 to week 16 of treatment with adalimumab versus placebo
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Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee
Time Frame: Day 0 to week 16 of treatment with adalimumab versus placebo
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Number of joints with a >5 degree more positive change during 16 weeks of adalimumab versus 16 weeks of placebo.
A total of eight joints were measured.
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Day 0 to week 16 of treatment with adalimumab versus placebo
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Anti-ERT Antibodies
Time Frame: Day 0 to week 16 of treatment with adalimumab versus placebo
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Anti-laronidase antibodies for subjects with MPS I. Anti-idursulfase antibodies for subjects with MPS II.
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Day 0 to week 16 of treatment with adalimumab versus placebo
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2015
Primary Completion (ACTUAL)
July 1, 2016
Study Completion (ACTUAL)
July 1, 2016
Study Registration Dates
First Submitted
May 5, 2015
First Submitted That Met QC Criteria
May 5, 2015
First Posted (ESTIMATE)
May 7, 2015
Study Record Updates
Last Update Posted (ACTUAL)
September 15, 2017
Last Update Submitted That Met QC Criteria
August 16, 2017
Last Verified
May 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Genetic Diseases, Inborn
- Genetic Diseases, X-Linked
- Connective Tissue Diseases
- Carbohydrate Metabolism, Inborn Errors
- Metabolism, Inborn Errors
- Lysosomal Storage Diseases
- Mucinoses
- Mental Retardation, X-Linked
- Intellectual Disability
- Heredodegenerative Disorders, Nervous System
- Mucopolysaccharidosis II
- Mucopolysaccharidoses
- Mucopolysaccharidosis I
- Mucopolysaccharidosis VI
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Adalimumab
Other Study ID Numbers
- 30535
Plan for Individual participant data (IPD)
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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