Clinical trial NCT02659891: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Transplantation
BK Virus
Isoantibodies
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-01-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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

Primary outcomes:
measure: BK Viremia
timeFrame: 3 Months
Secondary outcomes:
measure: Donor specific anti-HLA antibodies
timeFrame: 12 Months
measure: Kidney graft survival
timeFrame: 12 Months
measure: Acute Cellular Rejection
timeFrame: 12 Months
measure: BK Nephropathy
timeFrame: 12 Months
measure: Acute Antibody Mediated Rejection
timeFrame: 12 Months
measure: Interstitial Fibrosis or Transplant Glomerulopathy
timeFrame: 12 Months
measure: Glomerular Filtrition Rate (GFR)
timeFrame: 12 Months
measure: BKV remission
timeFrame: Up to 24 Months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Hannah Gilligan, MD
role: PRINCIPAL_INVESTIGATOR
References: