Clinical trial NCT03627299: Renal Transplants in Hepatitis C Negative Recipients With Nucleic Acid Positive Donors
Official title: An Open-label Pilot Study to Determine the Safety and Efficacy of Fixed-dose Glecaprevir and Pibrentasvir Treatment in Hepatitis C Uninfected Recipients of Renal Transplants From Hepatitis C Infected Deceased Donors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: End Stage Renal Disease
Hepatitis C
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2018-08-13
Enrollment: 11
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include glecaprevir 300 mg / pibrentasvir 120 mg (G-P) administered on-call to the operating room for the renal transplant procedure and continued for 4 weeks post-renal transplant.

Detailed description: In this study, individuals without hepatitis C infection who are on the kidney transplant waitlist will receive a kidney from a deceased donor with hepatitis C infection and will be treated for hepatitis C at the same time. Treatment will include glecaprevir 300 mg / pibrentasvir 120 mg (G-P) administered on-call to the operating room for the renal transplant procedure and continued for 4 weeks post-renal transplant. The participant will continue to be tested for Hepatitis C for 12 weeks post-treatment.

The primary hypothesis is that prophylactic treatment with glecaprevir/pibrentasvir before and after transplant will prevent the establishment of HCV infection in the recipients of kidneys from HCV-infected deceased donors. Based on the success of preliminary studies, the objective of the study is to evaluate the safety and efficacy of 4 weeks of G-P as prophylaxis for HCV D+/R- kidney transplant.

Eligibility criteria: Recipient Inclusion Criteria

* Participants ≥ 40 years old
* On the deceased donor kidney waitlist at Johns Hopkins Hospital
* Awaiting a first or second kidney transplant
* No available living kidney donors
* On hemodialysis or peritoneal dialysis or stage 5 chronic kidney disease defined as a glomerular filtration rate \<15 ml/min for ≥ past 90 days
* HCV-uninfected (by both antibody and RNA PCR) and without any behavioral risk factors for contracting HCV other than being on hemodialysis
* Calculated panel reactive anti-human leukocyte antigen antibody (cPRA) below 80%

Recipient Exclusion Criteria

* Plan to receive a multi-organ transplant
* Plan to receive a dual kidney transplant (including en bloc)
* Prior solid organ transplant
* Participating in another study that involves an intervention or investigational product
* Plan to receive a blood type incompatible kidney
* History of human immunodeficiency (HIV), hepatitis C (HCV), or active hepatitis B (HBV) infection, defined as being on active antiviral treatment for HBV, detectable hepatitis B surface Ag or detectable hepatitis B DNA
* Unable to safely substitute or discontinue a medication that is contraindicated with the study medication
* Psychiatric or physical illness that in the opinion of the investigator would make it unsafe to proceed with transplantation or interfere with the ability of the subject to participate in the study

Primary outcomes:
measure: Viral Response at Week 12
timeFrame: 12 weeks after completing therapy
measure: Number of Participants With Grade 3 or Higher Treatment-related Adverse Events Related to the Use of G-P
timeFrame: 4 weeks after transplant
Secondary outcomes:
measure: Viral Response at 1 Week
timeFrame: 1 week after completing therapy
measure: Viral Response at 2 Weeks
timeFrame: 2 weeks after completing therapy
measure: Viral Response at 4 Weeks
timeFrame: 4 weeks after completing therapy
measure: Viral Response at 8 Weeks
timeFrame: 8 weeks after completing therapy
measure: Antibody Development
timeFrame: week 12 after discontinuation of therapy
measure: T-cell Response at Baseline
timeFrame: Baseline prior to induction therapy
measure: T-cell Response at 12 Weeks
timeFrame: Week12 after discontinuation of therapy
measure: Kidney Function at 6 Months
timeFrame: 6 months following transplant
measure: Kidney Function at 12 Months
timeFrame: 12 months following transplant
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Christine Durand, MD
role: PRINCIPAL_INVESTIGATOR
References: