Effects of Adalimumab in Mucopolysaccharidosis Types I, II and VI

NCT02437253 | Completed Phase 1 Results DMC

• 1 other identifier: 30535
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Mucopolysaccharidosis Type I; Mucopolysaccharidosis Type II; Mucopolysaccharidosis Type VI

Keywords

Mucopolysaccharidosis; Inflammation; Tumor necrosis factor - alpha inhibitor

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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)

  Day 0 to week 16 of treatment with adalimumab versus placebo

• Range of Motion - Bilateral Shoulder, Elbow, Hip, Knee

  Day 0 to week 16 of treatment with adalimumab versus placebo

• Anti-ERT Antibodies

  Day 0 to week 16 of treatment with adalimumab versus placebo

Study Arms (2)

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.

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.

Drug: Adalimumab; Other: Placebo

Interventions

Adalimumab DRUG

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.

Also known as: Humira

Adalimumab first, then Placebo; Placebo first, then Adalimumab

Placebo OTHER

Saline placebo

Adalimumab first, then Placebo; Placebo first, then Adalimumab

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center: lead

Study Sites (1)

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, 90502, United States

Location

MeSH Terms

Conditions

Mucopolysaccharidosis I; Mucopolysaccharidosis II; Mucopolysaccharidosis VI; Mucopolysaccharidoses; Inflammation

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Small pilot study of 2 participants.

Results Point of Contact

• Title: Dr. Lynda Polgreen (PI)
• Organization: Los Angeles Biomedical Research Institute at Harbor-UCLA

lpolgreen@labiomed.org

310-222-1961

Study Officials

• Lynda E Polgreen, MD, MS

  Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 7, 2015
• Study Start: May 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: September 15, 2017
• Results First Posted: September 15, 2017

Record last verified: 2017-05

Locations

US (1)