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Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI

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ClinicalTrials.gov Identifier: NCT02437253
Recruitment Status : Completed
First Posted : May 7, 2015
Results First Posted : September 15, 2017
Last Update Posted : September 15, 2017
Sponsor:
Information provided by (Responsible Party):
Los Angeles Biomedical Research Institute

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.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type I Mucopolysaccharidosis Type II Mucopolysaccharidosis Type VI Drug: Adalimumab Other: Placebo Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II and VI
Study Start Date : May 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : July 2016


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.
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 Name: Humira

Other: Placebo
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.
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 Name: Humira

Other: Placebo
Saline placebo




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. 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.

  2. 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.

  3. Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee [ Time Frame: Day 0 to week 16 of treatment with adalimumab versus placebo ]
    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.

  4. Anti-ERT Antibodies [ Time Frame: Day 0 to week 16 of treatment with adalimumab versus placebo ]
    Anti-laronidase antibodies for subjects with MPS I. Anti-idursulfase antibodies for subjects with MPS II.



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Ages Eligible for Study:   5 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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);
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02437253


Locations
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United States, California
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
Sponsors and Collaborators
Los Angeles Biomedical Research Institute
Investigators
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Principal Investigator: Lynda E Polgreen, MD, MS Los Angeles Biomedical Research Institute

Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site

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Responsible Party: Los Angeles Biomedical Research Institute
ClinicalTrials.gov Identifier: NCT02437253     History of Changes
Other Study ID Numbers: 30535
First Posted: May 7, 2015    Key Record Dates
Results First Posted: September 15, 2017
Last Update Posted: September 15, 2017
Last Verified: May 2017

Keywords provided by Los Angeles Biomedical Research Institute:
Mucopolysaccharidosis
Inflammation
Tumor necrosis factor - alpha inhibitor

Additional relevant MeSH terms:
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Mucopolysaccharidosis II
Mucopolysaccharidoses
Mucopolysaccharidosis I
Mucopolysaccharidosis VI
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