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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
2

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • United States
    • California
      • Torrance, California, United States, 90502
        • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • Humira
Other: Placebo
Saline placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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.
day 0 to week 16 of treatment with adalimumab versus placebo

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.
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)
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.
Day 0 to week 16 of treatment with adalimumab versus placebo
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.
Day 0 to week 16 of treatment with adalimumab versus placebo
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.
Day 0 to week 16 of treatment with adalimumab versus placebo

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2016

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 5, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 7, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 15, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 16, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 30535

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Clinical Study Report

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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