4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Open-label Study of Anakinra in MPS III

Open-label Study of Anakinra in MPS III

Study Description
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

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 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 : December 23, 2019
Estimated Primary Completion Date : October 2021
Estimated Study Completion Date : December 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: treatment
anakinra 100 mg subcutaneous once daily
 Biological: anakinra
anakinra single-use prefilled glass syringes
Other Name: Kineret
Outcome Measures
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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   4 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • MPS III
  • ≥ 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
Contacts and Locations

Locations
Layout table for location information
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
Investigators
Layout table for investigator information
Principal Investigator: Lynda Polgreen, MD, MS The Lundquist Institute at Harbor-UCLA Medical Center
Tracking Information
First Submitted Date  ICMJE July 1, 2019
First Posted Date  ICMJE July 12, 2019
Last Update Posted Date April 5, 2021
Actual Study Start Date  ICMJE December 23, 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2019) 		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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 11, 2019) 		multi-domain responder index (MDRI) - composite outcome [ Time Frame: within individual change over 8-week treatment period compared to change over 8-week observational period ]
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.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Open-label Study of Anakinra in MPS III
Official Title  ICMJE Open-label Pilot Study of the Effects of Anakinra in Mucopolysaccharidosis (MPS) III
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mucopolysaccharidosis III
Intervention  ICMJE Biological: anakinra
anakinra single-use prefilled glass syringes
Other Name: Kineret
Study Arms  ICMJE Experimental: treatment
anakinra 100 mg subcutaneous once daily
Intervention: Biological: anakinra
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 11, 2019) 		20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • MPS III
  • ≥ 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04018755
Other Study ID Numbers  ICMJE 31834-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Study Sponsor  ICMJE Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Collaborators  ICMJE
  • Cure Sanfilippo Foundation
  • Swedish Orphan Biovitrum
Investigators  ICMJE
Principal Investigator: Lynda Polgreen, MD, MS The Lundquist Institute at Harbor-UCLA Medical Center
PRS Account Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