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Comparative and Efficacy Study of ACTHar Gel Alone or in Combination With Tacrolimus in Fibrillary Glomerulopathy (FACT)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04080076
Recruitment Status : Recruiting
First Posted : September 6, 2019
Last Update Posted : March 10, 2020
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
NephroNet, Inc.

Brief Summary:
A 1 treatment ACTHar gel

Condition or disease Intervention/treatment Phase
Renal Disease Fibrillary Glomerulopathy Drug: Acthar 80 UNT/ML Injectable Solution Drug: Oral Tab Tacrolimus Phase 4

Detailed Description:

This is a multicenter, Phase 4, prospective, open labeled study to compare the safety, tolerability, and efficacy of a 12month course of ACTHar The addition of tacrolimus to patients exhibiting a partial response to ACTH resulted in a further reduction in Fibrillary glomerulopathy.

:

Spe #1-will randomize with biopsy proven DNA-JB9 positive Fibrillary glomerulopathy to receive course of ACTHar gel at 80 units SQ 2X/week alone or in combination with oral Tacrolimus at 1.0 mg BID (targeting for trough Tacrolimus dose o

Hypothesis Treatment with combination ACTHar gel therapy will result in a higher eGFR after 24 months of follow up than patients randomized to ACTHar gel therapy alone

Hy3: Combination therapy of ACTHar Gel and Tacrolimus in patients with DNA-JB9 positive Fibrillary will lead to significantly lower urinary markers of podocyte injury compared t ACTHar gel therapy alone.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:

ACTHar gel alone-patients will be receive 80 units SQ Q 2X/week for 52 weeks

ACTH gel 80 units 2X per week plus oral Tacrolimus (1.0 mg BID) titrating to a trough level of 4-6 ng/ml for 52 weeks

Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Comparative Safety and Efficacy Study of ACTHar Gel Alone or in Combination With Oral Tacrolimus to Reduce Urinary Proteinuria in Patients With Idiopathic DNAJB9 Positive Fibrillary Glomerulopathy
Actual Study Start Date : March 24, 2019
Estimated Primary Completion Date : March 14, 2021
Estimated Study Completion Date : March 14, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: ACTHar gel
ACTHar gel alone-patients will be receive 80 units SQ Q 2X/week for 52 weeks
Drug: Acthar 80 UNT/ML Injectable Solution
ACTHar 80 Units SQ 42 x Week

Active Comparator: ACTHar gel combined with Tacrolimus
ACTH gel 80 units 2X per week plus oral Tacrolimus (1.0 mg BID) titrating to a trough level of 4-6 ng/ml for 52 weeks
Drug: Acthar 80 UNT/ML Injectable Solution
ACTHar 80 Units SQ 42 x Week

Drug: Oral Tab Tacrolimus
Oral Tab Tacrolimus (1.0 mg PO BID) in combination with ACTHar 80 Units SQ 42 X week




Primary Outcome Measures :
  1. change in UP/Cr ratio in patients with biopsy proven Fibrillary GN after treated with ACTHar gel alone OR in combination with oral Tacrolimus [ Time Frame: 12 months ]
    The change in UP/Cr ratio in patients with biopsy proven Fibrillary GN after 12 months of treatment with treated with ACTHar gel (80 units SQ 2X/week) alone OR in combination with oral Tacrolimus (1.0 mg PO BID). The change in UP/Cr for each group will also be compared to baseline UP/Cr ratios prior to randomization


Secondary Outcome Measures :
  1. relative change in UP/Cr [ Time Frame: 24 months ]
    The relative change in UP/Cr at 24 months (12 months after stopping both ACTH and Tacrolimus) in the ACTHar gel group and the ACTHar gel + Tacrolimus group.

  2. T that achieves complete, partial or clinical responses [ Time Frame: 12 months ]
    The percentage of patients in the ACTHar gel alone versus ACTHar gel + Tacrolimus group that achieves complete, partial or clinical responses after 12 months of therapy

  3. The change in eGFR (measured by CKD-EPI formula) between the ACTHar gel and ACTHar Gel + Tacrolimus groups [ Time Frame: 24 months ]
    The change in eGFR (measured by CKD-EPI formula) between the ACTHar gel and ACTHar Gel + Tacrolimus groups after 24 months of treatment with ACTHar gel alone or in combination with oral Tacrolimus. In addition, we will also compare the relative change in eGFR between those patients receiving ACTHar gel alone with those randomized to combination therapy.

