Mucopolysaccharidosis Type IPhase 1/2NCT02437253
Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI
A Phase 1/2 study testing Adalimumab in people with Mucopolysaccharidosis Type I and Mucopolysaccharidosis Type II, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Mucopolysaccharidosis Type I, Mucopolysaccharidosis Type II, Mucopolysaccharidosis Type VI
- What is being tested?
- Adalimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- May 2015to Jul 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 17Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
About this study
Official title: 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.
Read the 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.
- Conditions
- Mucopolysaccharidosis Type I, Mucopolysaccharidosis Type II, Mucopolysaccharidosis Type VI
- Being tested
- Adalimumab, Placebo
- Keywords
- Mucopolysaccharidosis, Inflammation, Tumor necrosis factor - alpha inhibitor
- Medical subject headings
- Mucopolysaccharidosis I, Mucopolysaccharidosis II, Mucopolysaccharidosis VI, Mucopolysaccharidoses, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabDrug
Also called Humira
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.
PlaceboOther
Saline placebo
| Study group | Role | What they receive |
|---|---|---|
| Adalimumab first, then Placebo | Experimental | 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. Receives: Drug: Adalimumab; Other: Placebo |
| Placebo first, then Adalimumab | Experimental | 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. Receives: Drug: Adalimumab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Children's Health Questionnaire - Parent Form 50 Bodily Pain Standardized Score
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.
Measured: day 0 to week 16 of treatment with adalimumab versus placebo
Secondary outcomes (4)
Children's Health Questionnaire - Parent Form 50 Physical Function (PF) Standardized Score
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.
Measured: 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)
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.
Measured: Day 0 to week 16 of treatment with adalimumab versus placebo
Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee
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.
Measured: Day 0 to week 16 of treatment with adalimumab versus placebo
Anti-ERT Antibodies
Anti-laronidase antibodies for subjects with MPS I. Anti-idursulfase antibodies for subjects with MPS II.
Measured: Day 0 to week 16 of treatment with adalimumab versus placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2015 (estimated)
- Study startMay 2015
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mucopolysaccharidosis Type IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lynda E Polgreen, MD, MS, Principal investigator, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02437253
- Sponsor's protocol ID
- 30535
- Status last verified
- May 2017
- First submitted
- 5 May 2015
- Last updated
- 15 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II and VI
- ClinicalTrials.gov ID
- NCT02437253
- Acronym / sponsor ID
- 30535
- Conditions
- Mucopolysaccharidosis Type I, Mucopolysaccharidosis Type II, Mucopolysaccharidosis Type VI
- Keywords
- Mucopolysaccharidosis, Inflammation, Tumor necrosis factor - alpha inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 7 May 2015 (estimated)
- Results
- Posted 15 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adalimumab first, then Placebo | Experimental | Drug: Adalimumab, Other: PlaceboParticipants 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. |
| Placebo first, then Adalimumab | Experimental | Drug: Adalimumab, Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdalimumabAlso: HumiraSubjects 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. | Drug | Adalimumab first, then Placebo, Placebo first, then Adalimumab |
| PlaceboSaline placebo | Other | Adalimumab first, then Placebo, Placebo first, then Adalimumab |
Primary outcome
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.
4 secondary outcomes
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
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
Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynda E Polgreen, MD, MS principal investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Adalimumab in people with Mucopolysaccharidosis Type I and Mucopolysaccharidosis Type II, run by Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Children's Health Questionnaire - Parent Form 50 Bodily Pain Standardized Score (time frame: day 0 to week 16 of treatment with adalimumab versus placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2017.