IVIg to Treat BK Viremia in Kidney Transplant Recipients

Kidney Transplantation Clinical Trial

Official title:

Immunoglobulin (Privigen®) Therapy to Treat BK Viremia and Prevent Alloimmune Activation in Kidney Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02659891
• Other study ID #: 2016P000224
• Status: Completed
• Phase: Phase 1
• Start date: May 2016
• Est. completion date: March 31, 2021

Study information

• Verified date: September 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: March 31, 2021
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.

Related Conditions & MeSH terms

• BK Virus
• Isoantibodies
• Kidney Transplantation
• Viremia

Intervention

Biological:
• IVIg

Other:
• Placebo

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 Months
Secondary	Donor specific anti-HLA antibodies	Prevention of new donor specific anti-HLA antibodies (DSA)	12 Months
Secondary	Kidney graft survival		12 Months
Secondary	Acute Cellular Rejection	Incidence of acute cellular rejection (Banff 2013 Criteria)	12 Months
Secondary	BK Nephropathy	Proportion of BKV nephropathy	12 Months
Secondary	Acute Antibody Mediated Rejection	Incidence of acute antibody mediated rejection	12 Months
Secondary	Interstitial Fibrosis or Transplant Glomerulopathy	Incidence of interstitial fibrosis or transplant glomerulopathy	12 Months
Secondary	Glomerular Filtrition Rate (GFR)	Proportion of delta decline in estimated glomerular filtration rate (MDRD) of >20%	12 Months
Secondary	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	Up to 24 Months