Transplant Glomerulopathy
Conditions
Brief summary
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
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.
Interventions
DRUGActhar gel
Administration of the study drug in addition to the current maintenance immunosuppressive agents
Sponsors
University of Alabama at Birmingham
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety (Serious Adverse Events) | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Outcome | 1 year | composite of graft loss, death, decrease in eGFR\>10%, and increase in proteinuria |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Have Biopsy Proven Chronic Antibody Mediated Rejection, and Will Receive Acthar. In this cohort Acthar gel will be administered to all the enrolled patient with chronic AMR.
There is a single arm in this study.
Acthar gel: Administration of the study drug in addition to the current maintenance immunosuppressive agents | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | All Participants Have Biopsy Proven Chronic Antibody Mediated Rejection, and Will Receive Acthar. |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 54.5 Years |
| eGFR (estimated Glomerular Filtration Rate) | 49.2 ml/min/1.73 m^2 STANDARD_DEVIATION 14.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 6 participants |
| Serum Creatinine | 1.75 mg/dl STANDARD_DEVIATION 0.56 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
| Urine Albumin | 745 mg/L STANDARD_DEVIATION 771.5 |
| Urine Albumin Creatinine Ratio | 722.8 mg/g Creatinine STANDARD_DEVIATION 957.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 2 / 6 |
Outcome results
Primary
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.
Time frame: 12 months
Population: All participants were monitored for adverse events throughout their participation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Serious Adverse Events (SAE) | Safety (Serious Adverse Events) | 2 Participants |
Secondary
Efficacy Outcome
composite of graft loss, death, decrease in eGFR\>10%, and increase in proteinuria
Time frame: 1 year
Population: Study participants who received the study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Serious Adverse Events (SAE) | Efficacy Outcome | Composite outcome | 3 Participants |
| Serious Adverse Events (SAE) | Efficacy Outcome | Death | 1 Participants |
| Serious Adverse Events (SAE) | Efficacy Outcome | Decreased GFR>10% | 1 Participants |
| Serious Adverse Events (SAE) | Efficacy Outcome | Increased proteinuria | 1 Participants |