Renal Transplants in Hepatitis C Negative Recipients With Nucleic Acid Positive Donors

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03627299
• Other study ID #: IRB00174409
• Status: Completed
• Phase: Phase 4
• Start date: September 25, 2018
• Est. completion date: September 20, 2021

Study information

• Verified date: September 2021
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 20, 2021
• Est. primary completion date: December 19, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Hepatitis
• Hepatitis A
• Hepatitis C
• Kidney Failure, Chronic

Intervention

Drug:
• 300mg glecaprevir/pibrentasivir 120mg
300mg glecaprevir/pibrentasivir 120mg 4 weeks post-transplant

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Viral Response at Week 12	This is the number of participants with undetectable hepatitis C RNA in the blood at 12 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 12	12 weeks after completing therapy
Primary	Number of Participants With Grade 3 or Higher Treatment-related Adverse Events Related to the Use of G-P	Proportion of participants with grade 3 or higher treatment-related adverse events (AE) as assessed by US Department of Health and Human Services Common Terminology of AEs version 4. An AE is an unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5. Grade 3 Severe or medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. The investigator will determine if the AE is related to the treatment.	4 weeks after transplant
Secondary	Viral Response at 1 Week	This is the number of participants with undetectable hepatitis C RNA in the blood at 1 week after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 1	1 week after completing therapy
Secondary	Viral Response at 2 Weeks	This is the number of participants with undetectable hepatitis C RNA in the blood at 2 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 2	2 weeks after completing therapy
Secondary	Viral Response at 4 Weeks	This is the number of participants with undetectable hepatitis C RNA in the blood at 4 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 4	4 weeks after completing therapy
Secondary	Viral Response at 8 Weeks	This is the number of participants with undetectable hepatitis C RNA in the blood at 8 weeks after stopping treatment. Proportion of kidney transplant recipients with HCV RNA < Lower Limit Of Quantification (LLOQ) at week 8	8 weeks after completing therapy
Secondary	Antibody Development	Number of kidney transplant recipients that become reactive for HCV antibody	week 12 after discontinuation of therapy
Secondary	T-cell Response at Baseline	Measurement of t-cell response to HCV peptides, a marker of acute hepatitis C infection. This categorizes participants into no T-cell response, T-cell response to 1 peptide, T-cell response to 2 peptides and T-cell response to 3 peptides.	Baseline prior to induction therapy
Secondary	T-cell Response at 12 Weeks	Measurement of t-cell response to HCV peptides, a marker of acute hepatitis C infection. This categorizes participants into no T-cell response, T-cell response to 1 peptide, T-cell response to 2 peptides and T-cell response to 3 peptides.	Week12 after discontinuation of therapy
Secondary	Kidney Function at 6 Months	Serum creatinine mg/dL at 6 months following transplantation	6 months following transplant
Secondary	Kidney Function at 12 Months	Serum creatinine mg/dL at 12 months following transplantation	12 months following transplant