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Open-label Study of Anakinra in MPS III

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04018755
Recruitment Status : Completed
First Posted : July 12, 2019
Last Update Posted : March 21, 2023
Cure Sanfilippo Foundation
Swedish Orphan Biovitrum
Information provided by (Responsible Party):
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Brief Summary:

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a disorder of metabolism, associated with insufficient production of a lysosomal enzyme needed for normal cell function. As a consequence of the cellular dysfunction, patients with this disorder develop progressive, irreversible neurodegeneration. Sadly, to date no evidence-based treatments are available.

Inflammation has been connected with disease pathogenesis in the MPS disorders. Therapies aimed at decreasing inflammation are currently being studied in many MPS disorders and benefits in both brain and other parts of the body have been reported.Decreasing interleukin-1 (IL-1) in an animal model of MPS III showed benefits in brain disease and behavior. Thus, we think that anakinra (Kineret), which decreases IL-1 levels in the body, will improve behavioral and other problems in children with MPS III.

Anakinra is approved by the FDA for treatment of rheumatoid arthritis (RA) and neonatal-onset multisystem inflammatory disease (NOMID). It is not approved for any MPS disorder.

The design of this study is an open-label, single center, pilot study of 20 participants with MPS III. There will be an initial screening visit, followed by an 8-week observational period, then a 36-week treatment period, and finally another 8-week observational period to determine any effects of withdrawal from the treatment.

During visits the participants will undergo a medical history, a physical examination, and anthropometric measurements. Blood, urine, and stool will be collected for biomarker levels and safety laboratory studies. Questionnaires will be completed with questions related to behavior, stooling, sleep, and activities of daily living. Seizure and movement disorders will be monitored as well.

The most common risks of receiving anakinra, based on RA and NOMID experience, include local injection site reactions, headache, nausea, vomiting, arthralgia, and flu-like symptoms. The most serious potential risk is a serious infection and neutropenia. However, because so few people with MPS have been treated with anakinra, all the risks related to MPS patients receiving anakinra are not currently known. Additional risks related to taking part in the study include some pain, bruising, and/or bleeding due to blood draws/peripheral IV placement, and discomfort with completing some of the questionnaires.

The expected potential direct benefits include, but are not limited to, improved behavior, sleep, stooling, communication, mood, and gait; as well as decreased seizure frequency, disordered movement and fatigue. However, there is no guarantee that participants will get any benefit from being in this study.

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis III Biological: anakinra Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-label Pilot Study of the Effects of Anakinra in Mucopolysaccharidosis (MPS) III
Actual Study Start Date : February 23, 2019
Actual Primary Completion Date : July 17, 2022
Actual Study Completion Date : March 8, 2023

Arm Intervention/treatment
Experimental: treatment
anakinra 100 mg subcutaneous once daily
Biological: anakinra
anakinra single-use prefilled glass syringes
Other Name: Kineret

Primary Outcome Measures :
  1. multi-domain responder index (MDRI) - composite outcome [ Time Frame: up to 8 weeks ]
    MDRI composite outcome comprised of the Sanfilippo Behavior Rating Scale, Children's Sleep Health Questionnaire, Autism Parent Stress Index, PROMIS fatigue survey, seizure log, movement disorder log, and Non-communicating Children's Pain Checklist - Revised. MDRI will be calculated as the sum of scores from the components. Subjects will receive a score for each component of the MDRI listed above. A score of 0 will be given for a change in score less than the Minimal Clinically Important Difference (MCID). A score of +1 (improvement) or -1 (worsening) will be given for a change in score of ≥ 1 MCID and < 2 times MCID. A score of +2 (improvement) or -2 (worsening) will be given for a change in score of ≥ 2 and <3 times MCID. A score of +3 (improvement) or -3 (worsening) will be given for a change in score of ≥ 3 times MCID.

Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ≥ 4 years of age
  • 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 when cognitively possible.
  • If on Genistein, must have been on a stable dose for 6 months prior to enrollment
  • If on melatonin or other sleep medications, must have been on stable doses for the past 3 months

Exclusion Criteria:

  • Currently enrolled in another ongoing clinical treatment trial
  • Previous or current treatment with anakinra, canakinumab or any other IL-1 inhibitor.
  • Use of the following therapies prior to enrollment:

    • Narcotic analgesics within 24 hours prior to enrollment.
    • Tocilizumab, dapsone or mycophenolate mofetil within 3 weeks prior to enrollment.
    • Etanercept, leflunomide, thalidomide, or cyclosporine or intraarticular, intramuscular, intravenous, or oral administration of glucocorticoids within 4 weeks prior to enrollment.
    • Intravenous immunoglobulin (IVIG), adalimumab, or methotrexate within 8 weeks prior to enrollment.
    • Infliximab, 6-mercaptopurine, azathioprine, cyclophosphamide or chlorambucil within 12 weeks prior to enrollment.
    • Rituximab within 26 weeks prior to enrollment
  • Live vaccines within 1 month prior to enrollment.
  • Known presence or suspicion of active, chronic or recurrent serious bacterial, fungal or viral infections, including tuberculosis, HIV infection or hepatitis B or C infection.
  • Clinical evidence of liver disease or liver injury as indicated by presence of abnormal liver tests:

    • AST or ALT > 5 x ULN, or
    • AST or ALT > 3 x ULN accompanied by elevated bilirubin >2 x ULN.
  • Presence of severe renal function impairment (estimated creatinine clearance < 30 mL/min/1.73m2).
  • Presence of neutropenia.
  • History of malignancy.
  • Known hypersensitivity to E coli-derived proteins, or any components of Kineret® (anakinra).
  • Pregnant or lactating women.
  • 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 Quantiferon-TB Gold TB test, positive chest X-ray, or a recent exposure to TB
  • Requirement for live vaccine exposure that would be expected to occur during the time frame of 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): NCT04018755

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United States, California
The Lundquist Institute at Harbor-UCLA Medical Center
Torrance, California, United States, 90502
Sponsors and Collaborators
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Cure Sanfilippo Foundation
Swedish Orphan Biovitrum
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Principal Investigator: Lynda Polgreen, MD, MS The Lundquist Institute at Harbor-UCLA Medical Center
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Responsible Party: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
ClinicalTrials.gov Identifier: NCT04018755    
Other Study ID Numbers: 31834-01
First Posted: July 12, 2019    Key Record Dates
Last Update Posted: March 21, 2023
Last Verified: March 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Connective Tissue Diseases
Metabolic Diseases
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents