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出境医 / 临床实验 / Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease

Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease

Study Description
Brief Summary:
The researchers are testing adalimumab, a treatment which blocks tumor necrosis factor (TNF), to see if it changes levels of urine biomarker levels (TIMP1 and MCP1). The outcomes may help develop individualized treatment options for future patients with TNF driven Focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD).

Condition or disease Intervention/treatment Phase
FSGS MCD Focal Segmental Glomerulosclerosis Minimal Change Disease Drug: adalimumab Phase 2

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Precision Medicine Proof of Concept for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
Actual Study Start Date : October 2, 2019
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: adalimumab
Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously
 Drug: adalimumab
Adalimumab will be dosed based on weight
Other Name: Humira
Outcome Measures
Primary Outcome Measures :
  1. Change in urine MCP1/Cr levels [ Time Frame: Baseline, Week 10 ]
    Change measured by for enzyme-linked immunosorbent assay (ELISA) testing

  2. Change in urine TIMP1/Cr levels [ Time Frame: Baseline, Week 10 ]
    Change measured by for enzyme-linked immunosorbent assay (ELISA) testing


Secondary Outcome Measures :
  1. Incidence adverse events (AEs) [ Time Frame: Through study week 14 ]
    Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs.

  2. Percent change of estimated glomerular filtration rate (eGFR) [ Time Frame: Baseline, Week 10 ]
    Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.

  3. Percent change in Urine Protein Creatinine Ratio (UPC) [ Time Frame: Baseline, Week 10 ]
    Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.

  4. Proportion of participants achieving a nadir Urine Protein Creatinine Ratio (UPC) less than 1.5 g/g and at least a 40% reduction from baseline [ Time Frame: Week 10 ]
    Urine specimen


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   6 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Kidney biopsy confirmed Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
  • For Minimal Change Disease patients only, history of resistance to corticosteroid therapy
  • Qualifying archived biopsy tissue is available for testing of gene expression profiling
  • Increased urinary excretion of biomarkers of Tumor Necrosis Factor (TNF) activation (MCP1/Cr and/ or TIMP1/Cr) at study screening
  • eGFR>45 ml/min/1.73 m2 at screening
  • Urine protein:creatinine ratio ≥1.5 g/g at screening
  • Weight >15 kg
  • Stable therapy with angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and oral immunosuppression agents for at least 30 days prior to enrollment
  • Birth control use in females of child bearing potential
  • Informed consent and assent if applicable

Exclusion Criteria:

  • Kidney or other solid organ or bone marrow transplant recipient
  • Allergy or intolerance to investigational agent
  • Secondary Focal Segmental Glomerulosclerosis (FSGS)
  • Severe obesity
  • Live virus vaccine in the past 3 months
  • Malignancy, current or in the past 5 years
  • Active local or systemic bacterial, fungal or viral infection
  • Active or latent Hepatitis B, Hepatitis C, HIV, or tuberculosis
  • History of demyelinating disease, e.g. Multiple Sclerosis or Guillain-Barre
  • History of heart failure
  • Active liver disease
  • Systemic lupus erythematosus or ANA > 1:80
  • History of inflammatory bowel disease, e.g. ulcerative colitis or Crohns disease
  • Cyclophosphamide in past 90 days, Rituximab in the past 180 days
  • Pregnancy or nursing
  • Blood white blood cell count <4,500/mm3; Hg <9 g/dL; Platelet count <150,000/mm3 at enrollment. - Use of an erythropoiesis stimulating agent will not be an exclusion criterion.
  • Concurrent use of interleukin-1 antagonist (Anakinra), other TNF blocking agent, methotrexate or abatacept
  • Diabetes Mellitus
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Vivian Kurtz, MPH 734-232-4830 umkidneystudies@umich.edu