  4. To compare the change in urinary biomarkers with ACTHar gel alone or in combination with Tacrolimus. [ Time Frame: 12 months ]
    To compare the change in urinary biomarkers (see below) at baseline and after 12 months of treatment with ACTHar gel alone or in combination with Tacrolimus. The patients urinary biomarker levels after 12 months of therapy will be compared between the ACTHar gel alone group and ACTHar gel + Tacrolimus group. a) Urinary VEGF 121, 165 189, and206 b) Urinary MCP-1 c) Urinary Synaptopodin d) Urinary TGF-beta e) Urinary Podocalyxin f) Urinary Nephrin



Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Histologic Inclusion Criteria:

All patients with a diagnosis of The Fibrillary GN will be classified according to the Nasr nomenclature:

  1. Renal biopsy demonstrating DNA-JB9 Positive staining within 3 years of study randomization
  2. Mesangial expansion with/without glomerular sclerosis diffuse sclerosis

4) Crescents or endocapillary proliferation Note: Patients with > 50% interstitial fibrosis will not be eligible for study Note: Patients with monoclonal will not be eligible for study participation

Inclusion Criteria:

  1. Male/Female ag
  2. Biopsy proven Fibrillary GN wityears of study randomization
  3. Stable Maximum RAAS inhibition X 4 weeks prior to randomization Note: Maximum RAAS inhibition will be the discretion of the site PI
  4. eGFR > 25 mls/min calculate b formula
  5. UP/Cr ratio > 2000 mg/gm 5 Note: IF UP/Cr less than 2000 mg/gm, a formal urine collection for total protein can be performed. The total 24-hour will need to >/= 2000mg.
  6. Blood pressure targeted to < 140/90 at the time of randomization
  7. Patients with MGUS without history of myeloma WILL be eligible.
  8. Patients with monoclonal staining for fibrillary fibers will be excluded
  9. Patients with Type II non-insulin dependent diabetes WILL be eligible provided the renal biopsy does not show nodular Kimmelstiel Wilson lesions

Exclusion

  1. Patients with MGUS and history of myeloma WILL NOT be eligible
  2. Patients with active viral production of either B or C as evidence by historical PCR test positive for active viral shedding
  3. HIV seropositivity
  4. Renal biopsy data with > 50% Interstitial Fibrosis
  5. Patient with active or a known history
  6. Patients with insulin Dependent diabetes mellitus will be excluded Note: patients with T are well controlled WITHOUT the need for insulin WILL be eligible for the study.
  7. Patients with Type II non-insulin dependent diabetes WILL be eligible provided the renal biopsy does not show nodular Kimmelstiel Wilson lesions.
  8. Patients receiving steroids, MMF, cyc, Azathioprine or other immunosuppressive agent with of study random Note: Wash medications will be allowed at the screening visit
  9. Patients having received Rituximab or B cell modifying biologic therapy within 6 months of randomization

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): NCT04080076


Contacts
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Contact: James A. Tumlin, MD 770-490-9333 jamestumlinmdnephronet@gmail.com
Contact: Jeremy Whitson, CCRA, CCRP jwhitson@nephrosynergy.com

Locations
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United States, Georgia
Georgia Nephrology Research Institute Recruiting
Lawrenceville, Georgia, United States, 30046
Contact: James A Tumlin, MD, CCRP    770-490-5555    jamestumlinmdnephronet@gmai.com   
Contact: Jeremy Whitson, CCRA, CCRP    424-943-4265 ext 4239434265    jwhitson@synergy.com   
Sponsors and Collaborators
NephroNet, Inc.
Mallinckrodt
Investigators
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Study Director: James A. Tumlin, MD NephroNet, Inc.

Publications:

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Responsible Party: NephroNet, Inc.
ClinicalTrials.gov Identifier: NCT04080076    
Other Study ID Numbers: NN-002
First Posted: September 6, 2019    Key Record Dates
Last Update Posted: March 10, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Kidney Diseases
Urologic Diseases
Tacrolimus
Adrenocorticotropic Hormone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists