IVIg to Treat BK Viremia in Kidney Transplant Recipients
Primary Purpose
Kidney Transplantation, BK Virus, Isoantibodies
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IVIg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Kidney Transplantation
Eligibility Criteria
Inclusion Criteria:
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of intravenous immune globulin, or agree to completely abstain from heterosexual intercourse.
- Kidney transplant recipients (living and deceased donors) with new onset BK viremia (defined as BKV plasma DNA load >1000 copies/mL by real-time PCR within 2 weeks of enrollment). For values >5000 copies/mL repeat testing is not required. For values ≤5000 copies/mL repeat testing should be performed to confirm viremia before enrollment.
- Immunosuppression therapy at enrollment with tacrolimus, MPA, +/- prednisone.
- Men and Women 18 to 75 years of age.
Exclusion Criteria:
- Absence of a DQ mismatch to the donor.
- Patient had known HLA antibodies directed to the donor antigens (pre-formed DSA) prior to transplant.
- Known to be positive for donor specific anti-HLA antibodies (IgG) at time of enrollment from the most recently drawn sample. (DSA MFI>1000 is considered positive). DSA is detected via center's standard of care testing. If center does not routinely screen then patient may still be enrolled.
- History of biopsy proven acute rejection (cellular or antibody) at any time prior to enrollment.
- BKV plasma DNA viral load >300,000 copies/ml.
- Patient who have received intravenous immune globulin for any reason within 1 month prior to enrollment.
- Patient with an estimated glomerular filtration rate (MDRD) ≤ 30 ml/min at time of study entry.
- Patient with selective IgA deficiency or have known antibodies to IgA.
- Patient with history of hyperprolinemia.
- Patient with a previous history of a severe systemic or anaphylactic response to intravenous immune globulin.
- Female subject is pregnant or lactating.
- Current HCV positivity (by PCR).
- History of HBsAg-positive.
- Patients who are HIV-positive.
- Recipients of a kidney from a donor who tests positive for HIV or HBsAg
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
- Inability to perform follow-up or to undergo renal allograft biopsy.
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Sites / Locations
- Beth Israel Deaconess Medical Center
- Massachusetts General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Group 1 (Treatment)
Group 2 (Control)
Arm Description
Intravenous immune globulin (IVIg; Privigen®) 1g/kg monthly for 2 months with immunosuppression reduction.
Placebo infusion monthly for 2 months with immunosuppression reduction
Outcomes
Primary Outcome Measures
BK Viremia
Resolution of BK viremia by 3 months post-enrollment. Resolution is defined as a decrease in viral load of BKV in the plasma to <1000 copies/mL.
Secondary Outcome Measures
Donor specific anti-HLA antibodies
Prevention of new donor specific anti-HLA antibodies (DSA)
Kidney graft survival
Acute Cellular Rejection
Incidence of acute cellular rejection (Banff 2013 Criteria)
BK Nephropathy
Proportion of BKV nephropathy
Acute Antibody Mediated Rejection
Incidence of acute antibody mediated rejection
Interstitial Fibrosis or Transplant Glomerulopathy
Incidence of interstitial fibrosis or transplant glomerulopathy
Glomerular Filtrition Rate (GFR)
Proportion of delta decline in estimated glomerular filtration rate (MDRD) of >20%
BKV remission
Length of BKV remission (time from clearance of BK viremia to reappearance of BK viremia (plasma DNA load >1000 copies/mL x 2 measures that are a 4weeks apart) or end of study
Full Information
NCT ID
NCT02659891
First Posted
January 14, 2016
Last Updated
September 2, 2021
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02659891
Brief Title
IVIg to Treat BK Viremia in Kidney Transplant Recipients
Official Title
Immunoglobulin (Privigen®) Therapy to Treat BK Viremia and Prevent Alloimmune Activation in Kidney Transplant Recipients
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
May 2016 (undefined)
Primary Completion Date
December 10, 2020 (Actual)
Study Completion Date
March 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
5. Study Description
Brief Summary
The overall goal of this study is to rapidly improve clearance of BK viremia with Immunoglobulin (Privigen®) thereby decreasing the potential for formation of alloantibodies in renal transplant recipients that have had immunosuppression reduction due to BK viremia. Our approach is to perform a prospective, randomized, placebo controlled trial intravenous immune globulin (IVIg; Privigen®) plus protocolized immunosuppression reduction versus placebo and protocolized immunosuppression reduction in patients with BK viremia post-kidney transplantation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Transplantation, BK Virus, Isoantibodies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 (Treatment)
Arm Type
Active Comparator
Arm Description
Intravenous immune globulin (IVIg; Privigen®) 1g/kg monthly for 2 months with immunosuppression reduction.
Arm Title
Group 2 (Control)
Arm Type
Placebo Comparator
Arm Description
Placebo infusion monthly for 2 months with immunosuppression reduction
Intervention Type
Biological
Intervention Name(s)
IVIg
Other Intervention Name(s)
Privigen®
Intervention Type
Other
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
BK Viremia
Description
Resolution of BK viremia by 3 months post-enrollment. Resolution is defined as a decrease in viral load of BKV in the plasma to <1000 copies/mL.
Time Frame
3 Months
Secondary Outcome Measure Information:
Title
Donor specific anti-HLA antibodies
Description
Prevention of new donor specific anti-HLA antibodies (DSA)
Time Frame
12 Months
Title
Kidney graft survival
Time Frame
12 Months
Title
Acute Cellular Rejection
Description
Incidence of acute cellular rejection (Banff 2013 Criteria)
Time Frame
12 Months
Title
BK Nephropathy
Description
Proportion of BKV nephropathy
Time Frame
12 Months
Title
Acute Antibody Mediated Rejection
Description
Incidence of acute antibody mediated rejection
Time Frame
12 Months
Title
Interstitial Fibrosis or Transplant Glomerulopathy
Description
Incidence of interstitial fibrosis or transplant glomerulopathy
Time Frame
12 Months
Title
Glomerular Filtrition Rate (GFR)
Description
Proportion of delta decline in estimated glomerular filtration rate (MDRD) of >20%
Time Frame
12 Months
Title
BKV remission
Description
Length of BKV remission (time from clearance of BK viremia to reappearance of BK viremia (plasma DNA load >1000 copies/mL x 2 measures that are a 4weeks apart) or end of study
Time Frame
Up to 24 Months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
Female subject is either postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of intravenous immune globulin, or agree to completely abstain from heterosexual intercourse.
Kidney transplant recipients (living and deceased donors) with new onset BK viremia (defined as BKV plasma DNA load >1000 copies/mL by real-time PCR within 2 weeks of enrollment). For values >5000 copies/mL repeat testing is not required. For values ≤5000 copies/mL repeat testing should be performed to confirm viremia before enrollment.
Immunosuppression therapy at enrollment with tacrolimus, MPA, +/- prednisone.
Men and Women 18 to 75 years of age.
Exclusion Criteria:
Absence of a DQ mismatch to the donor.
Patient had known HLA antibodies directed to the donor antigens (pre-formed DSA) prior to transplant.
Known to be positive for donor specific anti-HLA antibodies (IgG) at time of enrollment from the most recently drawn sample. (DSA MFI>1000 is considered positive). DSA is detected via center's standard of care testing. If center does not routinely screen then patient may still be enrolled.
History of biopsy proven acute rejection (cellular or antibody) at any time prior to enrollment.
BKV plasma DNA viral load >300,000 copies/ml.
Patient who have received intravenous immune globulin for any reason within 1 month prior to enrollment.
Patient with an estimated glomerular filtration rate (MDRD) ≤ 30 ml/min at time of study entry.
Patient with selective IgA deficiency or have known antibodies to IgA.
Patient with history of hyperprolinemia.
Patient with a previous history of a severe systemic or anaphylactic response to intravenous immune globulin.
Female subject is pregnant or lactating.
Current HCV positivity (by PCR).
History of HBsAg-positive.
Patients who are HIV-positive.
Recipients of a kidney from a donor who tests positive for HIV or HBsAg
Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
Inability to perform follow-up or to undergo renal allograft biopsy.
Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hannah Gilligan, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
12. IPD Sharing Statement
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IVIg to Treat BK Viremia in Kidney Transplant Recipients
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