Locations
Layout table for location information
United States, Michigan
The University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Vivian Kurtz, MPH    734-232-4830    umkidneystudies@umich.edu   
Principal Investigator: Debbie Gipson, MS, MD         
United States, New York
New York University Recruiting
New York, New York, United States, 10003
Contact: Howard Trachtman, MD    914-563-1580 ext 646-501-2665    howard.trachtma@nyulangone.org   
Contact: Suzanne Vento, RN    646-501-2665 ext 646-501-2665    suzanne.vento@nyulangone.org   
Principal Investigator: Howard Trachtman, MD         
United States, North Carolina
Levine Children's Hospital/Atrium Health Recruiting
Charlotte, North Carolina, United States, 28207
Contact: Jennifer Lamothe, MHA, BSN       Jennifer.Lamothe@atriumhealth.org   
Contact: Susan Massengill, MD    704-381-8800    susan.massengill@atriumhealth.org   
Principal Investigator: Susan Massengill, MD         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: John R Sedor, MD    216-704-6426    sedorj@ccf.org   
Contact: John F O'Toole, MD    216-219-5901    otoolej@ccf.org   
Principal Investigator: John R Sedor, MD         
Sponsors and Collaborators
University of Michigan
New York University
Investigators
Layout table for investigator information
Study Director: Debbie Gipson, MS, MD University of Michigan
Tracking Information
First Submitted Date  ICMJE July 2, 2019
First Posted Date  ICMJE July 5, 2019
Last Update Posted Date November 25, 2020
Actual Study Start Date  ICMJE October 2, 2019
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Change in urine MCP1/Cr levels [ Time Frame: Baseline, Week 10 ]
    Change measured by for enzyme-linked immunosorbent assay (ELISA) testing
  • Change in urine TIMP1/Cr levels [ Time Frame: Baseline, Week 10 ]
    Change measured by for enzyme-linked immunosorbent assay (ELISA) testing
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2019)
  • Incidence adverse events (AEs) [ Time Frame: Through study week 14 ]
    Adverse events (AEs) include abnormal clinical laboratory tests and severe AEs.
  • Percent change of estimated glomerular filtration rate (eGFR) [ Time Frame: Baseline, Week 10 ]
    Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.
  • Percent change in Urine Protein Creatinine Ratio (UPC) [ Time Frame: Baseline, Week 10 ]
    Measured by a blood sample. Summarized descriptively, including baseline, follow-up and changes from baseline.
  • Proportion of participants achieving a nadir Urine Protein Creatinine Ratio (UPC) less than 1.5 g/g and at least a 40% reduction from baseline [ Time Frame: Week 10 ]
    Urine specimen
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
Official Title  ICMJE Precision Medicine Proof of Concept for Tumor Necrosis Factor Inhibition in Focal Segmental Glomerulosclerosis and Treatment Resistant Minimal Change Disease
Brief Summary The researchers are testing adalimumab, a treatment which blocks tumor necrosis factor (TNF), to see if it changes levels of urine biomarker levels (TIMP1 and MCP1). The outcomes may help develop individualized treatment options for future patients with TNF driven Focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • FSGS
  • MCD
  • Focal Segmental Glomerulosclerosis
  • Minimal Change Disease
Intervention  ICMJE Drug: adalimumab
Adalimumab will be dosed based on weight
Other Name: Humira
Study Arms  ICMJE Experimental: adalimumab
Adalimumab dose every other week (study weeks 0, 2, 4, 6, and 8), subcutaneously
Intervention: Drug: adalimumab
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 2, 2019) 		8
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date January 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Kidney biopsy confirmed Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
  • For Minimal Change Disease patients only, history of resistance to corticosteroid therapy
  • Qualifying archived biopsy tissue is available for testing of gene expression profiling
  • Increased urinary excretion of biomarkers of Tumor Necrosis Factor (TNF) activation (MCP1/Cr and/ or TIMP1/Cr) at study screening
  • eGFR>45 ml/min/1.73 m2 at screening
  • Urine protein:creatinine ratio ≥1.5 g/g at screening
  • Weight >15 kg
  • Stable therapy with angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and oral immunosuppression agents for at least 30 days prior to enrollment
  • Birth control use in females of child bearing potential
  • Informed consent and assent if applicable

Exclusion Criteria:

  • Kidney or other solid organ or bone marrow transplant recipient
  • Allergy or intolerance to investigational agent
  • Secondary Focal Segmental Glomerulosclerosis (FSGS)
  • Severe obesity
  • Live virus vaccine in the past 3 months
  • Malignancy, current or in the past 5 years
  • Active local or systemic bacterial, fungal or viral infection
  • Active or latent Hepatitis B, Hepatitis C, HIV, or tuberculosis
  • History of demyelinating disease, e.g. Multiple Sclerosis or Guillain-Barre
  • History of heart failure
  • Active liver disease
  • Systemic lupus erythematosus or ANA > 1:80
  • History of inflammatory bowel disease, e.g. ulcerative colitis or Crohns disease
  • Cyclophosphamide in past 90 days, Rituximab in the past 180 days
  • Pregnancy or nursing
  • Blood white blood cell count <4,500/mm3; Hg <9 g/dL; Platelet count <150,000/mm3 at enrollment. - Use of an erythropoiesis stimulating agent will not be an exclusion criterion.
  • Concurrent use of interleukin-1 antagonist (Anakinra), other TNF blocking agent, methotrexate or abatacept
  • Diabetes Mellitus
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 70 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vivian Kurtz, MPH 734-232-4830 umkidneystudies@umich.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04009668
Other Study ID Numbers  ICMJE HUM00147018
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

This trial will follow the publication and data sharing policies of the NEPTUNE study, www.NEPTUNE-study.org

Request for ancillary studies should be submitted through the project contact and will be reviewed by the project steering committee.

After the study is completed, data will be submitted to the Nephrotic Syndrome Study Network (NEPTUNE), an NIH funded consortium. Proposals to access the data will then be submitted via the NEPTUNE Ancillary Studies program (NEPTUNE-study.org). Following closure of NEPTUNE, the trial data will convey with the NEPTUNE date to the NIH/NIDDK repository and can be accessed through this mechanism following approval.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: At the latest, data will be shared with the NEPTUNE Data Analysis and Coordinating Center at the time of publication of final results or 24 months after transfer of samples or raw data sets.
Access Criteria:

While this study is open data requests from this study will need to seek approval from the trial steering committee.

Once the data is transferred to the NEPTUNE study, all study data will become part of the aggregate NEPTUNE data and available to NEPTUNE participant sites and other requesting third parties upon request. Subsequent access to these data will be governed by the NIH Office of Rare Diseases (ORD) data sharing policies.
URL: http://neptune-study.org/
Responsible Party Debbie Gipson, MD, University of Michigan
Study Sponsor  ICMJE University of Michigan
Collaborators  ICMJE New York University
Investigators  ICMJE
Study Director: Debbie Gipson, MS, MD University of Michigan
PRS Account University of Michigan
Verification Date November 2020

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

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