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

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).

Study Overview

• Status: Terminated
• Conditions: Transplant Glomerulopathy
• Intervention / Treatment: Drug: Acthar gel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama School of Medicine, Alabama Transplant Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Unniversity of Maryland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Maryland, Baltimore
• Collaborators: University of Alabama at Birmingham
• Investigators: Principal Investigator: Abdolreza Haririan, MD, MPH, University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): May 27, 2021
• Study Completion (Actual): May 27, 2021

Study Registration Dates

• First Submitted: April 10, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 3, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenocorticotropic Hormone; Melanocyte-Stimulating Hormones; beta-Endorphin
• Other Study ID Numbers: HP-00063872

Drug and device information, study documents

• 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.: Yes