IVIg to Treat BK Viremia in Kidney Transplant Recipients

• ClinicalTrials.gov Identifier: NCT02659891
• Recruitment Status: Active, not recruiting
• First Posted: January 21, 2016
• Last Update Posted: August 19, 2020
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Hannah Gilligan, Massachusetts General Hospital

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.

Condition or disease	Intervention/treatment	Phase
Kidney Transplantation; BK Virus; Isoantibodies	Biological: IVIg; Other: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Immunoglobulin (Privigen®) Therapy to Treat BK Viremia and Prevent Alloimmune Activation in Kidney Transplant Recipients
• Study Start Date: May 2016
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: February 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Group 1 (Treatment); Intravenous immune globulin (IVIg; Privigen®) 1g/kg monthly for 2 months with immunosuppression reduction.	Biological: IVIg; Other Name: Privigen®
Placebo Comparator: Group 2 (Control); Placebo infusion monthly for 2 months with immunosuppression reduction	Other: Placebo

Outcome Measures

Primary Outcome Measures :

1. BK Viremia [ Time Frame: 3 Months ]
   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 :

1. Donor specific anti-HLA antibodies [ Time Frame: 12 Months ]
   Prevention of new donor specific anti-HLA antibodies (DSA)
2. Kidney graft survival [ Time Frame: 12 Months ]
3. Acute Cellular Rejection [ Time Frame: 12 Months ]
   Incidence of acute cellular rejection (Banff 2013 Criteria)
4. BK Nephropathy [ Time Frame: 12 Months ]
   Proportion of BKV nephropathy
5. Acute Antibody Mediated Rejection [ Time Frame: 12 Months ]
   Incidence of acute antibody mediated rejection
6. Interstitial Fibrosis or Transplant Glomerulopathy [ Time Frame: 12 Months ]
   Incidence of interstitial fibrosis or transplant glomerulopathy
7. Glomerular Filtrition Rate (GFR) [ Time Frame: 12 Months ]
   Proportion of delta decline in estimated glomerular filtration rate (MDRD) of >20%
8. BKV remission [ Time Frame: Up to 24 Months ]
   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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Hannah Gilligan, MD; Massachusetts General Hospital

More Information

• Responsible Party: Hannah Gilligan, Transplant Nephrologist, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02659891
• Other Study ID Numbers: 2016P000224
• First Posted: January 21, 2016
• Last Update Posted: August 19, 2020
• Last Verified: August 2020

Additional relevant MeSH terms:

Viremia; Virus Diseases; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Immunoglobulins, Intravenous; Immunologic Factors; Physiological Effects of Drugs