A Prospective, Global, Multi-center, Treatment Registry Study of Intravenous Immunoglobulin Maintenance Therapy in Alloantibody Positive Renal Allograft Recipients

NCT02115503 | Terminated DMC

• 1 other identifier: DSA 3242014
• Study Type: observational
• Target: 52
• Locations: 1 country
• Sites: 8

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.

Conditions

Renal Transplant Recipients With Anti-HLA Antibodies

Outcome Measures

Primary Outcomes (1)

• Difference in mean change from screening to 36 months in graft survival and glomerular filtration rates (GFR)

  Success is defined as: Allograft survival as compared to the performance goal (PG) at 36 months. For the purposes of this study, a graft will be presumed to be lost is when a subject is started on dialysis and is not able to subsequently be removed from dialysis; or a subject's serum creatinine reaches 4.0 mg/dL, is sustained for \>48hours and is not thought to be due to other causes; or the subject is re-transplanted; or the subject dies. AND: A change in extended GFR, defined as \<15% decrease in mean GFR from baseline to 36 months

  3 years

Secondary Outcomes (1)

• Allograft Survival

  3 years

Other Outcomes (7)

• Allograft survival in subjects with preformed DSA defined as an MFI > 500 at the time of transplantation

  3 years

• Allograft survival in subjects who are recipients of >1 renal transplant

  3 years

• A difference in mean change of extended GFR ml/min/1.73 m2 (eGFR - MDRD)

  3 years

Study Arms (3)

Cohort 1

Cohort 1 will consist of those having primarily Class I antibody development post-transplant

Cohort 2

Cohort 2 will include those having primarily Class II antibody development post-transplant

Cohort 3

Cohort 3 will consist of the remaining subjects that have a mix of Class I and II antibodies.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Primary care clinic

You may qualify if:

• 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

You may not qualify if:

• 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:
• Biopsy proven acute Cellular Rejection \[Banff grade I (including IA and IB), grade II (including IIA and IIB) or grade III\]; or
• an antibody-mediated rejection with C4d positivity, or
• 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.

Sponsors & Collaborators

• Databean: lead
• Octapharma: collaborator

Study Sites (8)

St Vincent's Transplant Research Institute

Los Angeles, California, 90057, United States

Location

University of California Davis Health Systems

Sacramento, California, 95817, United States

Location

University of Colorado, Denver

Aurora, Colorado, 80045, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Cornell Medical Center

New York, New York, 10021, United States

Location

Baylor Research Institute

Fort Worth, Texas, 76104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Study Officials

• A. O. Gaber, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2014
• First Posted: April 16, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2019
• Study Completion: April 1, 2020
• Last Updated: February 20, 2024

Record last verified: 2024-02

Locations

US (8)