Treatment of Chronic Antibody-mediated Rejection in Kidney Transplant With Acthar

Study Overview
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Brief Summary
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This is an open label safety and feasibility trial using Acthar® in addition to the investigators center-specific standard therapy, which could include increase in maintenance immunosuppression, high dose IVIG (intravenous immunoglobulin) (2 g/Kg), and/or Rituximab, in patients with chronic antibody-mediated rejection (CAMR).

Detailed Description
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Subjects will receive Acthar® 40 units twice a week subcutaneously for 2 weeks. If the drug is well tolerated the dose will be increased to 80 units twice a week for another 22 weeks. The patients will be maintained on their center-specific standard maintenance regimen, typically consisting of Tacrolimus, mycephenolate mofetil/Sodium, and prednisone. After screening for the inclusion/exclusion criteria, the patients will be consented and enrolled in the study. The initial visit and subsequent study-related visits at 4, 8, 12, 24, 36 and 52 weeks will include routine evaluation and physical examination and laboratory studies including CBC (complete blood count), electrolyte panel, eGFR, albumin, liver enzymes, and Calcineurin inhibitor (CNI)/sirolimus drug level, according to the center's standard of care. Donor-specific antibody (DSA) will be tested at week 24, and 52 and patients will undergo a biopsy at week 52, as a part of the investigators standard of care. The biopsies will be evaluated by light and electron microscopy using standard histological Banff criteria, and staining for CD68.

Official Title
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Treatment of Chronic Antibody-mediated Rejection in Kidney Transplant With Acthar

Conditions
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Transplant Glomerulopathy

Intervention / Treatment
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* Drug: Acthar gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Morphologic diagnosis of CAMR, by light &/or electron microscopy any time after transplantation Current or previously documented donor-specific antibody (DSA) and/or focal or diffuse peritubular capillary C4d staining by immunohistochemistry eGFR>25 ml/min Exclusion Criteria: Diagnosis of malignancy within a year prior to enrollment (except cured cutaneous basal cell or squamous cell carcinoma). Lack of evidence of antibody involvement Pregnancy, lactation, or refusal to use birth control in women of child bearing potential Active infection, or history of HIV History of liver or thoracic transplant

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acthar<br>The study cohort. In this cohort Acthar gel will be administered to the enrolled patient with chrnic AMR. | Drug: Acthar gel<br>* Administration of the study drug in addition to the current maintenance immunosuppressive agents<br>* Other names: ACTH (Adrenocorticotropic hormone);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (Serious Adverse Events) | Participants will be monitored for Serious Adverse Events, as follows (as described in ClinicalTrials.gov) Death, Life-threatening events, Hospitalization (initial or prolonged), Disability and events that requires intervention to prevent permanent impairment or damage. Other (non serious) events which were anticipated or unanticipated (as described in ClinicaTrials.gov) will be monitored. ASSESSMENT: The subjects will be assessed at regular intervals through a questionnaire for Acthar related events, physician evaluation at clinical visits, and self reporting. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Outcome | composite of graft loss, death, decrease in eGFR>10%, and increase in proteinuria | 1 year |