Clinical trial NCT02115503: A Prospective, Global, Multi-center, Treatment Registry Study of Intravenous Immunoglobulin Maintenance Therapy in Alloantibody Positive Renal Allograft Recipients
Official title: A Prospective, Global, Multi-center, Treatment Registry Study of Intravenous Immunoglobulin Maintenance Therapy in Alloantibody Positive Renal Allograft Recipients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Renal Transplant Recipients With Anti-HLA Antibodies
Lead sponsor: Databean
Sponsor class: INDUSTRY
Collaborators: name: Octapharma
First posted: 2014-04-16
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Primary care clinic

Brief summary: The purpose of this treatment registry study is to determine if monthly infusions of Intravenous Immunoglobulin (IVIg) for 6 months will neutralize donor specific antibodies that are thought to be responsible for chronic rejection episodes in renal transplant subjects. 162 renal transplant subjects will receive IVIg 5% at 2gm/kg/month for 6 months and be followed for 3 years.


Eligibility criteria: Inclusion Criteria:

* Subject is 18 years of age or older
* Able to provide voluntary written informed consent
* Renal transplant recipient at least 1 month post-transplant
* On stable doses of maintenance immunosuppression for at least 14 days prior to study entry and remains on stable maintenance doses for the duration of the study
* Presence of DSA greater than or equal to 1000 mean fluorescence intensity (MFI) single antigen bead assay via Luminex (normalized 2,000 - 15,000 MFI, inclusive) measured within 6 months prior to consent
* Female subjects must be post-menopausal for at least 1 year, or surgically sterilized, or must agree to use two effective methods of birth control from the time of consent through 30 days after the last dose of IVIg.
* Male subjects must be surgically sterilized, or must agree to use two effective methods of birth control from the time of consent through 30 days after the last dose of IVIg
* Subject is compliant and intends to be available for follow-up study period of 3 years

Exclusion Criteria:

* Multi-organ transplant
* History of anaphylactic or severe systemic reactions to human immunoglobulin
* IgA deficient subjects with antibodies against IgA and a history of hypersensitivity
* Serum creatinine \> 3.0 mg/dL within 90 days prior to consent
* Recipients of ABO incompatible kidney transplants
* Acute rejection within 180 days (6 months) prior to consent defined as:

  1. Biopsy proven acute Cellular Rejection \[Banff grade I (including IA and IB), grade II (including IIA and IIB) or grade III\]; or
  2. an antibody-mediated rejection with C4d positivity, or
  3. chronic rejection with C4d positivity (C4d positivity is defined as staining diffuse in peritubular capillary area. Isolated C4d glomerular staining or C4d staining of \< 50% of the peritubular capillaries will not be exclusion criteria). Borderline cellular rejection will not be excluded (Banff 2005), or
  4. Clinical signs and symptoms of acute rejection including elevated creatinine, fever over 100 degrees, pain or tenderness around the transplanted kidney, fluid retention of the hands, legs, feet, ankles or eyelids, sudden weight gain (2-4 pounds in a day, or 5 pounds or more in a week), decrease in urine output with the same amount of fluid intake, or dark yellow or orange urine output, flu-like symptoms, such as chills, aches, tiredness, dizziness, nausea, loss of appetite, weakness, fatigue, vomiting or general sense of not feeling well (Note: NOT all signs and symptoms need to be present to document acute rejection)
* Evidence of proteinuria (\> 3 grams) within 90 days (3 months) prior to consent
* Active CMV+ or EBV+ viremia that requires, or will require, anti-viral therapy
* History of HCV, HIV and/or HBsAg positivity
* History of post-transplant lymphoproliferative disease.
* Active BK/polyomavirus nephropathy, or BK/polyomavirus nephritis that requires, or will require, anti-viral therapy (not prophylactic)
* Recipients of a kidney from a donor who tests positive for HIV, HBsAg or anti-HCV.
* History of malignancy within the past 5 years that is not considered to be cured, with the exception of complete resection of localized basal cell carcinoma of the skin (excised ≥ 1 years prior to enrollment).
* Subjects who are receiving everolimus, sirolimus or azathioprine as immunosuppressive agents and who are unwilling, or unable, to change to mycophenolate mofetil or mycophenolic acid within 14 days prior to consent
* White blood cell count of \<1,000/mm3 within 90 days prior to consent
* Platelet count \<60,000/mm3 within 90 days prior to consent
* Evidence of severe liver disease with abnormal liver profile (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] \> 3 times upper limit of normal \[ULN\]) within 90 days prior to consent
* Total bilirubin \> 1.5 times ULN within 90 days prior to consent
* Post-transplant history of cardiovascular disease within 180 days (6 months) prior to consent defined as:

  1. Electrocardiographic evidence of MI,
  2. Electrocardiographic evidence of acute ischemia,
  3. Electrocardiographic evidence of severe conduction system abnormalities OR
  4. New York Heart Association (NYHA) Class II - IV heart failure (Subjects with other cardiac abnormalities may be included if documented by the investigator as not clinically significant)
* Pregnant or nursing (lactating) women
* Enrolled in any other treatment study within 30 days of consent
* Serious medical illness (other than renal disease), or psychiatric illness likely to interfere with study participation

Primary outcomes:
measure: Difference in mean change from screening to 36 months in graft survival and glomerular filtration rates (GFR)
timeFrame: 3 years
Secondary outcomes:
measure: Allograft Survival
timeFrame: 3 years
Other outcomes:
measure: Allograft survival in subjects with preformed DSA defined as an MFI > 500 at the time of transplantation
timeFrame: 3 years
measure: Allograft survival in subjects who are recipients of >1 renal transplant
timeFrame: 3 years
measure: A difference in mean change of extended GFR ml/min/1.73 m2 (eGFR - MDRD)
timeFrame: 3 years
measure: Incidence of proteinuria (urine protein:creatinine > 1.5) at 1, 2 and 3 years
timeFrame: 3 years
measure: Change in proteinuria from screening to 1, 2, and 3 years
timeFrame: 3 years
measure: Change in serum creatinine from screening to 1, 2, and 3 years
timeFrame: 3 years
measure: Proportion of subjects that achieve a complete response defined as a return of DSAmax antibody MFI to less than 2000 at 9 months
timeFrame: 3 years
Locations:
city: Los Angeles
country: United States
facility: St Vincent's Transplant Research Institute
state: California
city: Sacramento
country: United States
facility: University of California Davis Health Systems
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Cornell Medical Center
state: New York
city: Fort Worth
country: United States
facility: Baylor Research Institute
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: A. O. Gaber, MD
role: PRINCIPAL_INVESTIGATOR
References: